Transduplication resulted in the incorporation of two protein-coding sequences into the Turmoil-1 transposable element of C. elegans

Transposable elements may acquire unrelated gene fragments into their sequences in a process called transduplication. Transduplication of protein-coding genes is common in plants, but is unknown of in animals. Here, we report that the Turmoil-1 transposable element in C. elegans has incorporated two protein-coding sequences into its inverted terminal repeat (ITR) sequences. The ITRs of Turmoil-1 contain a conserved RNA recognition motif (RRM) that originated from the rsp- 2 gene and a fragment from the protein-coding region of the cpg-3 gene. We further report that an open reading frame specific to C. elegans may have been created as a result of a Turmoil-1 insertion. Mutations at the 5' splice site of this open reading frame may have reactivated the transduplicated RRM moti

Selecton 2007: advanced models for detecting positive and purifying selection using a Bayesian inference approach

Biologically significant sites in a protein may be identified by contrasting the rates of synonymous (Ks) and non-synonymous (Ka) substitutions. This enables the inference of site-specific positive Darwinian selection and purifying selection. We present here Selecton version 2.2 (http://selecton.bioinfo.tau.ac.il), a web server which automatically calculates the ratio between Ka and Ks (ω) at each site of the protein. This ratio is graphically displayed on each site using a color-coding scheme, indicating either positive selection, purifying selection or lack of selection. Selecton implements an assembly of different evolutionary models, which allow for statistical testing of the hypothesis that a protein has undergone positive selection. Specifically, the recently developed mechanistic-empirical model is introduced, which takes into account the physicochemical properties of amino acids. Advanced options were introduced to allow maximal fine tuning of the server to the user's specific needs, including calculation of statistical support of the ω values, an advanced graphic display of the protein's 3-dimensional structure, use of different genetic codes and inputting of a pre-built phylogenetic tree. Selecton version 2.2 is an effective, user-friendly and freely available web server which implements up-to-date methods for computing site-specific selection forces, and the visualization of these forces on the protein's sequence and structure

Strongly aligned gas-phase molecules at Free-Electron Lasers

We demonstrate a novel experimental implementation to strongly align molecules at full repetition rates of free-electron lasers. We utilized the available in-house laser system at the coherent x-ray imaging beamline at the Linac Coherent Light Source. Chirped laser pulses, i. e., the direct output from the regenerative amplifier of the Ti:Sa chirped pulse amplification laser system, were used to strongly align 2,5-diiodothiophene molecules in a molecular beam. The alignment laser pulses had pulse energies of a few mJ and a pulse duration of 94 ps. A degree of alignment of \left = 0.85 was measured, limited by the intrinsic temperature of the molecular beam rather than by the available laser system. With the general availability of synchronized chirped-pulse-amplified near-infrared laser systems at short-wavelength laser facilities, our approach allows for the universal preparation of molecules tightly fixed in space for experiments with x-ray pulses.Comment: 10 pages, 5 figure

Testing for Home Team and Favorite Biases in the Australian Rules Football Fixed-Odds and Point Spread Betting Markets

In this paper, we test two different kinds of bias; the favorite-longshot/favorite-underdog and the home team bias, and distinguish between the two, using a distinctive feature of the Australian Football League (AFL), that many games are played on neutral grounds. This is the first empirical study, to the best of our knowledge, to make a clear distinction between the two types of bias. We conduct our tests by subjecting 2001-2004 data for the AFL to detailed scrutiny, using standard econometric weak-form efficiency models of point spread and fixed odds betting markets. Where the results suggest the presence of a bias, we test potential profitability via betting simulation. We are able to reject the existence of any significant pure favorite-longshot/favorite-underdog bias in either market, and to demonstrate the existence of a significant bias in favor of teams with an apparent home ground advantage in games played outside Victoria in the point spread market and in the fixed odds market during 2002, 2004 and the period as a whole. Games in Melbourne and in Geelong are free of such a bias (except for 2003 in the point spread market in Geelong). Betting simulations which attempt to exploit these inefficiencies yield modest profits

Synonymous site conservation in the HIV-1 genome

Background: Synonymous or silent mutations are usually thought to evolve neutrally. However, accumulating recent evidence has demonstrated that silent mutations may destabilize RNA structures or disrupt cis regulatory motifs superimposed on coding sequences. Such observations suggest the existence of stretches of codon sites that are evolutionary conserved at both DNA-RNA and protein levels. Such stretches may point to functionally important regions within protein coding sequences not necessarily reflecting functional constraints on the amino-acid sequence. The HIV-1 genome is highly compact, and often harbors overlapping functional elements at the protein, RNA, and DNA levels. This superimposition of functions leads to complex selective forces acting on all levels of the genome and proteome. Considering the constraints on HIV-1 to maintain such a highly compact genome, we hypothesized that stretches of synonymous conservation would be common within its genome. Results: We used a combined computational-experimental approach to detect and characterize regions exhibiting strong purifying selection against synonymous substitutions along the HIV-1 genome. Our methodology is based on advanced probabilistic evolutionary models that explicitly account for synonymous rate variation among sites and rate dependencies among adjacent sites. These models are combined with a randomization procedure to automatically identify the most statistically significant regions of conserved synonymous sites along the genome. Using this procedure we identified 21 conserved regions. Twelve of these are mapped to regions within overlapping genes, seven correlate with known functional elements, while the functions of the remaining four are yet unknown. Among these four regions, we chose the one that deviates most from synonymous rate homogeneity for in-depth computational and experimental characterization. In our assays aiming to quantify viral fitness in both early and late stages of the replication cycle, no differences were observed between the mutated and the wild type virus following the introduction of synonymous mutations. Conclusions: The contradiction between the inferred purifying selective forces and the lack of effect of these mutations on viral replication may be explained by the fact that the phenotype was measured in single-cycle infection assays in cell culture. Such a system does not account for the complexity of HIV-1 infections in vivo, which involves multiple infection cycles and interaction with the host immune system

