SIGGMA: A Survey of Ionized Gas in the Galaxy, Made with the Arecibo Telescope

A Survey of Ionized Gas in the Galaxy, made with the Arecibo telescope (SIGGMA) uses the Arecibo L-band Feed Array (ALFA) to fully sample the Galactic plane (30 < l < 75 and -2 < b < 2; 175 < l < 207 and -2 < b < 1) observable with the telescope in radio recombination lines (RRLs). Processed data sets are being produced in the form of data cubes of 2 degree (along l) x 4 degree (along b) x 151 (number of channels), archived and made public. The 151 channels cover a velocity range of 600 km/s and the velocity resolution of the survey changes from 4.2 km/s to 5.1 km/s from the lowest frequency channel to the highest frequency channel, respectively.RRL maps with 3.4 arcmin resolution and line flux density sensitivity of 0.5 mJy will enable us to identify new HII regions, measure their electron temperatures, study the physics of photodissociation regions (PDRs) with carbon RRLs, and investigate the origin of the extended low density medium (ELDM). Twelve Hn{\alpha} lines fall within the 300 MHz bandpass of ALFA; they are resampled to a common velocity resolution to improve the signal-to-noise ratio (SN) by a factor of 3 or more and preserve the line width. SIGGMA will produce the most sensitive fully sampled RRL survey to date. Here we discuss the observing and data reduction techniques in detail. A test observation toward the HII region complex S255/S257 has detected Hn{\alpha} and Cn{\alpha} lines with SN>10

Planetary Nebulae as Probes of Stellar Evolution and Populations

Planetary Nebulae (PNe) have been used satisfactory to test the effects of stellar evolution on the Galactic chemical environment. Moreover, a link exists between nebular morphology and stellar populations and evolution. We present the latest results on Galactic PN morphology, and an extension to a distance unbiased and homogeneous sample of Large Magellanic Cloud PNe. We show that PNe and their morphology may be successfully used as probes of stellar evolution and populations.Comment: to appear in: Chemical Evolution of the Milky Way: stars versus clusters, ed. F. Giovannelli and F. Matteucci, Kluwer (2000), in pres

The post-AGB evolution of AGB mass loss variations

We present new numerical hydrodynamical modelling of the evolution of Asymptotic Giant Branch (AGB) mass loss fluctuations during the post-AGB/Planetary Nebula phase. These models show that after ionization, the observable effects of the mass loss fluctuations disappear in a few thousand years, consistent with the fact that only few PNe have been found to be surrounded by `rings'. We derive the observational characteristics of these rings, and compare them to reported observations of the rings around NGC 6543, finding a good match of emission properties and line shapes. We predict small variations in the observable electron temperatures.Comment: 12 pages, 13 figures, accepted by A&

A search for periodicity in the light curves of selected blazars

We present an analysis of multifrequency light curves of the sources 2223-052 (3C 446), 2230+114 (CTA 102), and 2251+158 (3C 454.3), which had shown evidence of quasi-periodic activity. The analysis made use of data from the University of Michican Radio Astronomy Observatory (USA) at 4.8, 8, and 14.5 GHz, as well as the Metsahovi Radio Astronomy Observatory (Finland) at 22 and 37 GHz. Application of two different methods (the discrete autocorrelation function and the method of Jurkevich) both revealed evidence for periodicity in the flux variations of these sources at essentially all frequencies. The periods derived for at least two of the sources -- 2223-052 and 2251+158-- are in good agreement with the time interval between the appearance of successive VLBI components. The derived periods for 2251+158 (P = 12.4 yr and 2223-052 (P = 5.8 yr) coincide with the periods found earlier by other authors based on optical light curves.Comment: 27 pages, 11 figures, accepted for publication in Astronomy Report

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

Intermediate and extreme mass-ratio inspirals — astrophysics, science applications and detection using LISA

Black hole binaries with extreme (gtrsim104:1) or intermediate (~102–104:1) mass ratios are among the most interesting gravitational wave sources that are expected to be detected by the proposed laser interferometer space antenna (LISA). These sources have the potential to tell us much about astrophysics, but are also of unique importance for testing aspects of the general theory of relativity in the strong field regime. Here we discuss these sources from the perspectives of astrophysics, data analysis and applications to testing general relativity, providing both a description of the current state of knowledge and an outline of some of the outstanding questions that still need to be addressed. This review grew out of discussions at a workshop in September 2006 hosted by the Albert Einstein Institute in Golm, Germany

Defects in muscarinic receptor-coupled signal transduction in isolated parotid gland cells after in vivo irradiation: evidence for a non-DNA target of radiation

