Role of noncoding RNA in vascular remodelling

Purpose of review: Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are becoming fundamentally important in the pathophysiology relating to injury-induced vascular remodelling. We highlight recent studies that demonstrate the involvement of ncRNAs in vein graft disease, in in-stent restenosis and in pulmonary arterial hypertension, with a particular focus on endothelial cell and vascular smooth muscle cell function. We also briefly discuss the emerging role of exosomal-derived ncRNAs and how this mechanism impacts on vascular function. Recent findings: ncRNAs have been described as novel regulators in the pathophysiology of vascular injury, inflammation, and vessel wall remodelling. In particular, several studies have demonstrated that manipulation of miRNAs can reduce the burden of pathological vascular remodelling. Such studies have also shown that exosomal miRNA-mediated, cell-to-cell communication between endothelial cells and vascular smooth muscle cells is critical in the disease process. In addition to miRNAs, lncRNAs are emerging as regulators of vascular function in health and disease. Although lncRNAs are complex in both their sheer numbers and mechanisms of action, identifying their contribution to vascular disease is essential. Summary: Given the important roles of ncRNAs in vascular injury and remodelling together will their capacity for cell-to-cell communication, manipulating ncRNA might provide novel therapeutic interventions

Finite amplitude propagation of focused ultrasonic waves in water

SIGLEAvailable from British Library Document Supply Centre- DSC:DX88719 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

ALMA Observations of Circumnuclear Disks in Early Type Galaxies: 12CO(2-1) and Continuum Properties

We present results from an Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 2 program to map CO(2-1) emission in nearby early-type galaxies (ETGs) that host circumnuclear gas disks. We obtained $\sim0.3''-$resolution Band 6 observations of seven ETGs selected on the basis of dust disks in Hubble Space Telescope images. We detect CO emission in five at high signal-to-noise ratio with the remaining two only faintly detected. All CO emission is coincident with the dust and is in dynamically cold rotation. Four ETGs show evidence of rapid central rotation; these are prime candidates for higher-resolution ALMA observations to measure the black hole masses. In this paper we focus on the molecular gas and continuum properties. Total gas masses and H$_2$ column densities for our five CO-bright galaxies are on average $\sim10^8$ $M_\odot$ and $\sim10^{22.5}$ cm$^{-2}$ over the $\sim$kpc-scale disks, and analysis suggests that these disks are stabilized against gravitational fragmentation. The continuum emission of all seven galaxies is dominated by a central, unresolved source, and in five we also detect a spatially extended component. The $\sim$230 GHz nuclear continua are modeled as power laws ranging from $S_\nu \sim \nu^{-0.4}$ to $\nu^{1.6}$ within the observed frequency band. The extended continuum profiles of the two radio-bright (and CO-faint) galaxies are roughly aligned with their radio jet and suggests resolved synchrotron jets. The extended continua of the CO-bright disks are coincident with optically thick dust absorption and have spectral slopes that are consistent with thermal dust emission.Comment: 20 pages, 10 figures; accepted for publication in Ap

The Jenolan Environmental Monitoring Program

The Jenolan Environmental Monitoring Program reports on the condition of atmospheric and water parameters in and around the show caves at Jenolan. This paper summarises the key findings from four years (2009-2012) of monitoring cave atmosphere. The caves were typically characterised by high relative humidity, moderately stable air temperature (annual variatio

Genomic analysis of Xenopus organizer function

BACKGROUND: Studies of the Xenopus organizer have laid the foundation for our understanding of the conserved signaling pathways that pattern vertebrate embryos during gastrulation. The two primary activities of the organizer, BMP and Wnt inhibition, can regulate a spectrum of genes that pattern essentially all aspects of the embryo during gastrulation. As our knowledge of organizer signaling grows, it is imperative that we begin knitting together our gene-level knowledge into genome-level signaling models. The goal of this paper was to identify complete lists of genes regulated by different aspects of organizer signaling, thereby providing a deeper understanding of the genomic mechanisms that underlie these complex and fundamental signaling events. RESULTS: To this end, we ectopically overexpress Noggin and Dkk-1, inhibitors of the BMP and Wnt pathways, respectively, within ventral tissues. After isolating embryonic ventral halves at early and late gastrulation, we analyze the transcriptional response to these molecules within the generated ectopic organizers using oligonucleotide microarrays. An efficient statistical analysis scheme, combined with a new Gene Ontology biological process annotation of the Xenopus genome, allows reliable and faithful clustering of molecules based upon their roles during gastrulation. From this data, we identify new organizer-related expression patterns for 19 genes. Moreover, our data sub-divides organizer genes into separate head and trunk organizing groups, which each show distinct responses to Noggin and Dkk-1 activity during gastrulation. CONCLUSION: Our data provides a genomic view of the cohorts of genes that respond to Noggin and Dkk-1 activity, allowing us to separate the role of each in organizer function. These patterns demonstrate a model where BMP inhibition plays a largely inductive role during early developmental stages, thereby initiating the suites of genes needed to pattern dorsal tissues. Meanwhile, Wnt inhibition acts later during gastrulation, and is essential for maintenance of organizer gene expression throughout gastrulation, a role which may depend on its ability to block the expression of a host of ventral, posterior, and lateral fate-specifying factors

An electrostatic mechanism for Ca(2+)-mediated regulation of gap junction channels.

Gap junction channels mediate intercellular signalling that is crucial in tissue development, homeostasis and pathologic states such as cardiac arrhythmias, cancer and trauma. To explore the mechanism by which Ca(2+) blocks intercellular communication during tissue injury, we determined the X-ray crystal structures of the human Cx26 gap junction channel with and without bound Ca(2+). The two structures were nearly identical, ruling out both a large-scale structural change and a local steric constriction of the pore. Ca(2+) coordination sites reside at the interfaces between adjacent subunits, near the entrance to the extracellular gap, where local, side chain conformational rearrangements enable Ca(2+)chelation. Computational analysis revealed that Ca(2+)-binding generates a positive electrostatic barrier that substantially inhibits permeation of cations such as K(+) into the pore. Our results provide structural evidence for a unique mechanism of channel regulation: ionic conduction block via an electrostatic barrier rather than steric occlusion of the channel pore