Biomedical Scientific Community Research Articles

Differential Tandem Mass Spectrometry-Based Cross-Linker: A New Approach for High Confidence in Identifying Protein Cross-Linking

Chemical cross-linking and mass spectrometry are now widely used to analyze large-scale protein-protein interactions. The major challenge in cross-linking approaches is the complexity of the mass spectrometric data. New approaches are required that can identify cross-linked peptides with high-confidence and establish a user-friendly analysis protocol for the biomedical scientific community. Here, we introduce a novel cross-linker that can be selectively cleaved in the gas phase using two differential tandem mass-spectrometric fragmentation methods, such as collision-induced or electron transfer dissociation (CID and ETD). This technique produces two signature mass spectra of the same cross-linked peptide, thereby producing high confidence in identifying the sites of interaction. Further tandem mass spectrometry can also give additional confidence on the peptide sequences. We demonstrate a proof-of-concept for this method using standard peptides and proteins. Peptides and proteins were cross-linked and their fragmentation characteristics were analyzed using CID and ETD tandem mass spectrometry. Two sequential cleavages unambiguously identified cross-linked peptides. In addition, the labeling efficiency of the new cross-linker was evaluated in macrophage immune cells after stimulation with the microbial ligand lipopolysaccharide and subsequent pulldown experiments with biotin-avidin affinity chromatography. We believe this strategy will help advance insights into the structural biology and systems biology of cell signaling.

A High-Resolution SNP Array-Based Linkage Map Anchors a New Domestic Cat Draft Genome Assembly and Provides Detailed Patterns of Recombination.

High-resolution genetic and physical maps are invaluable tools for building accurate genome assemblies, and interpreting results of genome-wide association studies (GWAS). Previous genetic and physical maps anchored good quality draft assemblies of the domestic cat genome, enabling the discovery of numerous genes underlying hereditary disease and phenotypes of interest to the biomedical science and breeding communities. However, these maps lacked sufficient marker density to order thousands of shorter scaffolds in earlier assemblies, which instead relied heavily on comparative mapping with related species. A high-resolution map would aid in validating and ordering chromosome scaffolds from existing and new genome assemblies. Here, we describe a high-resolution genetic linkage map of the domestic cat genome based on genotyping 453 domestic cats from several multi-generational pedigrees on the Illumina 63K SNP array. The final maps include 58,055 SNP markers placed relative to 6637 markers with unique positions, distributed across all autosomes and the X chromosome. Our final sex-averaged maps span a total autosomal length of 4464 cM, the longest described linkage map for any mammal, confirming length estimates from a previous microsatellite-based map. The linkage map was used to order and orient the scaffolds from a substantially more contiguous domestic cat genome assembly (Felis catus v8.0), which incorporated ∼20 × coverage of Illumina fragment reads. The new genome assembly shows substantial improvements in contiguity, with a nearly fourfold increase in N50 scaffold size to 18 Mb. We use this map to report probable structural errors in previous maps and assemblies, and to describe features of the recombination landscape, including a massive (∼50 Mb) recombination desert (of virtually zero recombination) on the X chromosome that parallels a similar desert on the porcine X chromosome in both size and physical location.

Twitter K-H networks in action: Advancing biomedical literature for drug search

The importance of searching biomedical literature for drug interaction and side-effects is apparent. Current digital libraries (e.g., PubMed) suffer infrequent tagging and metadata annotation updates. Such limitations cause absence of linking literature to new scientific evidence. This demonstrates a great deal of challenges that stand in the way of scientists when searching biomedical repositories. In this paper, we present a network mining approach that provides a bridge for linking and searching drug-related literature. Our contributions here are two fold: (1) an efficient algorithm called HashPairMiner to address the run-time complexity issues demonstrated in its predecessor algorithm: HashnetMiner, and (2) a database of discoveries hosted on the web to facilitate literature search using the results produced by HashPairMiner. Though the K-H network model and the HashPairMiner algorithm are fairly young, their outcome is evidence of the considerable promise they offer to the biomedical science community in general and the drug research community in particular.

PDBe: Protein Data Bank in Europe

The Protein Data Bank in Europe (pdbe.org) is a founding member of the Worldwide PDB consortium (wwPDB; wwpdb.org) and as such is actively engaged in the deposition, annotation, remediation and dissemination of macromolecular structure data through the single global archive for such data, the PDB. Similarly, PDBe is a member of the EMDataBank organisation (emdatabank.org), which manages the EMDB archive for electron microscopy data. PDBe also develops tools that help the biomedical science community to make effective use of the data in the PDB and EMDB for their research. Here we describe new or improved services, including updated SIFTS mappings to other bioinformatics resources, a new browser for the PDB archive based on Gene Ontology (GO) annotation, updates to the analysis of Nuclear Magnetic Resonance-derived structures, redesigned search and browse interfaces, and new or updated visualisation and validation tools for EMDB entries.

