Global investigation of protein–protein interactions in yeast Saccharomyces cerevisiae using re-occurring short polypeptide sequences

Protein–protein interaction (PPI) maps provide insight into cellular biology and have received considerable attention in the post-genomic era. While large-scale experimental approaches have generated large collections of experimentally determined PPIs, technical limitations preclude certain PPIs from detection. Recently, we demonstrated that yeast PPIs can be computationally predicted using re-occurring short polypeptide sequences between known interacting protein pairs. However, the computational requirements and low specificity made this method unsuitable for large-scale investigations. Here, we report an improved approach, which exhibits a specificity of ∼99.95% and executes 16 000 times faster. Importantly, we report the first all-to-all sequence-based computational screen of PPIs in yeast, Saccharomyces cerevisiae in which we identify 29 589 high confidence interactions of ∼2 × 107 possible pairs. Of these, 14 438 PPIs have not been previously reported and may represent novel interactions. In particular, these results reveal a richer set of membrane protein interactions, not readily amenable to experimental investigations. From the novel PPIs, a novel putative protein complex comprised largely of membrane proteins was revealed. In addition, two novel gene functions were predicted and experimentally confirmed to affect the efficiency of non-homologous end-joining, providing further support for the usefulness of the identified PPIs in biological investigations

RoboDOMO, un robot d’assistance aux personnes âgées et dépendantes dans un environnement d’objets communicants

International audienceIn this article, we present a portfolio of mobiquitous information services for assisted living built around a robot (RoboDOMO project). RoboDOMO is a mobile PC, which has a camera and which could be remotely manipulated by a cell phone. We integrated wireless objects to communicate with the robot and potentially help or send alerts: fall captors, NFC drugs, etc. These mobiquitous services concern pleasure, day life agenda, memory exercises and security. We proposed an open standardized architecture to integrate any type of captor and sensor. Multidisciplinary researchs are being conducted in Computer Science, Law, Economics (business models) and Sociology (Robot shape and service acceptability) around RoboDOMO.Cet article décrit principalement un bouquet de services mobiquitaires basé sur un robot mobile et un environnement d’objets communicants, qui permet de faciliter la vie de personnes en situation de dépendance. RoboDOMO est un prototype de robot d’assistance ; il est capable d’intégrer et fournir des informations en provenance de multiples sources sans fil, de faciliter la communication avec une tierce personne grâce à la visioconférence, ou encore d’être piloté à distance par le téléphone mobile de la famille ou du corps médical. La mise en œuvre de RoboDOMO et de son environnement d’objets communicants (capteurs, tags NFC, etc.) au sein d’une architecture standardisée ouverte est présentée dans son contexte pluridisciplinaire

RoboDOMO, un robot d’assistance aux personnes âgées et dépendantes dans un environnement d’objets communicants

Cet article décrit principalement un bouquet de services mobiquitaires basé sur un robot mobile et un environnement d’objets communicants, qui permet de faciliter la vie de personnes en situation de dépendance. RoboDOMO est un prototype de robot d’assistance ; il est capable d’intégrer et fournir des informations en provenance de multiples sources sans fil, de faciliter la communication avec une tierce personne grâce à la visioconférence, ou encore d’être piloté à distance par le téléphone mobile de la famille ou du corps médical. La mise en œuvre de RoboDOMO et de son environnement d’objets communicants (capteurs, tags NFC, etc.) au sein d’une architecture standardisée ouverte est présentée dans son contexte pluridisciplinaire.In this article, we present a portfolio of mobiquitous information services for assisted living built around a robot (RoboDOMO project). RoboDOMO is a mobile PC, which has a camera and which could be remotely manipulated by a cell phone. We integrated wireless objects to communicate with the robot and potentially help or send alerts: fall captors, NFC drugs, etc. These mobiquitous services concern pleasure, day life agenda, memory exercises and security. We proposed an open standardized architecture to integrate any type of captor and sensor. Multidisciplinary researchs are being conducted in Computer Science, Law, Economics (business models) and Sociology (Robot shape and service acceptability) around RoboDOMO

Identification and cloning of a new western Epstein-Barr virus strain that replicates efficiently in primary B cells.

