Debris Disks: Probing Planet Formation

Debris disks are the dust disks found around ~20% of nearby main sequence stars in far-IR surveys. They can be considered as descendants of protoplanetary disks or components of planetary systems, providing valuable information on circumstellar disk evolution and the outcome of planet formation. The debris disk population can be explained by the steady collisional erosion of planetesimal belts; population models constrain where (10-100au) and in what quantity (>1Mearth) planetesimals (>10km in size) typically form in protoplanetary disks. Gas is now seen long into the debris disk phase. Some of this is secondary implying planetesimals have a Solar System comet-like composition, but some systems may retain primordial gas. Ongoing planet formation processes are invoked for some debris disks, such as the continued growth of dwarf planets in an unstirred disk, or the growth of terrestrial planets through giant impacts. Planets imprint structure on debris disks in many ways; images of gaps, clumps, warps, eccentricities and other disk asymmetries, are readily explained by planets at >>5au. Hot dust in the region planets are commonly found (<5au) is seen for a growing number of stars. This dust usually originates in an outer belt (e.g., from exocomets), although an asteroid belt or recent collision is sometimes inferred.Comment: Invited review, accepted for publication in the 'Handbook of Exoplanets', eds. H.J. Deeg and J.A. Belmonte, Springer (2018

Assessment of Virally Vectored Autoimmunity as a Biocontrol Strategy for Cane Toads

BACKGROUND: The cane toad, Bufo (Chaunus) marinus, is one of the most notorious vertebrate pests introduced into Australia over the last 200 years and, so far, efforts to identify a naturally occurring B. marinus-specific pathogen for use as a biological control agent have been unsuccessful. We explored an alternative approach that entailed genetically modifying a pathogen with broad host specificity so that it no longer caused disease, but carried a gene to disrupt the cane toad life cycle in a species specific manner. METHODOLOGY/PRINCIPAL FINDINGS: The adult beta globin gene was selected as the model gene for proof of concept of autoimmunity as a biocontrol method for cane toads. A previous report showed injection of bullfrog tadpoles with adult beta globin resulted in an alteration in the form of beta globin expressed in metamorphs as well as reduced survival. In B. marinus we established for the first time that the switch from tadpole to adult globin exists. The effect of injecting B. marinus tadpoles with purified recombinant adult globin protein was then assessed using behavioural (swim speed in tadpoles and jump length in metamorphs), developmental (time to metamorphosis, weight and length at various developmental stages, protein profile of adult globin) and genetic (adult globin mRNA levels) measures. However, we were unable to detect any differences between treated and control animals. Further, globin delivery using Bohle iridovirus, an Australian ranavirus isolate belonging to the Iridovirus family, did not reduce the survival of metamorphs or alter the form of beta globin expressed in metamorphs. CONCLUSIONS/SIGNIFICANCE: While we were able to show for the first time that the switch from tadpole to adult globin does occur in B. marinus, we were not able to induce autoimmunity and disrupt metamorphosis. The short development time of B. marinus tadpoles may preclude this approach

Visualizing spatially correlated dynamics that directs RNA conformational transitions

RNAs fold into three- dimensional ( 3D) structures that subsequently undergo large, functionally important, conformational transitions in response to a variety of cellular signals(1-3). RNA structures are believed to encode spatially tuned flexibility that can direct transitions along specific conformational pathways(4,5). However, this hypothesis has proved difficult to examine directly because atomic movements in complex biomolecules cannot be visualized in 3D by using current experimental methods. Here we report the successful implementation of a strategy using NMR that has allowed us to visualize, with complete 3D rotational sensitivity, the dynamics between two RNA helices that are linked by a functionally important trinucleotide bulge over timescales extending up to milliseconds. The key to our approach is to anchor NMR frames of reference onto each helix and thereby directly measure their dynamics, one relative to the other, using 'relativistic' sets of residual dipolar couplings ( RDCs)(6,7). Using this approach, we uncovered super- large amplitude helix motions that trace out a surprisingly structured and spatially correlated 3D dynamic trajectory. The two helices twist around their individual axes by approximately 536 and 1106 in a highly correlated manner ( R = 0.97) while simultaneously ( R = 0.81 - 0.92) bending by about 94 degrees. Remarkably, the 3D dynamic trajectory is dotted at various positions by seven distinct ligand- bound conformations of the RNA. Thus even partly unstructured RNAs can undergo structured dynamics that directs ligand- induced transitions along specific predefined conformational pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62506/1/nature06389.pd

Overlay of conventional angiographic and en-face OCT images enhances their interpretation

