Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

Big data and other challenges in the quest for orthologs.

Given the rapid increase of species with a sequenced genome, the need to identify orthologous genes between them has emerged as a central bioinformatics task. Many different methods exist for orthology detection, which makes it difficult to decide which one to choose for a particular application. Here, we review the latest developments and issues in the orthology field, and summarize the most recent results reported at the third 'Quest for Orthologs' meeting. We focus on community efforts such as the adoption of reference proteomes, standard file formats and benchmarking. Progress in these areas is good, and they are already beneficial to both orthology consumers and providers. However, a major current issue is that the massive increase in complete proteomes poses computational challenges to many of the ortholog database providers, as most orthology inference algorithms scale at least quadratically with the number of proteomes. The Quest for Orthologs consortium is an open community with a number of working groups that join efforts to enhance various aspects of orthology analysis, such as defining standard formats and datasets, documenting community resources and benchmarking. AVAILABILITY AND IMPLEMENTATION: All such materials are available at http://questfororthologs.org. CONTACT: erik.sonnhammer@scilifelab.se or c.dessimoz@ucl.ac.uk.

ROQUIN/RC3H1 alterations are not found in angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell Lymphoma (AITL) is one of the most frequent T-cell lymphoma entities. Follicular helper T lymphocytes (TFH) are recognized as the normal cellular counterpart of the neoplastic component. Despite a clonal T-cell feature and few described recurrent cytogenetic abnormalities, a driving oncogenic event has not been identified so far. It has been recently reported that in mice, heterozygous inactivation of Roquin/Rc3h1, a RING type E3 ubiquitine ligase, recapitulates many of the clinical, histological, and cellular features associated with human AITL. In this study we explored whether ROQUIN alterations could be an initial event in the human AITL oncogenic process. Using microarray and RT-PCR analyses, we investigated the levels of ROQUIN transcripts in TFH tumor cells purified from AITL (n = 8) and reactive tonsils (n = 12) and found similar levels of ROQUIN expression in both. Moreover, we also demonstrated that ROQUIN protein was expressed by AITL TFH (PD1+) cells. We then analysed ROQUIN coding sequence in 12 tumor cell-rich AITL samples and found no mutation in any of the samples. Finally, we analysed the expression of MiR101, a putative partner of ROQUIN involved in the modulation of ICOS expression and found similar levels of expression in tumor and reactive TFH. Altogether, this study shows that neither alteration of ROQUIN gene nor deregulation of miR101 expression is likely to be a frequent recurrent event in AITL.

Modelling the effect of minor orthopaedic day surgery on patient mood at the early post-operative period: a prospective population-based cohort study.

OBJECTIVE: The effect of minor orthopaedic day surgery (MiODS) on patient's mood. METHODS: A prospective population-based cohort study of 148 consecutive patients with age above 18 and less than 65, an American Society of Anaesthesiology (ASA) score of 1, and the requirement of general anaesthesia (GA) were included. The Medical Outcomes Study - Short Form 36 (SF-36), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were used pre- and post-operatively. RESULTS: The mean physical component score of SF-36 before surgery was 45.3 (SD=+/-10.1) and 8 weeks following surgery was 44.9 (SD=+/-11.04) [n=148, p=0.51, 95% CI=(-1.03 to 1.52)]. For the measurement of the changes in mood using BDI, BAI and SF-36, latent construct modelling was employed to increase validity. The covariance between mood pre- and post-operatively (cov=69.44) corresponded to a correlation coefficient, r=0.88 indicating that patients suffering a greater number of mood symptoms before surgery continue to have a greater number of symptoms following surgery. When the latent mood constructs were permitted to have different means the model fitted well with chi(2) (df=1)=0.86 for which p=0.77, thus the null hypothesis that MiODS has no effect on patient mood was rejected. CONCLUSIONS: MiODS affects patient mood which deteriorates at 8 weeks post-operatively regardless of the pre-operative patient mood state. More importantly patients suffering a greater number of mood symptoms before MiODS continue to have a greater number of symptoms following surgery.

The InterPro protein families database: the classification resource after 15 years.