AFRICA BUILD: Creating Web 2.0 Communities of Biomedical Researchers

Background and Purpose: Health researchers need access to continuing education and specialized advice to improve the quality, efficiency and accessibility of health systems. The creation of communities of researchers can provide the information necessary for their daily work in addition to strengthening the links between researchers. In this context, Web 2.0 technologies can facilitate the establishment of these communities. The AFRICA BUILD project aims to promote health research through the creation of virtual communities of health researchers, educators and practitioners, and the use of Information and Communication Technologies. This paper highlights the main findings and challenges found in the development of these communities. Methods: We have developed a social platform, the AFRICA BUILD Portal (ABP), which integrates health research related didactic contents and resources, as well as tools that facilitate collaboration. This portal has been developed following three principles: (i) use of free and open source tools, (ii) adaptation of these tools to low bandwidth connections, and (iii) creation of a Euro-African community of developers for the sustainability of the ABP. Results: Several communities of users were initiated within the ABP, mainly structured in three types according to: the organization or country to which they belong, the specific area they are working in, and researchers from two pilots courses on HIV/AIDS and Reproductive Health Research. Conclusions: Project partners and associates, who form several communities of users, currently use the ABP. The main challenges faced in the creation of these communities are: the language, a need for facilitators for the discussions and interactions, and the motivation of some members to actively participate and contribute in exchanges. In future steps, we plan to develop new functionalities within the ABP and disseminate the platform to the biomedical scientific community in Africa, fostering the creation of African communities of biomedical researchers. Keywords: Community Networks, Health Research, Social Media

Informatics that works for you

Just 10 years ago ‘informatics’ was a relatively unknown concept to the healthcare and biomedical science communities. Over the past years, the field expanded significantly and informatics became not only well known, but also an integral part of daily business in these communities. Accordingly, JAMIA has been continuously expanding the informatics pyramid of published work, from the foundational work upon which important applications are built (such as new algorithms and innovative approaches), all the way to illustrative experiences of system implementations that have generalizable lessons and randomized trials of informatics interventions. Practitioners suggest that JAMIA should publish a larger number of applied articles that describe the design, implementation, or evaluation of systems. Academics suggest that JAMIA should publish a larger quantity of foundational research reports. Defining the boundary can be challenging; what some consider applied work may be considered somewhat theoretical by others. Whether there is a dividing line between theory and practice of informatics and where this line would sit does not really matter (hence our section …

Informatics Infrastructure for the Australian Neuroscience Community: The Multi-modal Australian ScienceS Imaging and Visualisation Environment and the Characterisation Virtual Laboratory

Informatics Infrastructure for the Australian Neuroscience Community: The Multi-modal Australian ScienceS Imaging and Visualisation Environment and the Characterisation Virtual Laboratory

MASSIVE: Applications in Neuroscience

MASSIVE: Applications in Neuroscience

Exercise: Great for Heart Health, Just as Great for Cardiac Preconditioning Research

Ischemic heart disease remains a leading cause of morbidity and mortality in the United States and other industrialized countries [1]. Ongoing research efforts within the biomedical science community seek to discover counter therapies that will mitigate ischemic damage in those with coronary artery disease. Candidate therapies are intended to invoke cardioprotection by pharmacologic activation of endogenous mechanisms of cellular protection [2]. In concept the process of pharmacologic development is fundamentally simple: a cardioprotective pathway against ischemic injury is discovered, animal-based experiments provide proof of concept for pharmacologic induction of cardioprotection, and then clinical trials are undertaken. The reality, however, is somewhat more complicated. Within the context of discovery at different organizational levels (isolated cells, isolated organs, whole animal), numerous cellular pathways that elicit robust cardioprotection against ischemic injury are now well characterized [3]. Translation of this knowledge into clinical practice has proven far more difficult than expected. The point is famously articulated in a 2004 position paper by preeminent physicians and scientists is Circulation Research, “over the past 30 years, hundreds of experimental interventions (both pharmacologic and nonpharmacologic) have been reported to protect the ischemic myocardium in experimental animals; however, with the exception of early reperfusion, none has been translated into clinical practice” [4]. Given the collective effort to date, this is the central question: What scientific breakthrough is needed to translate our understanding of cardiac preconditioning into clinical practice? The underlying premise of this editorial is that the major limitation of cardiac preconditioning research is the nature of the stimulus, which traditionally has been derived from ischemia-induced adaptations.

