Transcriptional slippage in bacteria: distribution in sequenced genomes and utilization in IS element gene expression

BACKGROUND: Transcription slippage occurs on certain patterns of repeat mononucleotides, resulting in synthesis of a heterogeneous population of mRNAs. Individual mRNA molecules within this population differ in the number of nucleotides they contain that are not specified by the template. When transcriptional slippage occurs in a coding sequence, translation of the resulting mRNAs yields more than one protein product. Except where the products of the resulting mRNAs have distinct functions, transcription slippage occurring in a coding region is expected to be disadvantageous. This probably leads to selection against most slippage-prone sequences in coding regions. RESULTS: To find a length at which such selection is evident, we analyzed the distribution of repetitive runs of A and T of different lengths in 108 bacterial genomes. This length varies significantly among different bacteria, but in a large proportion of available genomes corresponds to nine nucleotides. Comparative sequence analysis of these genomes was used to identify occurrences of 9A and 9T transcriptional slippage-prone sequences used for gene expression. CONCLUSIONS: IS element genes are the largest group found to exploit this phenomenon. A number of genes with disrupted open reading frames (ORFs) have slippage-prone sequences at which transcriptional slippage would result in uninterrupted ORF restoration at the mRNA level. The ability of such genes to encode functional full-length protein products brings into question their annotation as pseudogenes and in these cases is pertinent to the significance of the term 'authentic frameshift' frequently assigned to such genes

The only known cyclopygid–‘atheloptic’ trilobite fauna from North America: the upper Ordovician fauna of the Pyle Mountain Argillite and its palaeoenvironmental significance

The trilobite fauna of the upper Ordovician (middle Katian) Pyle Mountain Argillite comprises a mixture of abundant mesopelagic cyclopygids and other pelagic taxa and a benthic fauna dominated by trilobites lacking eyes. Such faunas were widespread in deep water environments around Gondwana and terranes derived from that continent throughout Ordovician time but this is the only known record of such a fauna from North America and thus from Laurentia. It probably reflects a major sea level rise (the ‘Linearis drowning events’) as does the development of coeval cyclopygid-dominated deep water trilobite faunas in terranes that were marginal to Laurentia and are now preserved in Ireland and Scotland. The Pyle Mountain Argillite trilobite fauna occurs with a deep water Foliomena brachiopod fauna and comprises 22 species. Pelagic trilobites (mostly cyclopygids) constitute 36% of the preserved sclerites, and 45% of the fauna is the remains of trilobites lacking eyes, including one new species, Dindymene whittingtoni sp. nov. Three species of cyclopygid are present, belonging in Cyclopyge, Symphysops and Microparia (Heterocyclopyge). Cyclopygids are widely thought to have been stratified in the water column in life and thus their taxonomic diversity reflects the relative depths of the sea-beds on which their remains accumulated. A tabulation of middle and upper Katian cyclopygid-bearing faunas from several palaeoplates and terranes arranged on the basis of increasing numbers of cyclopygid genera allows an assessment of the relative depth ranges of the associated benthic taxa. The Pyle Mountain Argillite fauna lies towards the deeper end of this depth spectrum

Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis

Essential biological systems employ self-correcting mechanisms to maintain cellular homeostasis. Mammalian cell function is dynamically regulated by the interaction of cell surface galectins with branched N-glycans. Here we report that N-glycan branching deficiency triggers the Golgi to generate bioequivalent N-glycans that preserve galectin-glycoprotein interactions and cellular homeostasis. Galectins bind N-acetyllactosamine (LacNAc) units within N-glycans initiated from UDP-GlcNAc by the medial-Golgi branching enzymes as well as the trans-Golgi poly-LacNAc extension enzyme β1,3-N-acetylglucosaminyltransferase (B3GNT). Marginally reducing LacNAc content by limiting N-glycans to three branches results in T-cell hyperactivity and autoimmunity; yet further restricting branching does not produce a more hyperactive state. Rather, new poly-LacNAc extension by B3GNT maintains galectin binding and immune homeostasis. Poly-LacNAc extension is triggered by redistribution of unused UDP-GlcNAc from the medial to trans-Golgi via inter-cisternal tubules. These data demonstrate the functional equivalency of structurally dissimilar N-glycans and suggest a self-correcting feature of the Golgi that sustains cellular homeostasis

A Search for Multi-Planet Systems Using the Hobby-Eberly Telescope

Extrasolar multiple-planet systems provide valuable opportunities for testing theories of planet formation and evolution. The architectures of the known multiple-planet systems demonstrate a fascinating level of diversity, which motivates the search for additional examples of such systems in order to better constrain their formation and dynamical histories. Here we describe a comprehensive investigation of 22 planetary systems in an effort to answer three questions: 1) Are there additional planets? 2) Where could additional planets reside in stable orbits? and 3) What limits can these observations place on such objects? We find no evidence for additional bodies in any of these systems; indeed, these new data do not support three previously announced planets (HD 20367b: Udry et al. 2003, HD 74156d: Bean et al. 2008, and 47 UMa c: Fischer et al. 2002). The dynamical simulations show that nearly all of the 22 systems have large regions in which additional planets could exist in stable orbits. The detection-limit computations indicate that this study is sensitive to close-in Neptune-mass planets for most of the systems targeted. We conclude with a discussion on the implications of these non-detections.Comment: Accepted to ApJS. Includes 39 pages of radial-velocity data table

