Gene finding in the chicken genome

Background: Despite the continuous production of genome sequence for a number of organisms,reliable, comprehensive, and cost effective gene prediction remains problematic. This is particularlytrue for genomes for which there is not a large collection of known gene sequences, such as therecently published chicken genome. We used the chicken sequence to test comparative andhomology-based gene-finding methods followed by experimental validation as an effective genomeannotation method.Results: We performed experimental evaluation by RT-PCR of three different computational genefinders, Ensembl, SGP2 and TWINSCAN, applied to the chicken genome. A Venn diagram wascomputed and each component of it was evaluated. The results showed that de novo comparativemethods can identify up to about 700 chicken genes with no previous evidence of expression, andcan correctly extend about 40% of homology-based predictions at the 5' end.Conclusions: De novo comparative gene prediction followed by experimental verification iseffective at enhancing the annotation of the newly sequenced genomes provided by standardhomology-based methods.

Conserved chromosomal clustering of genes governed by chromatin regulators in Drosophila

BACKGROUND: The trithorax group (trxG) and Polycomb group (PcG) proteins are responsible for the maintenance of stable transcriptional patterns of many developmental regulators. They bind to specific regions of DNA and direct the post-translational modifications of histones, playing a role in the dynamics of chromatin structure. RESULTS: We have performed genome-wide expression studies of trx and ash2 mutants in Drosophila melanogaster. Using computational analysis of our microarray data, we have identified 25 clusters of genes potentially regulated by TRX. Most of these clusters consist of genes that encode structural proteins involved in cuticle formation. This organization appears to be a distinctive feature of the regulatory networks of TRX and other chromatin regulators, since we have observed the same arrangement in clusters after experiments performed with ASH2, as well as in experiments performed by others with NURF, dMyc, and ASH1. We have also found many of these clusters to be significantly conserved in D. simulans, D. yakuba, D. pseudoobscura and partially in Anopheles gambiae. CONCLUSION: The analysis of genes governed by chromatin regulators has led to the identification of clusters of functionally related genes conserved in other insect species, suggesting this chromosomal organization is biologically important. Moreover, our results indicate that TRX and other chromatin regulators may act globally on chromatin domains that contain transcriptionally co-regulated genes.

Transcription factor map alignment of promoter regions

We address the problem of comparing and characterizing the promoter regions of genes with similar expression patterns. This remains a challenging problem in sequence analysis, because often the promoter regions of co-expressed genes do not show discernible sequence conservation. In our approach, thus, we have not directly compared the nucleotide sequence of promoters. Instead, we have obtained predictions of transcription factor binding sites, annotated the predicted sites with the labels of the corresponding binding factors, and aligned the resulting sequences of labels—to which we refer here as transcription factor maps (TF-maps). To obtain the global pairwise alignment of two TF-maps, we have adapted an algorithm initially developed to align restriction enzyme maps. We have optimized the parameters of the algorithm in a small, but well-curated, collection of human–mouse orthologous gene pairs. Results in this dataset, as well as in an independent much larger dataset from the CISRED database, indicate that TF-map alignments are able to uncover conserved regulatory elements, which cannot be detected by the typical sequence alignments.

Genome-wide screen of genes required for caffeine tolerance in fission yeast

Background: An excess of caffeine is cytotoxic to all eukaryotic cell types. We aim to study how cells become tolerant to atoxic dose of this drug, and the relationship between caffeine and oxidative stress pathways.Methodology/Principal Findings: We searched for Schizosaccharomyces pombe mutants with inhibited growth on caffeinecontainingplates. We screened a collection of 2,700 haploid mutant cells, of which 98 were sensitive to caffeine. The genes mutated in these sensitive clones were involved in a number of cellular roles including the H2O2-induced Pap1 and Sty1 stress pathways, the integrity and calcineurin pathways, cell morphology and chromatin remodeling. We have investigated the role of the oxidative stress pathways in sensing and promoting survival to caffeine. The Pap1 and the Sty1 pathways are both required for normal tolerance to caffeine, but only the Sty1 pathway is activated by the drug. Cells lacking Pap1 aresensitive to caffeine due to the decreased expression of the efflux pump Hba2. Indeed, ?hba2 cells are sensitive to caffeine, and constitutive activation of the Pap1 pathway enhances resistance to caffeine in an Hba2-dependent manner. Conclusions/Significance: With our caffeine-sensitive, genome-wide screen of an S. pombe deletion collection, we havedemonstrated the importance of some oxidative stress pathway components on wild-type tolerance to the drug.

