Body segment parameters of Paralympic athletes from dual-energy X-ray absorptiometry

The final publication is available at Springer via http://dx.doi.org/10.1007/s12283-016-0200-3This research represents the first documented investigation into the body segment parameters of Paralympic athletes (e.g., individuals with spinal cord injuries and lower extremity amputations). Two-dimensional body segment parameters (i.e., mass, length, position vector of the center of mass, and principal mass moment of inertia about the center of mass) were quantified from dual-energy X-ray absorptiometry (DXA). In addition to establishing a body segment parameter database of Paralympic athletes for prospective biomechanists and engineers, the mass of each body segment as experimentally measured via the DXA imaging was compared with that reported by previous research of able-bodied cadavers. In general, there were significant differences in the body segment masses between the different methods. These findings support the implementation of the proposed database for developing valid multibody biomechanical models of Paralympic athletes with distinct physical disabilities.This research was funded by Dr. John McPhee’s Tier I Canada Research Chair in Biomechatronic System Dynamics

Diagnostic Accuracy of Fine Needle Biopsy for Metastatic Melanoma and Its Implications for Patient Management

The use of fine needle biopsy (FNB) for the diagnosis of metastatic melanoma can lead to the early removal and treatment of metastases, reduce the frequency of unnecessary surgery, and facilitate the staging of patients enrolled in clinical trials of adjuvant therapies. In this study, the accuracy of FNB for the diagnosis of metastatic melanoma was investigated. A retrospective cohort study was performed with 2204 consecutive FNBs performed on 1416 patients known or suspected to have metastatic melanoma. Almost three-quarters (1582) of these FNBs were verified by either histopathologic diagnosis following surgical resection or clinical follow-up. FNB for metastatic melanoma was found to have an overall sensitivity of 92.1% and a specificity of 99.2%, with 69 false-negative and 5 false-positive findings identified. The sensitivity of the procedure was found to be influenced by six factors. The use of immunostains, reporting of the specimen by a cytopathologist who had reported >500 cases, lesions located in the skin and subcutis, and patients with ulcerated primary melanomas were factors associated with a significant improvement in the sensitivity of the test. However, FNBs performed in masses located in lymph nodes of the axilla and FNBs that required more than one needle pass to obtain a sample were far more likely to result in false-negative results. FNB is a rapid, accurate, and clinically useful technique for the assessment of disease status in patients with suspected metastatic melanoma

Impairment of germline transmission after blastocyst injection with murine embryonic stem cells cultured with mouse hepatitis virus and mouse minute virus

The aim of this study was to determine the susceptibility of murine embryonic stem (mESCs) to mouse hepatitis virus (MHV-A59) and mouse minute virus (MMVp) and the effect of these viruses on germline transmission (GLT) and the serological status of recipients and pups. When recipients received 10 blastocysts, each injected with 100 TCID50 MHV-A59, three out of five recipients and four out of 14 pups from three litters became seropositive. When blastocysts were injected with 10−5 TCID50 MMVp, all four recipients and 14 pups from four litters remained seronegative. The mESCs replicated MHV-A59 but not MMVp, MHV-A59 being cytolytic for mESCs. Exposure of mESCs to the viruses over four to five passages but not for 6 h affected GLT. Recipients were seropositive for MHV-A59 but not for MMVp when mESCs were cultured with the virus over four or five passages. The data show that GLT is affected by virus-contaminated mESCs

Challenges for automatically extracting molecular interactions from full-text articles

<p>Abstract</p> <p>Background</p> <p>The increasing availability of full-text biomedical articles will allow more biomedical knowledge to be extracted automatically with greater reliability. However, most Information Retrieval (IR) and Extraction (IE) tools currently process only abstracts. The lack of corpora has limited the development of tools that are capable of exploiting the knowledge in full-text articles. As a result, there has been little investigation into the advantages of full-text document structure, and the challenges developers will face in processing full-text articles.</p> <p>Results</p> <p>We manually annotated passages from full-text articles that describe interactions summarised in a Molecular Interaction Map (MIM). Our corpus tracks the process of identifying facts to form the MIM summaries and captures any factual dependencies that must be resolved to extract the fact completely. For example, a fact in the results section may require a synonym defined in the introduction. The passages are also annotated with negated and coreference expressions that must be resolved.</p> <p>We describe the guidelines for identifying relevant passages and possible dependencies. The corpus includes 2162 sentences from 78 full-text articles. Our corpus analysis demonstrates the necessity of full-text processing; identifies the article sections where interactions are most commonly stated; and quantifies the proportion of interaction statements requiring coherent dependencies. Further, it allows us to report on the relative importance of identifying synonyms and resolving negated expressions. We also experiment with an oracle sentence retrieval system using the corpus as a gold-standard evaluation set.</p> <p>Conclusion</p> <p>We introduce the MIM corpus, a unique resource that maps interaction facts in a MIM to annotated passages within full-text articles. It is an invaluable case study providing guidance to developers of biomedical IR and IE systems, and can be used as a gold-standard evaluation set for full-text IR tasks.</p