Radiation-induced dysfunction of normal tissue, an unwanted side effect of radiotherapeutic treatment of cancer, is usually considered to be caused by impaired loss of cell renewal due to sterilisation of stem cells. This implies that the onset of normal tissue damage is usually determined by tissue turnover rate. Salivary glands are a clear exception to this rule: they have slow turnover rates (>60 days), yet develop radiation-induced dysfunction within hours to days. We showed that this could not be explained by a hypersensitivity to radiation-induced apoptosis or necrosis of the differentiated cells. In fact, salivary cells are still capable of amylase secretion shortly after irradiation while at the same time water secretion seems specifically and severely impaired. Here, we demonstrate that salivary gland cells isolated after in vivo irradiation are impaired in their ability to mobilise calcium from intracellular stores (Ca2+i), the driving force for water secretion, after exposure to muscarinic acetylcholine receptor agonists. Using radioligand-receptor-binding assays it is shown that radiation caused no changes in receptor density, receptor affinity nor in receptor-G-protein coupling. However, muscarinic acetylcholine agonist-induced activation of protein kinase C alpha (PKCα), measured as translocation to the plasma membrane, was severely affected in irradiated cells. Also, the phorbol ester PMA could no longer induce PKCα translocation in irradiated cells. Our data hence indicate that irradiation specifically interferes with PKCα association with membranes, leading to impairment of intracellular signalling. To the best of our knowledge, these data for the first time suggest that, the cells' capacity to respond to a receptor agonist is impaired after irradiation

DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway

Stabilization of mutant p53 (mutp53) in tumours greatly contributes to malignant progression. However, little is known about the underlying mechanisms and therapeutic approaches to destabilize mutp53. Here, through high-throughput screening we identify statins, cholesterol-lowering drugs, as degradation inducers for conformational or misfolded p53 mutants with minimal effects on wild-type p53 (wtp53) and DNA contact mutants. Statins preferentially suppress mutp53-expressing cancer cell growth. Specific reduction of mevalonate-5-phosphate by statins or mevalonate kinase knockdown induces CHIP ubiquitin ligase-mediated nuclear export, ubiquitylation, and degradation of mutp53 by impairing interaction of mutp53 with DNAJA1, a Hsp40 family member. Knockdown of DNAJA1 also induces CHIP-mediated mutp53 degradation, while its overexpression antagonizes statin-induced mutp53 degradation. Our study reveals that DNAJA1 controls the fate of misfolded mutp53, provides insights into potential strategies to deplete mutp53 through the mevalonate pathway–DNAJA1 axis, and highlights the significance of p53 status in impacting statins’ efficacy on cancer therapy

High-Level Expression of Wild-Type p53 in Melanoma Cells is Frequently Associated with Inactivity in p53 Reporter Gene Assays

Background: Inactivation of the p53 pathway that controls cell cycle progression, apoptosis and senescence, has been proposed to occur in virtually all human tumors and p53 is the protein most frequently mutated in human cancer. However, the mutational status of p53 in melanoma is still controversial; to clarify this notion we analysed the largest series of melanoma samples reported to date. Methodology/Principal Findings: Immunohistochemical analysis of more than 180 melanoma specimens demonstrated that high levels of p53 are expressed in the vast majority of cases. Subsequent sequencing of the p53 exons 5–8, however, revealed only in one case the presence of a mutation. Nevertheless, by means of two different p53 reporter constructs we demonstrate transcriptional inactivity of wild type p53 in 6 out of 10 melanoma cell lines; the 4 other p53 wild type melanoma cell lines exhibit p53 reporter gene activity, which can be blocked by shRNA knock down of p53. Conclusions/Significance: In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level

Evolution of the Primate APOBEC3A Cytidine Deaminase Gene and Identification of Related Coding Regions

The APOBEC3 gene cluster encodes six cytidine deaminases (A3A-C, A3DE, A3F-H) with single stranded DNA (ssDNA) substrate specificity. For the moment A3A is the only enzyme that can initiate catabolism of both mitochondrial and nuclear DNA. Human A3A expression is initiated from two different methionine codons M1 or M13, both of which are in adequate but sub-optimal Kozak environments. In the present study, we have analyzed the genetic diversity among A3A genes across a wide range of 12 primates including New World monkeys, Old World monkeys and Hominids. Sequence variation was observed in exons 1–4 in all primates with up to 31% overall amino acid variation. Importantly for 3 hominids codon M1 was mutated to a threonine codon or valine codon, while for 5/12 primates strong Kozak M1 or M13 codons were found. Positive selection was apparent along a few branches which differed compared to positive selection in the carboxy-terminal of A3G that clusters with A3A among human cytidine deaminases. In the course of analyses, two novel non-functional A3A-related fragments were identified on chromosome 4 and 8 kb upstream of the A3 locus. This qualitative and quantitative variation among primate A3A genes suggest that subtle differences in function might ensue as more light is shed on this increasingly important enzyme