THC prevents MDMA neurotoxicity in mice

The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg ×4) were pretreated with THC (3 mg/kg ×4) at room (21°C) and at warm (26°C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB1 receptor antagonist AM251 and the CB2 receptor antagonist AM630, as well as in CB1, CB2 and CB1/CB2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB1 receptor antagonist AM251, neither in CB1 and CB1/CB2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB2 cannabinoid antagonist and in CB2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB1 receptor, although CB2 receptors may also contribute to attenuate neuroinflammation in this process.

Cardiac injuries in blunt chest trauma

Blunt chest traumas are a clinical challenge, both for diagnosis and treatment. The use ofCardiovascular Magnetic Resonance can play a major role in this setting. We present two cases: a12-year-old boy and 45-year-old man. Late gadolinium enhancement imaging enabled visualizationof myocardial damage resulting from the trauma.

The role of computational fluid dynamics in the management of unruptured intracranial aneurysms: a clinicians' view

Objective: The importance of hemodynamics in the etiopathogenesis of intracranial aneurysms (IAs) is widely accepted.Computational fluid dynamics (CFD) is being used increasingly for hemodynamic predictions. However, alogn with thecontinuing development and validation of these tools, it is imperative to collect the opinion of the clinicians. Methods: A workshopon CFD was conducted during the European Society of Minimally Invasive Neurological Therapy (ESMINT) Teaching Course,Lisbon, Portugal. 36 delegates, mostly clinicians, performed supervised CFD analysis for an IA, using the @neuFuse softwaredeveloped within the European project @neurIST. Feedback on the workshop was collected and analyzed. The performancewas assessed on a scale of 1 to 4 and, compared with experts’ performance. Results: Current dilemmas in the management ofunruptured IAs remained the most important motivating factor to attend the workshop and majority of participants showedinterest in participating in a multicentric trial. The participants achieved an average score of 2.52 (range 0–4) which was 63% (range 0–100%) of an expert user. Conclusions: Although participants showed a manifest interest in CFD, there was a clear lack ofawareness concerning the role of hemodynamics in the etiopathogenesis of IAs and the use of CFD in this context. More effortstherefore are required to enhance understanding of the clinicians in the subject.

A WiMAX-based implementation of network MIMO for indoor wireless systems

It is well known that multiple-input multiple-output (MIMO) techniques can bring numerous benefits, such as higher spectral efficiency, to point-to-point wireless links. More recently, there has been interest in extending MIMO concepts tomultiuser wireless systems. Our focus in this paper is on network MIMO, a family of techniques whereby each end user in a wireless access network is served through several access points within its range of influence. By tightly coordinating the transmission and reception of signals at multiple access points, network MIMO can transcend the limits on spectral efficiency imposed by cochannel interference. Taking prior information-theoretic analyses of networkMIMO to the next level, we quantify the spectral efficiency gains obtainable under realistic propagation and operational conditions in a typical indoor deployment. Our study relies on detailed simulations and, for specificity, is conducted largely within the physical-layer framework of the IEEE 802.16e Mobile WiMAX system. Furthermore,to facilitate the coordination between access points, we assume that a high-capacity local area network, such as Gigabit Ethernet,connects all the access points. Our results confirm that network MIMO stands to provide a multiple-fold increase in spectralefficiency under these conditions.

A two-stage approach for tonic identification in indian art music

In this paper we propose a new approach for tonic identification in Indian art music and present a proposal for acomplete iterative system for the same. Our method splits the task of tonic pitch identification into two stages. In the first stage, which is applicable to both vocal and instrumental music, we perform a multi-pitch analysis of the audio signal to identify the tonic pitch-class. Multi-pitch analysisallows us to take advantage of the drone sound, which constantlyreinforces the tonic. In the second stage we estimate the octave in which the tonic of the singer lies and is thusneeded only for the vocal performances. We analyse the predominant melody sung by the lead performer in order to establish the tonic octave. Both stages are individually evaluated on a sizable music collection and are shown toobtain a good accuracy. We also discuss the types of errors made by the method.Further, we present a proposal for a system that aims to incrementally utilize all the available data, both audio and metadata in order to identify the tonic pitch. It produces a tonic estimate and a confidence value, and is iterative in nature. At each iteration, more data is fed into the systemuntil the confidence value for the identified tonic is above a defined threshold. Rather than obtain high overall accuracy for our complete database, ultimately our goal is to develop a system which obtains very high accuracy on a subset of the database with maximum confidence.