The International Mouse Phenotyping Consortium: past and future perspectives on mouse phenotyping

Determining the function of all mammalian genes remains a major challenge for the biomedical science community in the 21st century. The goal of the International Mouse Phenotyping Consortium (IMPC) over the next 10years is to undertake broad-based phenotyping of 20,000 mouse genes, providing an unprecedented insight into mammalian gene function. This short article explores the drivers for large-scale mouse phenotyping and provides an overview of the aims and processes involved in IMPC mouse production and phenotyping.

How the UK Can Lead the Terrestrial Translation of Biomedical Advances Arising from Lunar Exploration Activities

Terrestrial translation of biomedical advances is insufficient justification for lunar exploration. However, terrestrial translation should be viewed as a critical part of the cycle of mission planning, execution and review, both in terms of the progress of space exploration, but also of sustained life on Earth. Thus, both the mission and its potential to benefit mankind are increased by the adoption of human-based exploration of the lunar surface. Whilst European biomedical sciences have grown in stature, there remains a gap between space biomedical science and terrestrial medical application. As such, an opportunity for the UK to take a sustainable leadership role exists by utilising its biomedical science community, socialised health care system (National Health Service) and defined mechanisms to determine the clinical efficacy and cost-effectiveness upon health and wellbeing (i.e. National Institute Clinical Excellence), aiding the difficult process of health care rationing. By focusing upon exploitation of the more scientifically rewarding, potentially long-term and more terrestrially analogous challenge of lunar habitation, the UK would circumnavigate the current impediments to International Space Station utilisation. Early engagement in lunar exploration would promote the UK, and its adoption of a leadership role incorporating a considered approach to the development of space biomedicine with an eye to its terrestrial value. For instance, prolonged lunar habitation could provide an ‘ideal controlled environment’ for investigation of medical interventions, in particular multiple interactions (e.g. between exercise and nutrition), a model of accelerated aging and a number of chronic pathologies, including those related to disuse. Lunar advances could provide a springboard for individualized medicine, insights into occupational and de-centralised medicine (e.g. telemedicine) and act as a stimulus for biomedical innovation and understanding. Leadership in biomedical science activities would retain mission critically (and thus avoid obsolesce) so long as a human is involved (irrespective of specific mission architecture) and could be used to leverage opportunities for UK-based institutions, companies and individuals, most notably current ESA astronaut candidate Major Tim Peake. A combination of ESA engagement and national support for space biomedical sciences via research councils (e.g. Medical Research Council) could facilitate a virtuous circle of investment, advancement and socio-economic return invigorating the NHS, education, and key research initiatives such as ESA Harwell, UK Centre for Medical Research and Innovation, and the newly instigated Academic Health Science Centres. Such a strategy could also boost private space enterprise within the UK including the creation of a space port and could help retain the UK’s position as a European aerospace transportation, services and legislative hub. By focusing upon its biomedical strength within a multi-faceted but co-ordinated strategy of engagement, the UK could reap significant socio-economic benefits for the UK and its citizens, be they on the Moon, or the Earth.

