Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

Extragalactic Results from the Infrared Space Observatory

More than a decade ago the IRAS satellite opened the realm of external galaxies for studies in the 10 to 100 micron band and discovered emission from tens of thousands of normal and active galaxies. With the 1995-1998 mission of the Infrared Space Observatory the next major steps in extragalactic infrared astronomy became possible: detailed imaging, spectroscopy and spectro-photometry of many galaxies detected by IRAS, as well as deep surveys in the mid- and far- IR. The spectroscopic data reveal a wealth of detail about the nature of the energy source(s) and about the physical conditions in galaxies. ISO's surveys for the first time explore the infrared emission of distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is the role of star formation in the activity and evolution of galaxies.Comment: 106 pages, including 17 figures. Ann.Rev.Astron.Astrophys. (in press), a gzip'd pdf file (667kB) is also available at http://www.mpe.mpg.de/www_ir/preprint/annrev2000.pdf.g

Estimating Impact Forces of Tail Club Strikes by Ankylosaurid Dinosaurs

BACKGROUND: It has been assumed that the unusual tail club of ankylosaurid dinosaurs was used actively as a weapon, but the biological feasibility of this behaviour has not been examined in detail. Ankylosaurid tail clubs are composed of interlocking vertebrae, which form the handle, and large terminal osteoderms, which form the knob. METHODOLOGY/PRINCIPAL FINDINGS: Computed tomographic (CT) scans of several ankylosaurid tail clubs referred to Dyoplosaurus and Euoplocephalus, combined with measurements of free caudal vertebrae, provide information used to estimate the impact force of tail clubs of various sizes. Ankylosaurid tails are modeled as a series of segments for which mass, muscle cross-sectional area, torque, and angular acceleration are calculated. Free caudal vertebrae segments had limited vertical flexibility, but the tail could have swung through approximately 100 degrees laterally. Muscle scars on the pelvis record the presence of a large M. longissimus caudae, and ossified tendons alongside the handle represent M. spinalis. CT scans showed that knob osteoderms were predominantly cancellous, which would have lowered the rotational inertia of the tail club and made it easier to wield as a weapon. CONCLUSIONS/SIGNIFICANCE: Large knobs could generate sufficient force to break bone during impacts, but average and small knobs could not. Tail swinging behaviour is feasible in ankylosaurids, but it remains unknown whether the tail was used for interspecific defense, intraspecific combat, or both

The effectiveness of tobacco control television advertisements in increasing the prevalence of smoke-free homes

BACKGROUND: There is considerable evidence that tobacco control mass media campaigns can change smoking behaviour. In the UK, campaigns over the last decade have contributed to declines in smoking prevalence and been associated with falls in cigarette consumption among continuing smokers. However, it is less evident whether such campaigns can also play a role in changing smokers’ behaviour in relation to protecting others from the harmful effects of their smoking in the home. We investigated whether exposure to English televised tobacco control campaigns, and specifically campaigns targeting second hand smoking, is associated with smokers having a smoke-free home. METHODS: We used repeated cross-sectional national survey data on 9872 households which participated in the Health Survey for England between 2004 and 2010, with at least one adult current smoker living in the household. Exposure to all government-funded televised tobacco control campaigns, and to those specifically with a second hand smoking theme, was quantified in Gross Rating Points (GRPs), an average per capita measure of advert exposure where 100 GRPs indicates 100 % of adults exposed once or 50 % twice. Our outcome was self-reported presence of a smoke-free home (where no one smokes in the home on most days). Analysis used generalised additive models, controlling for individual factors and temporal trends. RESULTS: There was no association between monthly televised campaigns overall and the probability of having a smoke-free home. However, exposure to campaigns specifically targeting second hand smoke was associated with increased odds of a smoke-free home in the following month (odds ratio per additional 100 GRPs, 1.07, 95 % CI 1.01 to 1.13), though this association was not seen at other lags. These effects were not modified by socio-economic status or by presence of a child in the home. CONCLUSIONS: Our findings provide tentative evidence that mass media campaigns specifically focussing on second hand smoke may be effective in reducing smoking in the home, and further evaluation of campaigns of this type is needed. General tobacco control campaigns in England, which largely focus on promoting smoking cessation, do not impact on smoke-free homes over and above their direct effect at reducing smoking

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Spatial and Seasonal Distribution of American Whaling and Whales in the Age of Sail

American whalemen sailed out of ports on the east coast of the United States and in California from the 18th to early 20th centuries, searching for whales throughout the world’s oceans. From an initial focus on sperm whales (Physeter macrocephalus) and right whales (Eubalaena spp.), the array of targeted whales expanded to include bowhead whales (Balaena mysticetus), humpback whales (Megaptera novaeangliae), and gray whales (Eschrichtius robustus). Extensive records of American whaling in the form of daily entries in whaling voyage logbooks contain a great deal of information about where and when the whalemen found whales. We plotted daily locations where the several species of whales were observed, both those caught and those sighted but not caught, on world maps to illustrate the spatial and temporal distribution of both American whaling activity and the whales. The patterns shown on the maps provide the basis for various inferences concerning the historical distribution of the target whales prior to and during this episode of global whaling

Maximum-Entropy Weighting of Multi-Component Earth Climate Models

A maximum entropy-based framework is presented for the synthesis of projections from multiple Earth climate models. This identifies the most representative (most probable) model from a set of climate models -- as defined by specified constraints -- eliminating the need to calculate the entire set. Two approaches are developed, based on individual climate models or ensembles of models, subject to a single cost (energy) constraint or competing cost-benefit constraints. A finite-time limit on the minimum cost of modifying a model synthesis framework, at finite rates of change, is also reported.Comment: Inspired by discussions at the Mathematical and Statistical Approaches to Climate Modelling and Prediction workshop, Isaac Newton Institute for Mathematical Sciences, Cambridge, UK, 11 Aug. to 22 Dec. 2010. Accepted for publication in Climate Dynamics, 8 August 201

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

Controlling the Outcome of the Toll-Like Receptor Signaling Pathways

The Toll-Like Receptors (TLRs) are proteins involved in the immune system that increase cytokine levels when triggered. While cytokines coordinate the response to infection, they appear to be detrimental to the host when reaching too high levels. Several studies have shown that the deletion of specific TLRs was beneficial for the host, as cytokine levels were decreased consequently. It is not clear, however, how targeting other components of the TLR pathways can improve the responses to infections. We applied the concept of Minimal Cut Sets (MCS) to the ihsTLR v1.0 model of the TLR pathways to determine sets of reactions whose knockouts disrupt these pathways. We decomposed the TLR network into 34 modules and determined signatures for each MCS, i.e. the list of targeted modules. We uncovered 2,669 MCS organized in 68 signatures. Very few MCS targeted directly the TLRs, indicating that they may not be efficient targets for controlling these pathways. We mapped the species of the TLR network to genes in human and mouse, and determined more than 10,000 Essential Gene Sets (EGS). Each EGS provides genes whose deletion suppresses the network's outputs