The InterPro database (http://www.ebi.ac.uk/interpro/) is a freely available resource that can be used to classify sequences into protein families and to predict the presence of important domains and sites. Central to the InterPro database are predictive models, known as signatures, from a range of different protein family databases that have different biological focuses and use different methodological approaches to classify protein families and domains. InterPro integrates these signatures, capitalizing on the respective strengths of the individual databases, to produce a powerful protein classification resource. Here, we report on the status of InterPro as it enters its 15th year of operation, and give an overview of new developments with the database and its associated Web interfaces and software. In particular, the new domain architecture search tool is described and the process of mapping of Gene Ontology terms to InterPro is outlined. We also discuss the challenges faced by the resource given the explosive growth in sequence data in recent years. InterPro (version 48.0) contains 36 766 member database signatures integrated into 26 238 InterPro entries, an increase of over 3993 entries (5081 signatures), since 2012.

Risk factors of postictal generalized EEG suppression in generalized convulsive seizures.

OBJECTIVE: To identify the clinical determinants of occurrence of postictal generalized EEG suppression (PGES) after generalized convulsive seizures (GCS). METHODS: We reviewed the video-EEG recordings of 417 patients included in the REPO2MSE study, a multicenter prospective cohort study of patients with drug-resistant focal epilepsy. According to ictal semiology, we classified GCS into 3 types: tonic-clonic GCS with bilateral and symmetric tonic arm extension (type 1), clonic GCS without tonic arm extension or flexion (type 2), and GCS with unilateral or asymmetric tonic arm extension or flexion (type 3). Association between PGES and person-specific or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. RESULTS: A total of 99 GCS in 69 patients were included. Occurrence of PGES was independently associated with GCS type (p < 0.001) and lack of early administration of oxygen (p < 0.001). Odds ratio (OR) for GCS type 1 in comparison with GCS type 2 was 66.0 (95% confidence interval [CI 5.4-801.6]). In GCS type 1, risk of PGES was significantly increased when the seizure occurred during sleep (OR 5.0, 95% CI 1.2-20.9) and when oxygen was not administered early (OR 13.4, 95% CI 3.2-55.9). CONCLUSION: The risk of PGES dramatically varied as a function of GCS semiologic characteristics. Whatever the type of GCS, occurrence of PGES was prevented by early administration of oxygen.

L'utilisation de l'Evangile de Thomas dans la recherche actuelle sur les paroles de Jésus

(Résumé de l'ouvrage) Ce volume regroupe des travaux menés sur le Jésus de l'histoire par des spécialistes de cette question fondatrice. Celle-ci connait, en effet, de vigoureuses impulsions dues à l'application de nouvelles méthodologies aux effets inattendus: sociologie du judaisme ancien, anthropologie des sociétés agraires, utilisation des écrits apocryphes chrétiens. Pour la première fois, des savants mondialement réputés sont présentés en français tels John S. Kloppenborg (Toronto) ou Ed P. Sanders (Durham). L'ouvrage est construit en sept parties: l'état de la recherche, le judaisme au temps de Jésus, le coeur de la théologie de Jésus, la tradition extracanonique chrétienne et la question du Jésus historique, Jésus dans le Nouveau Testament, les lectures juives de Jésus, le Jésus historique et la théologie.

Early versus delayed application of Thomas splints in patients with isolated femur shaft fractures: The benefits quantified.

AIMS: To investigate and quantify the clinical benefits of early versus delayed application of Thomas splints in patients with isolated femur shaft fractures. MATERIALS AND METHODS: Level IV retrospective clinical and radiological analysis of patients presenting from January to December 2012 at a Level 1 Trauma Unit. All skeletally mature patients with isolated femur shaft fractures independently of their mechanism of injury were included. Exclusion criteria were: ipsilateral fracture of the lower limb, neck and supracondylar femur fractures, periprosthetic and incomplete fractures. Their clinical records were analysed for blood transfusion requirements, pulmonary complications, surgery time, duration of hospital stay and analgesic requirements. RESULTS: A total of 106 patients met our inclusion criteria. There were 74 males and 32 females. Fifty seven (54%) patients were in the 'early splinted' group and 49 patients (46%) were in the 'delayed splinted' group (P&gt;0.05). The need for blood transfusion was significantly reduced in the 'early splinted' group (P=0.04). There was a significantly higher rate of pulmonary complications in the 'delayed splinted' group (P=0.008). All other parameters were similar between the two groups. CONCLUSION: The early application of Thomas splints for isolated femur fractures in non-polytraumatised patients has a clinically and statistically significant benefit of reducing the need for blood transfusions and the incidence of pulmonary complications.