Network Modeling Identifies Molecular Functions Targeted by miR-204 to Suppress Head and Neck Tumor Metastasis

Due to the large number of putative microRNA gene targets predicted by sequence-alignment databases and the relative low accuracy of such predictions which are conducted independently of biological context by design, systematic experimental identification and validation of every functional microRNA target is currently challenging. Consequently, biological studies have yet to identify, on a genome scale, key regulatory networks perturbed by altered microRNA functions in the context of cancer. In this report, we demonstrate for the first time how phenotypic knowledge of inheritable cancer traits and of risk factor loci can be utilized jointly with gene expression analysis to efficiently prioritize deregulated microRNAs for biological characterization. Using this approach we characterize miR-204 as a tumor suppressor microRNA and uncover previously unknown connections between microRNA regulation, network topology, and expression dynamics. Specifically, we validate 18 gene targets of miR-204 that show elevated mRNA expression and are enriched in biological processes associated with tumor progression in squamous cell carcinoma of the head and neck (HNSCC). We further demonstrate the enrichment of bottleneckness, a key molecular network topology, among miR-204 gene targets. Restoration of miR-204 function in HNSCC cell lines inhibits the expression of its functionally related gene targets, leads to the reduced adhesion, migration and invasion in vitro and attenuates experimental lung metastasis in vivo. As importantly, our investigation also provides experimental evidence linking the function of microRNAs that are located in the cancer-associated genomic regions (CAGRs) to the observed predisposition to human cancers. Specifically, we show miR-204 may serve as a tumor suppressor gene at the 9q21.1–22.3 CAGR locus, a well established risk factor locus in head and neck cancers for which tumor suppressor genes have not been identified. This new strategy that integrates expression profiling, genetics and novel computational biology approaches provides for improved efficiency in characterization and modeling of microRNA functions in cancer as compared to the state of art and is applicable to the investigation of microRNA functions in other biological processes and diseases

Mysid crustaceans as standard models for the screening and testing of endocrine-disrupting chemicals

Author Posting. © Springer, 2007. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ecotoxicology 16 (2007): 205-219, doi:10.1007/s10646-006-0122-0.Investigative efforts into the potential endocrine-disrupting effects of chemicals have mainly concentrated on vertebrates, with significantly less attention paid to understanding potential endocrine disruption in the invertebrates. Given that invertebrates account for at least 95% of all known animal species and are critical to ecosystem structure and function, it remains essential to close this gap in knowledge and research. The lack of progress regarding endocrine disruption in invertebrates is still largely due to: (1) our ignorance of mode-of-action, physiological control, and hormone structure and function in invertebrates; (2) lack of a standardized invertebrate assay; (3) the irrelevance to most invertebrates of the proposed activity-based biological indicators for endocrine disruptor exposure (androgen, estrogen and thyroid); (4) limited field studies. Past and ongoing research efforts using the standard invertebrate toxicity test model, the mysid shrimp, have aimed at addressing some of these issues. The present review serves as an update to a previous publication on the use of mysid shrimp for the evaluation of endocrine disruptors (Verslycke et al., 2004a). It summarizes recent investigative efforts that have significantly advanced our understanding of invertebrate-specific endocrine toxicity, population modeling, field studies, and transgeneration standard test development using the mysid model.Supported by a Fellowship of the Belgian American Educational Foundation

Effects of bovine follicular fluid and partially purified bovine inhibin on FSH and LH release by bovine pituitary cells in culture

International audienc

Laminin receptor 1 is differentially expressed in thoracic and limb wounds in the horse