The increasing impact of Oral Diseases

Despite the many shortcomings of reducing the value and status of a journal to an impact factor (IF) rating, these numbers do indicate something useful to the biomedical science community about journal esteem. As a consequence, IFs influence what journals people decide to read and in which journals people decide to publish. We are writing now, because recently Journal Citation Reports (Thompson Reuters) released the 2008 Impact Factors for biomedical science journals. Oral Diseases saw a solid increase in its IF and a marked increase in its ranking relative to other journals in the category ‘Dentistry, Oral Surgery and Medicine’. As shown in Figure 1, this is the second consecutive year that Oral Diseases has seen a notable increase in its IF. After several year of having its IF hovering about 1.5, in 2007 Oral Diseases’ IF was 1.945 and this year it is 2.087. Perhaps more importantly, Oral Diseases’ relative ranking in its journal category has increased from 21/49 in 2006 to 17/51 in 2007 to 9/55 in 2008. Oral Diseases’ impact factor 2005–2008 Although the progress seems to be real over the past 3 years, Oral Diseases still has not reached the level to which we aspired when we began to co-edit the Journal in 2005. Our two goals were for Oral Diseases to have an IF ∼3.5 and to make Oral Diseases the journal to read in the head and neck sciences. We have much more to do before Oral Diseases reaches both goals, but we are making progress. While we would like to believe that our editorial philosophy and our work ethic have in some way contributed to this progress, the change most obviously comes from the quality and nature of the manuscripts being submitted. In that regard, it is interesting to look at the top articles cited and downloaded recently. For example, for the former we have good data for the year 2006, i.e. if you look at the top five articles by number of citations made during 2007 for manuscripts that were published in Oral Diseases during 2006, you find an interesting mix of topics (Table 1). Included are papers on mucosal diseases, developmental biology, stem cells, and oral sequelae of systemic conditions, i.e. reflective of a real link between oral tissues to the rest of the body. Similarly, a comparable pattern emerges if one considers the number and subject matter of the most frequently downloaded articles from Oral Diseases through last year (Figure 2, Table 2). The five top downloaded articles include ones on halitosis, oral sequelae of radiotherapy for head and neck cancer, hepatitis C, diabetes mellitus and salivary gland repair. These articles reflect subjects that are of real interest to those in the head and neck sciences, whether their focus is clinical or biological. The increasing popularity of Oral Diseases is further affirmed by a ∼50% increase in the number of manuscripts of all types submitted from January–August of this year compared to the same period last year, something that has resulted in an increase in the number of issues published this year from six to eight. Increase in online downloads from Oral Diseases 2002–2008 In 2005, we defined our mission statement as follows: ‘Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders. It seeks to provide a forum for addressing biological and clinical issues linked by this anatomical locale, thus bridging often-isolated concerns of dentistry and medicine. As such, Oral Diseases aims to foster integrative approaches to the understanding and management of oral and perioral conditions with particular reference to systemic implications.’ While much remains to be done, we are clearly heading towards realization of that goal. Oral Diseases has become the premier journal of Oral Medicine, and is making progress towards being a ‘must read’ journal for all head and neck sciences. We are slowly, in a small way, linking dentistry and oral diseases with general medicine, something we believe will greatly benefit many patients. We sincerely thank our authors, reviewers, Editorial Board and Associate Editors for making this happen.

The Dynamic Interest in Topics within the Biomedical Scientific Community

The increase in the size of the scientific community created an explosion in scientific production. We have analyzed the dynamics of biomedical scientific output during 1957–2007 by applying a bibliometric analysis of the PubMed database using different keywords representing specific biomedical topics. With the assumption that increased scientific interest will result in increased scientific output, we compared the output of specific topics to that of all scientific output. This analysis resulted in three broad categories of topics; those that follow the general trend of all scientific output, those that show highly variable output, and attractive topics which are new and grow explosively. The analysis of the citation impact of the scientific output resulted in a typical longtail distribution: the majority of journals and articles are of very low impact. This distribution has remained unchanged since 1957, although the interests of scientists must have shifted in this period. We therefore analyzed the distribution of articles in top journals and lower impact journals over time for the attractive topics. Novelty is rewarded by publication in top journals. Over time more articles are published in low impact journals progressively creating the longtail distribution, signifying acceptance of the topic by the community. There can be a gap of years between novelty and acceptance. Within topics temporary novelty is created with new subtopics. In conclusion, the longtail distribution is the foundation of the scientific output of the scientific community and can be used to examine different aspects of science practice.

Conference Scene: Wake-Up Call for The Engineering and Biomedical Science Communities in Nanomedicine

The IEEE-NIH 4th Life Science Systems and Applications Workshop 2009 (LiSSA '09) was jointly organized by the IEEE LiSSA Technical Committee and the NIH Nano Task Force. It was endorsed by the NIH Biomedical Information Science and Technology Initiative (BISTI) and the National Library of Medicine. The workshop was held in the Natcher Conference Center on the NIH campus in Bethesda, MD, USA. It took place on the 9-10 April, 2009, during the NIH NanoWeek and had approximately 200 delegates from around the globe (including North America, Europe, Asia and Australia) from both engineering and biomedical science disciplines. The conference featured around 40 talks, including nine plenary speakers emphasizing current state-of-the-art nanotechnology practices, developments and industry applications. All talks were scheduled in three oral and seven special sessions, as well as three breakout sessions. In addition, the interactive poster sessions hosted over 30 abstracts and attracted much attention from the audience; these sessions were readily used by many attendees to connect with colleagues of similar interest. In this article, we provide some of the highlights from the workshop.

