Discovering context-specific relationships from biological literature by using multi-level context terms

<p>Abstract</p> <p>Background</p> <p>The Swanson's ABC model is powerful to infer hidden relationships buried in biological literature. However, the model is inadequate to infer relations with context information. In addition, the model generates a very large amount of candidates from biological text, and it is a semi-automatic, labor-intensive technique requiring human expert's manual input. To tackle these problems, we incorporate context terms to infer relations between AB interactions and BC interactions.</p> <p>Methods</p> <p>We propose 3 steps to discover meaningful hidden relationships between drugs and diseases: 1) multi-level (gene, drug, disease, symptom) entity recognition, 2) interaction extraction (drug-gene, gene-disease) from literature, 3) context vector based similarity score calculation. Subsequently, we evaluate our hypothesis with the datasets of the "Alzheimer's disease" related 77,711 PubMed abstracts. As golden standards, PharmGKB and CTD databases are used. Evaluation is conducted in 2 ways: first, comparing precision of the proposed method and the previous method and second, analysing top 10 ranked results to examine whether highly ranked interactions are truly meaningful or not.</p> <p>Results</p> <p>The results indicate that context-based relation inference achieved better precision than the previous ABC model approach. The literature analysis also shows that interactions inferred by the context-based approach are more meaningful than interactions by the previous ABC model.</p> <p>Conclusions</p> <p>We propose a novel interaction inference technique that incorporates context term vectors into the ABC model to discover meaningful hidden relationships. By utilizing multi-level context terms, our model shows better performance than the previous ABC model.</p

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

TCMGeneDIT: a database for associated traditional Chinese medicine, gene and disease information using text mining

<p>Abstract</p> <p>Background</p> <p>Traditional Chinese Medicine (TCM), a complementary and alternative medical system in Western countries, has been used to treat various diseases over thousands of years in East Asian countries. In recent years, many herbal medicines were found to exhibit a variety of effects through regulating a wide range of gene expressions or protein activities. As available TCM data continue to accumulate rapidly, an urgent need for exploring these resources systematically is imperative, so as to effectively utilize the large volume of literature.</p> <p>Methods</p> <p>TCM, gene, disease, biological pathway and protein-protein interaction information were collected from public databases. For association discovery, the TCM names, gene names, disease names, TCM ingredients and effects were used to annotate the literature corpus obtained from PubMed. The concept to mine entity associations was based on hypothesis testing and collocation analysis. The annotated corpus was processed with natural language processing tools and rule-based approaches were applied to the sentences for extracting the relations between TCM effecters and effects.</p> <p>Results</p> <p>We developed a database, TCMGeneDIT, to provide association information about TCMs, genes, diseases, TCM effects and TCM ingredients mined from vast amount of biomedical literature. Integrated protein-protein interaction and biological pathways information are also available for exploring the regulations of genes associated with TCM curative effects. In addition, the transitive relationships among genes, TCMs and diseases could be inferred through the shared intermediates. Furthermore, TCMGeneDIT is useful in understanding the possible therapeutic mechanisms of TCMs via gene regulations and deducing synergistic or antagonistic contributions of the prescription components to the overall therapeutic effects. The database is now available at <url>http://tcm.lifescience.ntu.edu.tw/</url>.</p> <p>Conclusion</p> <p>TCMGeneDIT is a unique database that offers diverse association information on TCMs. This database integrates TCMs with biomedical studies that would facilitate clinical research and elucidate the possible therapeutic mechanisms of TCMs and gene regulations.</p

The effectiveness of injury prevention programs to modify risk factors for non-contact anterior cruciate ligament and hamstring injuries in uninjured team sports athletes: A systematic review