The Epstein-Barr virus (EBV) causes human cancers, and epidemiological studies have shown that lytic replication is a risk factor for some of these tumors. This fits with the observation that EBV M81, which was isolated from a Chinese patient with nasopharyngeal carcinoma, induces potent virus production and increases the risk of genetic instability in infected B cells. To find out whether this property extends to viruses found in other parts of the world, we investigated 22 viruses isolated from Western patients. While one-third of the viruses hardly replicated, the remaining viruses showed variable levels of replication, with three isolates replicating at levels close to that of M81 in B cells. We cloned one strongly replicating virus into a bacterial artificial chromosome (BAC); the resulting recombinant virus (MSHJ) retained the properties of its nonrecombinant counterpart and showed similarities to M81, undergoing lytic replication in vitro and in vivo after 3 weeks of latency. In contrast, B cells infected with the nonreplicating Western B95-8 virus showed early but abortive replication accompanied by cytoplasmic BZLF1 expression. Sequencing confirmed that rMSHJ is a Western virus, being genetically much closer to 695-8 than to M81. Spontaneous replication in rM81- and rMSHJ-infected B cells was dependent on phosphorylated Btk and was inhibited by exposure to ibrutinib, opening the way to clinical intervention in patients with abnormal EBV replication. As rMSHJ contains the complete EBV genome and induces lytic replication in infected B cells, it is ideal to perform genetic analyses of all viral functions in Western strains and their associated diseases.IMPORTANCE The Epstein-Barr virus (EBV) infects the majority of the world population but causes different diseases in different countries. Evidence that lytic replication, the process that leads to new virus progeny, is linked to cancer development is accumulating. Indeed, viruses such as M81 that were isolated from Far Eastern nasopharyngeal carcinomas replicate strongly in B cells. We show here that some viruses isolated from Western patients, including the MSHJ strain, share this property. Moreover, replication of both M81 and of MSHJ was sensitive to ibrutinib, a commonly used drug, thereby opening an opportunity for therapeutic intervention. Sequencing of MSHJ showed that this virus is quite distant from M81 and is much closer to nonreplicating Western viruses. We conclude that Western EBV strains are heterogeneous, with some viruses being able to replicate more strongly and therefore being potentially more pathogenic than others, and that the virus sequence information alone cannot predict this property

Functional analysis of the Saccharomyces cerevisiae DUP240 multigene family reveals membrane-associated proteins that are not essential for cell viability.

The DUP240 gene family of Saccharomyces cerevisiae is composed of 10 members. They encode proteins of about 240 amino acids which contain two predicted transmembrane domains. Database searches identified only one homologue in the closely related species Saccharomyces bayanus, indicating that the DUP240 genes encode proteins specific to Saccharomyces sensu stricto. The short-flanking homology PCR gene-replacement strategy with a variety of selective markers for replacements, and classical genetic methods, were used to generate strains deleted for all 10 DUP240 genes. All of the knock-out strains were viable and had similar growth kinetics to the wild-type. Two-hybrid screens, hSos1p fusions and GFP fusions were carried out; the results indicated that the Dup240 proteins are membrane associated, and that some of them are concentrated around the plasma membrane.journal articleresearch support, non-u.s. gov't2002 Julimporte

Core curriculum for the heart rhythm specialist: executive summary

Heart rhythm (HR) management is rapidly developing as a subspecialty within cardiology, and it is imperative to promote and ensure sufficient and homogeneous training and qualification amongst professionals in Europe. This has led the European Society of Cardiology, through the European Heart Rhythm Association (EHRA), to organize a European Core Curriculum for the HR specialist through the following: definition of the scope of the HR speciality (Syllabus), development of minimum standards and objectives for training in HR management (Curriculum), development of a model to certify HR professionals and teaching units (Accreditation), and development of a Registry for European HR accredited professionals and teaching units and its activity (Registries). The duration of the training period should be of a minimum of 2 years following general cardiology training. During this period, the trainee must develop the required knowledge, practical skills, behaviours, and attitudes to manage HR patients. The trainee must be involved in a minimum number of different procedures and achieve specified levels of competence. The training centre should be integrated within a full-service cardiology department. Assessment of the trainee and the training programmes should include reports by the training programme supervisor and the national society HR organizations, a logbook of procedures, written examinations, and assessment of professionalism. The EHRA presently requires the trainee to pass the EHRA accreditation exams (invasive EP and cardiac pacing and ICDs). Continuous learning and practice are required to maintain standards and practice and because substantial changes may occur in clinical practice or the health-care environment

Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789

We sequenced the genome of Saccharomyces cerevisiae strain YJM789, which was derived from a yeast isolated from the lung of an AIDS patient with pneumonia. The strain is used for studies of fungal infections and quantitative genetics because of its extensive phenotypic differences to the laboratory reference strain, including growth at high temperature and deadly virulence in mouse models. Here we show that the ≈12-Mb genome of YJM789 contains ≈60,000 SNPs and ≈6,000 indels with respect to the reference S288c genome, leading to protein polymorphisms with a few known cases of phenotypic changes. Several ORFs are found to be unique to YJM789, some of which might have been acquired through horizontal transfer. Localized regions of high polymorphism density are scattered over the genome, in some cases spanning multiple ORFs and in others concentrated within single genes. The sequence of YJM789 contains clues to pathogenicity and spurs the development of more powerful approaches to dissecting the genetic basis of complex hereditary traits