A statement of the rights of scientists and engineers

As the Editors of the Biomedical Imaging and Intervention Journal, we are pleased to introduce “The Bill of Rights” written by Dr William Hendee, Chair of the Publication Committee of the International Organization of Medical Physics (IOMP). This document covers the fundamental rights and responsibilities of a scientist - not just medical physicists but the entire biomedical imaging community, including the clinicians and researchers. The simultaneous publication of this document in worldwide leading medical physics and allied journals aims to disseminate these standards to the whole scientific world. We, as part of the wider biomedical imaging science community and as the editors of the biij, are fully committed to ensuring these rights are not infringed by anyone, anywhere.BJJ Abdullah and KH NgEditors, Biomedical Imaging and Intervention Journal

A wake-up call for the engineering and biomedical science communities

With the burst of Information Technology (IT) bubble at the beginning of this century, people are looking for the next wave of technology in which to invest. While we believe that biomedical applications and systems are this next stage, unfortunately, the engineering and bioscience communities are unprepared for the many challenges. In order to connect the engineering and the biomedical science communities, we established the LifeScience Systems and Applications (LiSSA) Technical Committee within IEEE Circuits and Systems Society in 2005--an initiative supported by the National Institutes of Health (NIH) through a conference grant to enable dialogue between the engineering and biomedical science communities. Henceforth, we have organized several annual workshops with different themes on the NIH campus. After each workshop, a white paper is published in IEEE circuits and systems magazine to present the major challenges in various chosen theme areas. Recently, we chose "Biomarker Development and Applications" as our workshop theme. For the first time, we invited eight IEEE societies and various NIH institutes to send their representatives for face-to-face dialogue. This article presents the major challenges in biomarker development and applications based on the general consensus of the conference. The aim of the article is to serve as a wake-up call for more engineers to participate in crucial life-science application and systems research.

Promising trends of bioceramics in the biomaterials field

Biomedical scientific community is currently demanding new advances in the designing of 3rd generation bioceramics, which promote bone tissue regeneration. In the last years, the development of supramolecular chemistry and the application of organic-inorganic hybrid materials in the biomedical field have resulted in a new generation of advanced bioceramics, which exhibit fascinating properties for regenerative purposes together with the possibility of being used as carriers of biologically active molecules. This communication overviews the evolution occurred from the first silica based bioceramics to the last advances in the synthesis of bioceramics for bone tissue regeneration. A critical review concerning the first bioactive glasses as well as the newest hybrid bioactive materials and templated mesoporous bioactive systems, will be performed from the point of view of their potential applications as replacement materials in bone repair and regeneration.

Nanostructured Mesoporous Silicas for Bone Tissue Regeneration

The research on the development of new biomaterials that promote bone tissue regeneration is receiving great interest by the biomedical scientific community. Recent advances in nanotechnology have allowed the design of materials with nanostructure similar to that of natural bone. These materials can promote new bone formation by inducing the formation of nanocrystalline apatites analogous to the mineral phase of natural bone onto their surfaces, i.e. they are bioactive. They also stimulate osteoblast proliferation and differentiation and, therefore, accelerate the healing processes. Silica‐based ordered mesoporous materials are excellent candidates to be used as third generation bioceramics that enable the adsorption and local control release of biological active agents that promote bone regeneration. This local delivery capability together with the bioactive behavior of mesoporous silicas opens up promising expectations in the bioclinical field. In this review, the last advances in nanochemistry aimed at designing and tailoring the chemical and textural properties of mesoporous silicas for biomedical applications are described. The recent developed strategies to synthesize bioactive glasses with ordered mesopore arrangements are also summarized. Finally, a deep discussion about the influence of the textural parameters and organic modification of mesoporous silicas on molecules adsorption and controlled release is performed.

A statement of the rights of scientists and engineers

As the Editors of the Biomedical Imaging and Intervention Journal, we are pleased to introduce Bill of Rights written by Dr William Hendee, Chair of the Publication Committee of the International Organization of Medical Physics (IOMP). This document covers the fundamental rights and responsibilities of a scientist - not just medical physicists but the entire biomedical imaging community, including the clinicians and researchers. The simultaneous publication of this document in worldwide leading medical physics and allied journals aims to disseminate these standards to the whole scientific world. We, as part of the wider biomedical imaging science community and as the editors of the biij, are fully committed to ensuring these rights are not infringed by anyone, anywhere.BJJ Abdullah and KH NgEditors, Biomedical Imaging and Intervention Journal.

Gallus Expression In Situ Hybridization Analysis: A Chicken Embryo Gene Expression Database

With sequencing of the chicken genome largely completed, significant effort is focusing on gene annotation, including acquiring information about the patterns of gene expression. The chicken embryo is ideally suited to provide detailed temporal and spatial expression information through in situ hybridization gene expression analysis in vivo. We have developed the Gallus expression in situ hybridization analysis (GEISHA) database and user interface (http://geisha.arizona.edu) to serve as a centralized repository of in situ hybridization photos and metadata from chicken embryos. This report describes the design and implementation the GEISHA database and Web site and illustrates its usefulness for researchers in the biomedical and poultry science communities. Results from a recent comprehensive expression analysis of microRNA expression in chicken embryos are also presented.