A method for extracting semantic information from on-line art music discussion forums

In this paper a method for extracting semantic informationfrom online music discussion forums is proposed. The semantic relations are inferred from the co-occurrence of musical concepts in forum posts, using network analysis. The method starts by defining a dictionary of common music terms in an art music tradition. Then, it creates a complex network representation of the online forum by matchingsuch dictionary against the forum posts. Once the complex network is built we can study different network measures, including node relevance, node co-occurrence andterm relations via semantically connecting words. Moreover, we can detect communities of concepts inside the forum posts. The rationale is that some music terms are more related to each other than to other terms. All in all, this methodology allows us to obtain meaningful and relevantinformation from forum discussions.

Analysis of the folksonomy of freesound

User generated content shared in online communities is often described using collaborative tagging systems where users assign labels to content resources. As a result, a folksonomy emerges that relates a number of tags with the resources they label and the users that have used them. In this paper we analyze the folksonomy of Freesound, an online audio clip sharing site which contains more than two million users and 150,000 user-contributed sound samplescovering a wide variety of sounds. By following methodologies taken from similar studies, we compute some metrics that characterize the folksonomy both at the globallevel and at the tag level. In this manner, we are able to betterunderstand the behavior of the folksonomy as a whole, and also obtain some indicators that can be used as metadata for describing tags themselves. We expect that such a methodology for characterizing folksonomies can be useful to support processes such as tag recommendation or automatic annotation of online resources.

Characterization of intonation in Karṇāṭaka music by parametrizing context-based Svara Distributions

Intonation is a fundamental music concept that has a special relevance in Indian art music. It is characteristic of the rāga and intrinsic to the musical expression of the performer. Describing intonation is of importance to several information retrieval tasks like the development of rāga and artist similarity measures. In our previous work, we proposed a compact representation of intonation based on the parametrization of the pitch histogram of a performance and demonstrated the usefulness of this representation through an explorative rāga recognition task in which we classified 42 vocal performances belonging to 3 rāgas using parameters of a single svara. In this paper, we extend this representation to employ context-based svara distributions, which are obtained with a different approach to find the pitches belonging to each svara. We quantitatively compare this method to our previous one, discuss the advantages, and the necessary melodic analysis to be carried out in future.

Signal analysis of Ney performances

Ney is an end-blown flute which is mainly used for Makam music. Although from the beginning of 20th century a score representation based on extending the Western musicis used, because of its rich articulation repertoire, actualNey music can not be totally represented by written score.Ney is still taught and transmitted orally in Turkey. Becauseof that the performance has a distinct and importantrole in Ney music. Therefore signal analysis of ney performancesis crucial for understanding the actual music.Another important aspect which is also a part of the performanceis the articulations that performers apply. In Makam music in Turkey none of the articulations are taught evennamed by teachers. Articulations in Ney are valuable for understanding the real performance. Since articulations are not taught and their places are not marked in the score, the choice and character of the articulation is unique for eachperformer which also makes each performance unique.Our method analyzes audio files of well known Turkish Ney players. In order to obtain our analysis data, we analyzed audio files of 8 different performers vary from 1920to 2000.

Mutation patterns of amino acid tandem repeats in the human proteome

Background: Amino acid tandem repeats are found in nearly one-fifth of human proteins. Abnormal expansion of these regions is associated with several human disorders. To gain further insight into the mutational mechanisms that operate in this type of sequence, we have analyzed a large number of mutation variants derived from human expressed sequence tags (ESTs).Results: We identified 137 polymorphic variants in 115 different amino acid tandem repeats. Of these, 77 contained amino acid substitutions and 60 contained gaps (expansions or contractions of the repeat unit). The analysis showed that at least about 21% of the repeats might be polymorphic in humans. We compared the mutations found in different types of amino acid repeats and in adjacent regions. Overall, repeats showed a five-fold increase in the number of gap mutations compared to adjacent regions, reflecting the action of slippage within the repetitive structures. Gap and substitution mutations were very differently distributed between different amino acid repeat types. Among repeats containing gap variants we identified several disease and candidate disease genes.Conclusion: This is the first report at a genome-wide scale of the types of mutations occurring in the amino acid repeat component of the human proteome. We show that the mutational dynamics of different amino acid repeat types are very diverse. We provide a list of loci with highly variable repeat structures, some of which may be potentially involved in disease.