BACKGROUND: Combining characteristic morphological and functional information in one image increases pathophysiologic understanding as well as diagnostic accuracy in most clinical settings. En-face optical coherence tomography (OCT) provides a high resolution, transversal OCT image of the macular area combined with a confocal image of the same area (OCT C-scans). Creating an overlay image of a conventional angiographic image onto an OCT image, using the confocal part to facilitate transformation, combines structural and functional information of the retinal area of interest. This paper describes the construction of such overlay images and their aid in improving the interpretation of OCT C-scans. METHODS: In various patients, en-face OCT C-scans (made with a prototype OCT-Ophthalmoscope (OTI, Canada) in use at the Department of Ophthalmology (Academic Medical Centre, Amsterdam, The Netherlands)) and conventional fluorescein angiography (FA) were performed. ImagePro, with a custom made plug-in, was used to make an overlay-image. The confocal part of the OCT C-scan was used to spatially transform the FA image onto the OCT C-scan, using the vascular arcades as a reference. To facilitate visualization the transformed angiographic image and the OCT C-scan were combined in an RGB image. RESULTS: The confocal part of the OCT C-scan could easily be fused with angiographic images. Overlay showed a direct correspondence between retinal thickening and FA leakage in Birdshot retinochoroiditis, localized the subretinal neovascular membrane and correlated anatomic and vascular leakage features in myopia, and showed the extent of retinal and pigment epithelial detachment in retinal angiomatous proliferation as FA leakage was subject to blocked fluorescence. The overlay mode provided additional insight not readily available in either mode alone. CONCLUSION: Combining conventional angiographic images and en-face OCT C-scans assists in the interpretation of both imaging modalities. By combining the physiopathological information in the angiograms with the structural information in the OCT scan, zones of leakage can be correlated to structural changes in the retina or pigment epithelium. This strategy could be used in the evaluation and monitoring of patients with complex central macular pathology

Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial

Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaig

Simulation of developmental changes in action potentials with ventricular cell models

During cardiomyocyte development, early embryonic ventricular cells show spontaneous activity that disappears at a later stage. Dramatic changes in action potential are mediated by developmental changes in individual ionic currents. Hence, reconstruction of the individual ionic currents into an integrated mathematical model would lead to a better understanding of cardiomyocyte development. To simulate the action potential of the rodent ventricular cell at three representative developmental stages, quantitative changes in the ionic currents, pumps, exchangers, and sarcoplasmic reticulum (SR) Ca2+ kinetics were represented as relative activities, which were multiplied by conductance or conversion factors for individual ionic systems. The simulated action potential of the early embryonic ventricular cell model exhibited spontaneous activity, which ceased in the simulated action potential of the late embryonic and neonatal ventricular cell models. The simulations with our models were able to reproduce action potentials that were consistent with the reported characteristics of the cells in vitro. The action potential of rodent ventricular cells at different developmental stages can be reproduced with common sets of mathematical equations by multiplying conductance or conversion factors for ionic currents, pumps, exchangers, and SR Ca2+ kinetics by relative activities

Selective Phosphorylation Modulates the PIP2 Sensitivity of the CaM-SK Channel Complex

Phosphatidylinositol bisphosphate (PIP2) regulates the activities of many membrane proteins including ion channels through direct interactions. However, the affinity of PIP2 is so high for some channel proteins that its physiological role as a modulator has been questioned. Here we show that PIP2 is an important cofactor for activation of small conductance Ca2+-activated potassium channels (SK) by Ca2+-bound calmodulin (CaM). Removal of the endogenous PIP2 inhibits SK channels. The PIP2-binding site resides at the interface of CaM and the SK C-terminus. We further demonstrate that the affinity of PIP2 for its target proteins can be regulated by cellular signaling. Phosphorylation of CaM T79, located adjacent to the PIP2-binding site, by Casein Kinase 2 reduces the affinity of PIP2 for the CaM-SK channel complex by altering the dynamic interactions among amino acid residues surrounding the PIP2-binding site. This effect of CaM phosphorylation promotes greater channel inhibition by G-protein-mediated hydrolysis of PIP2

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Mental health in the aged: prevalence, covariates and related neuroendocrine, cardiovascular and inflammatory factors of successful aging

<p>Abstract</p> <p>Background</p> <p>Although aging is accompanied by diminished functioning, many elderly individuals preserve a sense of well-being. While the concept of "successful aging" has been popular for many decades, little is known about its psycho-physiologic and endocrine underpinnings. KORA-Age is a population-based, longitudinal study designed to determine the prevalence of successfully aged men and women between 65 and 94 years old in the MONICA/KORA Augsburg cohort of randomly selected inhabitants. Specifically, we aim to identify predictors of successful aging and to elucidate bio-psychosocial mechanisms that maintain mental health and successful adaptation despite adverse experiences of life and aging.</p> <p>Methods/Design</p> <p>Components of successful aging were assessed in a telephone survey of 4,127 participants (2008-2009) enrolled in the MONICA/KORA cohort, on average, 13 years earlier. Psychosocial, somatic and behavioural predictors are used to determine factors that contribute to successful aging. An age-stratified random sub-sample (n = 1,079) participated in a personal interview where further psychological mechanisms that may underlie successful adaptation (resilience, social support, attachment) were examined. The interactions among neuroendocrine systems in the aging process are investigated by studying the cortisol/dehydroepiandrosterone-sulfate ratio, the level of insulin-like growth factor I, and oxytocin.</p> <p>Discussion</p> <p>Longitudinal determinants of successful aging can be assessed based on a follow-up of an average of 13 years. A comprehensive analysis of biological as well as physio-psychological information provides a unique opportunity to investigate relevant outcomes such as resilience and frailty in the elderly population.</p