A new advance in alternative splicing databases: from catalogue to detailed analysis of regulation of expression and function of human alternative splicing variants

<p>Abstract</p> <p>Background</p> <p>Most human genes produce several transcripts with different exon contents by using alternative promoters, alternative polyadenylation sites and alternative splice sites. Much effort has been devoted to describing known gene transcripts through the development of numerous databases. Nevertheless, owing to the diversity of the transcriptome, there is a need for interactive databases that provide information about the potential function of each splicing variant, as well as its expression pattern.</p> <p>Description</p> <p>After setting up a database in which human and mouse splicing variants were compiled, we developed tools (1) to predict the production of protein isoforms from these transcripts, taking account of the presence of open reading frames and mechanisms that could potentially eliminate transcripts and/or inhibit their translation, i.e. nonsense-mediated mRNA decay and microRNAs; (2) to support studies of the regulation of transcript expression at multiple levels, including transcription and splicing, particularly in terms of tissue specificity; and (3) to assist in experimental analysis of the expression of splicing variants. Importantly, analyses of all features from transcript metabolism to functional protein domains were integrated in a highly interactive, user-friendly web interface that allows the functional and regulatory features of gene transcripts to be assessed rapidly and accurately.</p> <p>Conclusion</p> <p>In addition to identifying the transcripts produced by human and mouse genes, fast DB <url>http://www.fast-db.com</url> provides tools for analyzing the putative functions of these transcripts and the regulation of their expression. Therefore, fast DB has achieved an advance in alternative splicing databases by providing resources for the functional interpretation of splicing variants for the human and mouse genomes. Because gene expression studies are increasingly employed in clinical analyses, our web interface has been designed to be as user-friendly as possible and to be readily searchable and intelligible at a glance by the whole biomedical community.</p

Digital Healthcare Projects Policy Action Plan

Whilst the policies of the centre are designed to support a focused effort researching the field of information and communication technologies (ICTs), including increasingly pervasive communication networks, it is recognised that increasing processing power and the ability to transfer more information faster through both wired and wireless systems means that the developments will also include increased ability to search, filter and share both data and information. Our approach is to find new ways in which technologies can be used to meet the challenges facing health and healthcare in the next 10–15 years. ICTs can both enable and drive change in health and healthcare, and this raises social issues as well as technical ones. Particularly important is that ICTs may drive healthcare towards treating patients nearer (or in) their homes, putting greater emphasis upon bringing the patient more actively into the processes supporting their own healthcare contributing to the transition from the traditional ‘paternalistic’ model to one of negotiation and wider information sharing. . These technologies will generate vast amounts of health-related data. These data are made available to appropriate groups in a timely fashion. It must be processed to yield useful information. This raises questions about how any information generated is used. How is the data analysed? Who owns patient data? Most importantly, who should have access to patient data? The PSC policy documents aim to be both specific yet offer general advice. The intention is to provide cohesive guidance for projects and collective research effort yet provide specific direction to individuals that focus upon their needs. The field cross sections healthcare, pervasive systems and ECS groups. For this reason computer scientists offer to support this process through the provision of tools to steer users through establishing the most appropriate contacts and technology bases inside the pervasive systems centre so as to help find the ‘right’ technology partner and assist in building comprehensive records for collaborative efforts

Transantiago: On the Development of Public Transit in Large Cities

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

A Web/Grid Services Approach for Integration of Virtual Clinical &amp; Research Environments

Clinicans have responsibilities for audit and research, often participating in projects with basic scientist colleagues. Our work in a regional teaching hospital setting involves collaboration with the medical school computer services and builds upon work developed in computer science department as part of the Collaborative Orthopaedic Research Environment (CORE) project[1]. This has established a pilot study for proof of concept work. Users are mapped to a personal profile implemented using XML and a service oriented architecture (SOA)[2,3]. This bridges the e-Health and e-Science domains, addressing some of the basic questions of security and uptake

Multiyear trend in reproduction underpins interannual variation in gametogenic development of an Antarctic urchin.