Dual array EEG-fMRI : An approach for motion artifact suppression in EEG recorded simultaneously with fMRI

Objective: Although simultaneous recording of EEG and MRI has gained increasing popularity in recent years, the extent of its clinical use remains limited by various technical challenges. Motion interference is one of the major challenges in EEG-fMRI. Here we present an approach which reduces its impact with the aid of an MR compatible dual-array EEG (daEEG) in which the EEG itself is used both as a brain signal recorder and a motion sensor. Methods: We implemented two arrays of EEG electrodes organized into two sets of nearly orthogonally intersecting wire bundles. The EEG was recorded using referential amplifiers inside a 3 T MR-scanner. Virtual bipolar measurements were taken both along bundles (creating a small wire loop and therefore minimizing artifact) and across bundles (creating a large wire loop and therefore maximizing artifact). Independent component analysis (ICA) was applied. The resulting ICA components were classified into brain signal and noise using three criteria: 1) degree of two-dimensional spatial correlation between ICA coefficients along bundles and across bundles; 2) amplitude along bundles vs. across bundles; 3) correlation with ECG. The components which passed the criteria set were transformed back to the channel space. Motion artifact suppression and the ability to detect interictal epileptic spikes following daEEG and Optimal Basis Set (OBS) procedures were compared in 10 patients with epilepsy. Results: The SNR achieved by daEEG was 11.05 +/- 3.10 and by OBS was 8.25 +/- 1.01 (p <0.00001). In 9 of 10 patients, more spikes were detected after daEEG than after OBS (p <0.05). Significance: daEEG improves signal quality in EEG-fMRI recordings, expanding its clinical and research potential. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Evaluation of a Simple, Scalable, Parallel Best-First Search Strategy

Large-scale, parallel clusters composed of commodity processors are increasingly available, enabling the use of vast processing capabilities and distributed RAM to solve hard search problems. We investigate Hash-Distributed A* (HDA*), a simple approach to parallel best-first search that asynchronously distributes and schedules work among processors based on a hash function of the search state. We use this approach to parallelize the A* algorithm in an optimal sequential version of the Fast Downward planner, as well as a 24-puzzle solver. The scaling behavior of HDA* is evaluated experimentally on a shared memory, multicore machine with 8 cores, a cluster of commodity machines using up to 64 cores, and large-scale high-performance clusters, using up to 2400 processors. We show that this approach scales well, allowing the effective utilization of large amounts of distributed memory to optimally solve problems which require terabytes of RAM. We also compare HDA* to Transposition-table Driven Scheduling (TDS), a hash-based parallelization of IDA*, and show that, in planning, HDA* significantly outperforms TDS. A simple hybrid which combines HDA* and TDS to exploit strengths of both algorithms is proposed and evaluated.Comment: in press, to appear in Artificial Intelligenc

Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication

Viruses are known for their extremely compact genomes composed almost entirely of protein-coding genes. Nonetheless, four long noncoding RNAs (lncRNAs) are encoded by human cytomegalovirus (HCMV). Although these RNAs accumulate to high levels during lytic infection, their functions remain largely unknown. Here, we show that HCMV-encoded lncRNA4.9 localizes to the viral nuclear replication compartment, and that its depletion restricts viral DNA replication and viral growth. RNA4.9 is transcribed from the HCMV origin of replication (oriLyt) and forms an RNA-DNA hybrid (R-loop) through its G+C-rich 5’ end, which may be important for the initiation of viral DNA replication. Furthermore, targeting the RNA4.9 promoter with CRISPR-Cas9 or genetic relocalization of oriLyt leads to reduced levels of the viral single-stranded DNA-binding protein (ssDBP), suggesting that the levels of ssDBP are coupled to the oriLyt activity. We further identified a similar, oriLyt-embedded, G+C-rich lncRNA in murine cytomegalovirus (MCMV). These results indicate that HCMV RNA4.9 plays an important role in regulating viral DNA replication, that the levels of ssDBP are coupled to the oriLyt activity, and that these regulatory features may be conserved among betaherpesviruses

X-ray diffractive imaging of controlled gas-phase molecules: Toward imaging of dynamics in the molecular frame

We report experimental results on the diffractive imaging of three-dimensionally aligned 2,5-diiodothiophene molecules. The molecules were aligned by chirped near-infrared laser pulses, and their structure was probed at a photon energy of 9.5 keV ($\lambda\approx130 \text{pm}$) provided by the Linac Coherent Light Source. Diffracted photons were recorded on the CSPAD detector and a two-dimensional diffraction pattern of the equilibrium structure of 2,5-diiodothiophene was recorded. The retrieved distance between the two iodine atoms agrees with the quantum-chemically calculated molecular structure to within 5 %. The experimental approach allows for the imaging of intrinsic molecular dynamics in the molecular frame, albeit this requires more experimental data which should be readily available at upcoming high-repetition-rate facilities