Healing of wounds located on the distal limbs of horses is often complicated by retarded epithelialization and the development of exuberant granulation tissue (proud flesh). Treatments that definitively resolve this pathological process are still unavailable. Molecular studies of the repair mechanism might contribute to the development of new therapeutic strategies. The study presented herein aimed to clone the full length cDNA and to study the spatio-temporal expression profile of mRNA and protein for LAMR1, previously attributed a role in wound epithelialization, during the repair of body and limb wounds in the horse. Cloning was achieved by screening a cDNA library previously derived from 7-day wound biopsies. Expression was studied in unwounded skin and in samples from 1-, 2-, 3-, 4- and 6-week-old wounds of the body and limb. Temporal gene expression was determined by real time polymerase chain reaction (RT-PCR) while protein expression was mapped immunohistochemically. Full-length cDNA for equine LAMR1 was shown to be highly similar to that of other species. The mRNA expression of LAMR1 was significantly up-regulated only in thoracic wounds, 4 and 6 weeks following wounding (upon epithelialization). Cutaneous wounding induced protein expression at both locations. Our data suggest that up-regulation of LAMR1 protein might favour epithelialization during wound healing. However, its interaction with ligands other than laminin complicates data interpretation. Future studies should quantitatively verify the temporal expression of this protein in order to provide the basis for targeted therapies that might enhance epithelialization

Equine lumican (LUM) cDNA sequence and spatio-temporal expression in an experimental model of normal and pathological wound healing

The development of exuberant granulation tissue, a situation that in some ways resembles the human keloid, compromises both the aesthetic and functional outcomes of wound repair in horses. To help elucidate the underlying molecular mechanisms the spatio-temporal expression of lumican (LUM) mRNA and protein for their potential contributions to tissue remodelling of body and limb wounds, was examined in an established experimental model. Expression was studied in intact skin and in samples of 1-, 2-, 3-, 4- and 6-week-old wounds of the body and forelimb. Temporal gene expression was determined by reverse transcriptase polymerase chain reaction, and protein expression was mapped immunohistochemically. A significant increase in LUM mRNA expression was observed in response to wounding at both anatomical locations, and a significantly higher mRNA level was recorded in thoracic than in limb wounds at weeks 1, 3 and 6 of repair. The immunohistochemical observations partially corroborated the mRNA data. To the authors' knowledge this study is the first to document that the cDNA for LUM is expressed over the different phases of wound repair in horses and suggests that LUM might be involved in both inflammation and remodelling in response to dermal injury. Further studies are now required to verify and quantify the temporal expression of this protein to provide the basis for targeted therapies that might prevent the development of exuberant granulation tissue in horse wound repair

Equine ANXA2 and MMP1 expression analyses in an experimental model of normal and pathological wound repair.

BACKGROUND: Wounds on horse limbs can develop exuberant granulation tissue which resembles the human keloid. Clues gained from the study of over-scarring in horses might help control fibro-proliferative disorders. OBJECTIVES: The aim of the present study was to clone full-length equine ANXA2 cDNA then to study spatio-temporal expression of ANXA2 and MMP1 mRNA and protein, potential contributors to remodeling, during repair of body (normal) and limb (fibro-proliferative) wounds in an established horse wound model. METHODS: Cloning of ANXA2 was achieved by screening size-selected cDNA libraries. Expression was studied in intact skin and in biopsies of 1, 2, 3, 4 and 6-week-old wounds of the body and limb. Temporal gene expression was determined by semi-quantitative RT-PCR while protein expression was mapped immunohistochemically. RESULTS: ANXA2 mRNA was up-regulated only in body wounds, corroborating the superior and prompt tissue turnover at this location. Immunohistochemistry partially substantiated the mRNA data in that increased staining for ANXA2 protein was detected in neo-epidermis which formed more rapidly and completely in body wounds. MMP1 mRNA levels in body wounds significantly surpassed those of limb wounds in week one biopsies. The protein was abundant in migrating epithelium of limb wounds at weeks two and four; conversely, body wounds in which epithelialization was near complete showed diminished staining of MMP1. CONCLUSION: We conclude that ANXA2 and MMP1 might participate in remodeling during wound healing in the horse, and that differences in expression may contribute to the excessive proliferative response seen in the limb