Establishing a lineage for medical knowledge discovery

Medical science has a long history characterised by incidents of extraordinary insights that have resulted in a paradigm shift in the methodologies and approaches used and have moved the discipline forward. While knowledge discovery has much to offer medicine, it cannot be done in ignorance of either this history or the norms of modern medical investigation. This paper explores the lineage of medical knowledge acquisition and discusses the adverse perceptions that data mining techniques will have to surmount to gain acceptance.Sydney, NS

Molecular Biology at the bedside: the impact of Genomics on the practice of medicine

Imagine being a newborn baby, discharged home after delivery, with a most unusual gift, a compact disc (CD) carrying all data on "My Genome". The parents would be most anxious to play it on their home PC. Soon, they could discover whether their child has been spared those major single gene disorders which uncle John had before he died young. The doctors had told them they could be selected out when they had opted for pre-gestational diagnosis and selective fertilisation.peer-reviewe

Mesenchymal stem cells for management of rheumatoid arthritis : immune modulation, repair or both?

The authors are grateful for support to their research from Arthritis Research UK (grants 19271, 19429, 19667, 20050, 20775) and the Medical Research Council (grant no. MR/L020211/1)Peer reviewedPostprin

The Genetic Signature of Perineuronal Oligodendrocytes

Oligodendrocytes in the central nervous system can be categorized as precursors, myelin-forming, and non-myelinating perineuronal cells. The function of perineuronal oligodendrocytes is unknown; it was proposed that following injury, they may remyelinate denuded axons. We investigated these cells' potential. A combination of cell-specific tags, microarray technology and bioinformatics tools to identify gene expression differences between these subpopulations allowed us to capture the genetic signature of perineuronal oligodendrocytes. Here we report that perineuronal oligodendrocytes are configured for a dual role. As cells that embrace neuronal somata, they integrate a repertoire of transcripts designed to create their own code for communicating with neurons. But they maintain a reservoir of untranslated transcripts encoding the major myelin proteins for - we speculate - a demyelinating episode. We posit that the signature molecules, PDGFR-[alpha][beta] cytokine PDGF-CC, and transcription factor Pea3, used - among others - to define the non-myelinating phenotype, may be critical for mounting a myelinating programme during demyelination. Harnessing this capability is of therapeutic value for diseases such as multiple sclerosis. This is the first molecular characterization of an elusive neural cell

Cultural representations of mental illness in contemporary Japan

This paper presents the results of a research project aimed at studying the cultural representations of mental illness and related interventions models in contemporary Japan, and providing the basis for a comparison between Japanese and Italian mental health cultures. The research methodology is based on interviews with scholars and professionals from multiple disciplinary areas and fields of practice, in order to analyze the interactions between medical, social sciences’ and humanities’ discourse on mental illness. The results highlight the significance of home custody within the modernization of the country, between Edo and Meiji periods; the cultural frameworks of contemporary psychiatry’s action; what anti-psychiatry and the ‘critical’ reflection on mental illness represented within the academic debate; the new demands and potentialities connected to the spread of psychology within the mental health sector; remarkably new experiences of social integration with the contribution of arts

Proceedings: Regenerative Medicine for Lung Diseases: A CIRM Workshop Report.

The mission of the California Institute of Regenerative Medicine (CIRM) is to accelerate treatments to patients with unmet medical needs. In September 2016, CIRM sponsored a workshop held at the University of California, Los Angeles, to discuss regenerative medicine approaches for treatment of lung diseases and to identify the challenges remaining for advancing such treatments to the clinic and market approval. Workshop participants discussed current preclinical and clinical approaches to regenerative medicine in the lung, as well as the biology of lung stem cells and the role of stem cells in the etiology of various lung diseases. The outcome of this effort was the recognition that whereas transient cell delivery approaches are leading the way in the clinic, recent advances in the understanding of lung stem cell biology, in vitro and in vivo disease modeling, gene editing and replacement methods, and cell engraftment approaches raise the prospect of developing cures for some lung diseases in the foreseeable future. In addition, advances in in vitro modeling using lung organoids and "lung on a chip" technology are setting the stage for high quality small molecule drug screening to develop treatments for lung diseases with complex biology. Stem Cells Translational Medicine 2017;6:1823-1828

PAV ontology: provenance, authoring and versioning

Provenance is a critical ingredient for establishing trust of published scientific content. This is true whether we are considering a data set, a computational workflow, a peer-reviewed publication or a simple scientific claim with supportive evidence. Existing vocabularies such as DC Terms and the W3C PROV-O are domain-independent and general-purpose and they allow and encourage for extensions to cover more specific needs. We identify the specific need for identifying or distinguishing between the various roles assumed by agents manipulating digital artifacts, such as author, contributor and curator. We present the Provenance, Authoring and Versioning ontology (PAV): a lightweight ontology for capturing just enough descriptions essential for tracking the provenance, authoring and versioning of web resources. We argue that such descriptions are essential for digital scientific content. PAV distinguishes between contributors, authors and curators of content and creators of representations in addition to the provenance of originating resources that have been accessed, transformed and consumed. We explore five projects (and communities) that have adopted PAV illustrating their usage through concrete examples. Moreover, we present mappings that show how PAV extends the PROV-O ontology to support broader interoperability. The authors strived to keep PAV lightweight and compact by including only those terms that have demonstrated to be pragmatically useful in existing applications, and by recommending terms from existing ontologies when plausible. We analyze and compare PAV with related approaches, namely Provenance Vocabulary, DC Terms and BIBFRAME. We identify similarities and analyze their differences with PAV, outlining strengths and weaknesses of our proposed model. We specify SKOS mappings that align PAV with DC Terms.Comment: 22 pages (incl 5 tables and 19 figures). Submitted to Journal of Biomedical Semantics 2013-04-26 (#1858276535979415). Revised article submitted 2013-08-30. Second revised article submitted 2013-10-06. Accepted 2013-10-07. Author proofs sent 2013-10-09 and 2013-10-16. Published 2013-11-22. Final version 2013-12-06. http://www.jbiomedsem.com/content/4/1/3

Ancient Pbx-Hox signatures define hundreds of vertebrate developmental enhancers

Background: Gene regulation through cis-regulatory elements plays a crucial role in development and disease. A major aim of the post-genomic era is to be able to read the function of cis-regulatory elements through scrutiny of their DNA sequence. Whilst comparative genomics approaches have identified thousands of putative regulatory elements, our knowledge of their mechanism of action is poor and very little progress has been made in systematically de-coding them. Results: Here, we identify ancient functional signatures within vertebrate conserved non-coding elements (CNEs) through a combination of phylogenetic footprinting and functional assay, using genomic sequence from the sea lamprey as a reference. We uncover a striking enrichment within vertebrate CNEs for conserved binding-site motifs of the Pbx-Hox hetero-dimer. We further show that these predict reporter gene expression in a segment specific manner in the hindbrain and pharyngeal arches during zebrafish development. Conclusions: These findings evoke an evolutionary scenario in which many CNEs evolved early in the vertebrate lineage to co-ordinate Hox-dependent gene-regulatory interactions that pattern the vertebrate head. In a broader context, our evolutionary analyses reveal that CNEs are composed of tightly linked transcription-factor binding-sites (TFBSs), which can be systematically identified through phylogenetic footprinting approaches. By placing a large number of ancient vertebrate CNEs into a developmental context, our findings promise to have a significant impact on efforts toward de-coding gene-regulatory elements that underlie vertebrate development, and will facilitate building general models of regulatory element evolution