Improving localization accuracy for non-invasive automated early left ventricular origin localization approach

Background: We previously developed a non-invasive approach to localize the site of early left ventricular activation origin in real time using 12-lead ECG, and to project the predicted site onto a generic LV endocardial surface using the smallest angle between two vectors algorithm (SA).Objectives: To improve the localization accuracy of the non-invasive approach by utilizing the K-nearest neighbors algorithm (KNN) to reduce projection errors.Methods: Two datasets were used. Dataset #1 had 1012 LV endocardial pacing sites with known coordinates on the generic LV surface and corresponding ECGs, while dataset #2 included 25 clinically-identified VT exit sites and corresponding ECGs. The non-invasive approach used “population” regression coefficients to predict the target coordinates of a pacing site or VT exit site from the initial 120-m QRS integrals of the pacing site/VT ECG. The predicted site coordinates were then projected onto the generic LV surface using either the KNN or SA projection algorithm.Results: The non-invasive approach using the KNN had a significantly lower mean localization error than the SA in both dataset #1 (9.4 vs. 12.5 mm, p < 0.05) and dataset #2 (7.2 vs. 9.5 mm, p < 0.05). The bootstrap method with 1,000 trials confirmed that using KNN had significantly higher predictive accuracy than using the SA in the bootstrap assessment with the left-out sample (p < 0.05).Conclusion: The KNN significantly reduces the projection error and improves the localization accuracy of the non-invasive approach, which shows promise as a tool to identify the site of origin of ventricular arrhythmia in non-invasive clinical modalities

Trajectory outlier detection: Algorithms, taxonomies, evaluation, and open challenges

acceptedVersio

The California Planet Survey III. A Possible 2:1 Resonance in the Exoplanetary Triple System HD 37124

We present new radial velocities from Keck Observatory and both Newtonian and Keplerian solutions for the triple-planet system orbiting HD 37124. The orbital solution for this system has improved dramatically since the third planet was first reported in Vogt et al. 2005 with an ambiguous orbital period. We have resolved this ambiguity, and the outer two planets have an apparent period commensurability of 2:1. A dynamical analysis finds both resonant and non-resonant configurations consistent with the radial velocity data, and constrains the mutual inclinations of the planets to be less than about 30 degrees. We discuss HD 37124 in the context of the other 19 exoplanetary systems with apparent period commenserabilities, which we summarize in a table. We show that roughly one in three well-characterized multiplanet systems has a apparent low-order period commensuribility, which is more than would naively be expected if the periods of exoplanets in known multiplanet systems were drawn randomly from the observed distribution of planetary orbital periods.Comment: 12 pp, emulateapj style, ApJ accepted. v2. Minor edits to update numbers, fix garbled tex

Putative tumour-suppressor gene DAB2 is frequently down regulated by promoter hypermethylation in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Human Disabled-2 (DAB2), is a multi-function signalling molecule that it is frequently down-regulated in human cancers. We aimed to investigate the possible tumour suppressor effect of DAB2 in nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>We studied the expression of DAB2 in NPC cell lines, xenografts and primary tumour samples. The status of promoter methylation was assessed by methylation specific PCR and bisulfite sequencing. The functional role of DAB2 in NPC was investigated by re-introducing DAB2 expression into NPC cell line C666-1.</p> <p>Results</p> <p>Decrease or absent of <it>DAB2 </it>transcript was observed in NPC cell lines and xenografts. Loss of DAB2 protein expression was seen in 72% (33/46) of primary NPC as demonstrated by immunohistochemistry. Aberrant <it>DAB2 </it>promoter methylation was detected in 65.2% (30/46) of primary NPC samples by methylation specific PCR. Treatment of the DAB2 negative NPC cell line C666-1 with 5-aza-2'-deoxycytidine resulted in restoration of DAB2 expression in a dose-dependent manner. Overexpression of DAB2 in NPC cell line C666-1 resulted in reduced growth rate and 35% reduction in anchorage-dependent colony formation, and inhibition of serum-induced c-Fos expression compared to vector-transfected controls. Over expression of DAB2 resulted in alterations of multiple pathways as demonstrated by expression profiling and functional network analysis, which confirmed the role of DAB2 as an adaptor molecule involved in multiple receptor-mediated signalling pathways.</p> <p>Conclusions</p> <p>We report the frequent down regulation of DAB2 in NPC and the promoter hypermethylation contributes to the loss of expression of DAB2. This is the first study demonstrating frequent DAB2 promoter hypermethylation in human cancer. Our functional studies support the putative tumour suppressor effect of DAB2 in NPC cells.</p

Stationary Black Holes: Uniqueness and Beyond

The spectrum of known black-hole solutions to the stationary Einstein equations has been steadily increasing, sometimes in unexpected ways. In particular, it has turned out that not all black-hole-equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro-vacuum black-hole spacetimes ceases to exist in self-gravitating non-linear field theories. This text aims to review some developments in the subject and to discuss them in light of the uniqueness theorem for the Einstein-Maxwell system.Comment: Major update of the original version by Markus Heusler from 1998. Piotr T. Chru\'sciel and Jo\~ao Lopes Costa succeeded to this review's authorship. Significantly restructured and updated all sections; changes are too numerous to be usefully described here. The number of references increased from 186 to 32