Ecosystems and their biota operate on cyclic rhythms, often entrained by predictable, small-scale changes in their natural environment. Recording and understanding these rhythms can detangle the effect of human induced shifts in the climate state from natural fluctuations. In this study, we assess long-term patterns of reproductive investment in the Antarctic sea urchin, Sterechinus neumayeri, in relation to changes in the environment to identify drivers of reproductive processes. Polar marine biota are sensitive to small changes in their environment and so serve as a barometer whose responses likely mirror effects that will be seen on a wider global scale in future climate change scenarios. Our results indicate that seasonal reproductive periodicity in the urchin is underpinned by a multiyear trend in reproductive investment beyond and in addition to, the previously reported 18–24 month gametogenic cycle. Our model provides evidence that annual reproductive investment could be regulated by an endogenous rhythm since environmental factors only accounted for a small proportion of the residual variation in gonad index. This research highlights a need for multiyear datasets and the combination of biological time series data with large-scale climate metrics that encapsulate multi-factorial climate state shifts, rather than using single explanatory variables to inform changes in biological processes

A narration of a physical science teacher's experience of implementing a new curriculum

This article narrates the lived experiences of a Physical Science teacher named Thobani (pseudonym) in implementing a new curriculum in South Africa. Drawing on the work of Husserl and Heidegger, the article describes the objects of direct experience in Thobani's consciousness about his life as a learner and teacher as revealed during an in-depth semi-structured interview conducted from two perspectives. The genealogical part of the interview chronicled how his knowledge of Physical Science had unfolded in his life as a learner and subsequently as a teacher; the portraiture perspective recounted the often traumatic events of his personal life and the circumstances that had informed his decision to become a teacher. Theoretically, the findings reveal how an incompetent Physical Science teacher had hampered his understanding of the fundamentals of the subject, and how the lack of support from the Department of Education and his head of department had retarded the implementation process. The insights gleaned from this phenomenological investigation into the thought processes of a teacher introduced to a new curriculum could have potentially transformative effects for policy-makers, curriculum planners and teacher educators at a time when South African teachers are yet again faced with the implementation of a new curriculum.DHE

Estimating turbulent velocities in the elliptical galaxies NGC 5044 and NGC 5813

The interstellar and intra-cluster medium in giant elliptical galaxies and clusters of galaxies is often assumed to be in hydrostatic equilibrium. Numerical simulations, however, show that about 5-30% of the pressure in a cluster is provided by turbulence induced by, for example, the central AGN and merger activity. We aim to put constraints on the turbulent velocities and turbulent pressure in the ICM of the giant elliptical galaxies NGC 5044 and NGC 5813 using XMM-Newton RGS observations. The magnitude of the turbulence is estimated using the Fe XVII lines at 15.01 A, 17.05 A, and 17.10 A in the RGS spectra. At low turbulent velocities, the gas becomes optically thick in the 15.01 A line due to resonant scattering, while the 17 A lines remain optically thin. By comparing the (I(17.05)+I(17.10))/I(15.01) line ratio from RGS with simulated line ratios for different Mach numbers, the level of turbulence is constrained. The measurement is limited by systematic uncertainties in the atomic data, which are at the 20-30% level. We find that the line ratio in NGC 5813 is significantly higher than in NGC 5044. This difference can be explained by a higher level of turbulence in NGC 5044. The high turbulent velocities and the fraction of the turbulent pressure support of >40% in NGC 5044, assuming isotropic turbulence, confirm that it is a highly disturbed system, probably due to an off-axis merger. The turbulent pressure support in NGC 5813 is more modest at 15-45%. The (I(17.05)+I(17.10))/I(15.01) line ratio in an optically thin plasma, calculated using AtomDB v2.0.1, is 2 sigma above the ratio measured in NGC 5044, which cannot be explained by resonant scattering. This shows that the discrepancies between theoretical, laboratory, and astrophysical data on Fe XVII lines need to be reduced to improve the accuracy of the determination of turbulent velocities using resonant scattering.Comment: 11 pages, 5 figures, accepted for publication in A&

An orchestrated intron retention program in meiosis controls timely usage of transcripts during germ cell differentiation

Global transcriptome reprogramming during sper-matogenesis ensures timely expression of factors in each phase of male germ cell differentiation. Sper-matocytes and spermatids require particularly exten-sive reprogramming of gene expression to switch from mitosis to meiosis and to support gamete morphogenesis. Here, we uncovered an extensive alternative splicing program during this transmeiotic differentiation. Notably, intron retention was largely the most enriched pattern, with spermatocytes showing generally higher levels of retention compared with spermatids. Retained introns are characterized by weak splice sites and are enriched in genes with strong relevance for gamete func-tion. Meiotic intron-retaining transcripts (IRTs) were exclusively localized in the nucleus. However, differ-ently from other developmentally regulated IRTs, they are stable RNAs, showing longer half-life than properly spliced transcripts. Strikingly, fate-mapping experiments revealed that IRTs are recruited onto polyribosomes days after synthesis. These studies reveal an unexpected function for regulated intron retention in modulation of the timely expression of select transcripts during spermatogenesis