Background Hamstring strain and anterior cruciate ligament injuries are, respectively, the most prevalent and serious non-contact occurring injuries in team sports. Specific biomechanical and neuromuscular variables have been used to estimate the risk of incurring a non-contact injury in athletes. Objective The aim of this study was to systematically review the evidences for the effectiveness of injury prevention protocols to modify biomechanical and neuromuscular anterior cruciate and/or hamstring injuries associated risk factors in uninjured team sport athletes. Data Sources PubMed, Science Direct, Web of Science, Cochrane Libraries, U.S. National Institutes of Health clinicaltrials.gov, Sport Discuss and Google Scholar databases were searched for relevant journal articles published until March 2015. A manual review of relevant articles, authors, and journals, including bibliographies was performed from identified articles. Main Results Nineteen studies were included in this review. Four assessment categories: i) landing, ii) side cutting, iii) stop-jump, and iv) muscle strength outcomes, were used to analyze the effectiveness of the preventive protocols. Eight studies using multifaceted interventions supported by video and/or technical feedback showed improvement in landing and/or stop-jump biomechanics, while no effects were observed on side-cutting maneuver. Additionally, multifaceted programs including hamstring eccentric exercises increased hamstring strength, hamstring to quadriceps functional ratio and/or promoted a shift of optimal knee flexion peak torque toward a more open angle position. Conclusions Multifaceted programs, supported by proper video and/or technical feedback, including eccentric hamstring exercises would positively modify the biomechanical and or neuromuscular anterior cruciate and/or hamstring injury risk factors

The SPINK gene family and celiac disease susceptibility

The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was determined for all four SPINK genes by quantitative reverse-transcription polymerase chain reaction in duodenal biopsy samples from untreated (n = 15) and diet-treated patients (n = 31) and controls (n = 16). Genetic association of the four SPINK genes was tested within a total of 18 haplotype tagging SNPs, one coding SNP, 310 patients, and 180 controls. The SPINK4 study cohort was further expanded to include 479 CD cases and 540 controls. SPINK4 DNA sequence analysis was performed on six members of a multigeneration CD family to detect possible point mutations or deletions. SPINK4 showed differential gene expression, which was at its highest in untreated patients and dropped sharply upon commencement of a gluten-free diet. Genetic association tests for all four SPINK genes were negative, including SPINK4 in the extended case/control cohort. No SPINK4 mutations or deletions were observed in the multigeneration CD family with linkage to chromosome 9p21-13 nor was the coding SNP disease-specific. SPINK4 exhibits CD pathology-related differential gene expression, likely derived from altered goblet cell activity. All of the four SPINK genes tested do not contribute to the genetic risk for CD in the Dutch population

Sobolev spaces on non-Lipschitz subsets of Rn with application to boundary integral equations on fractal screens

We study properties of the classical fractional Sobolev spaces on non-Lipschitz subsets of Rn. We investigate the extent to which the properties of these spaces, and the relations between them, that hold in the well-studied case of a Lipschitz open set, generalise to non-Lipschitz cases. Our motivation is to develop the functional analytic framework in which to formulate and analyse integral equations on non-Lipschitz sets. In particular we consider an application to boundary integral equations for wave scattering by planar screens that are non-Lipschitz, including cases where the screen is fractal or has fractal boundary

Notch Signaling Regulates Late-Stage Epidermal Differentiation and Maintains Postnatal Hair Cycle Homeostasis

Notch signaling involves ligand-receptor interactions through direct cell-cell contact. Multiple Notch receptors and ligands are expressed in the epidermis and hair follicles during embryonic development and the adult stage. Although Notch signaling plays an important role in regulating differentiation of the epidermis and hair follicles, it remains unclear how Notch signaling participates in late-stage epidermal differentiation and postnatal hair cycle homeostasis.We applied Cre/loxP system to generate conditional gene targeted mice that allow inactivation of critical components of Notch signaling pathway in the skin. Rbpj, the core component of all four Notch receptors, and Pofut1, an essential factor for ligand-receptor interactions, were inactivated in hair follicle lineages and suprabasal layer of the epidermis using the Tgfb3-Cre mouse line. Rbpj conditional inactivation resulted in granular parakeratosis and reactive epidermal hyperplasia. Pofut1 conditional inactivation led to ultrastructural abnormalities in the granular layer and altered filaggrin processing in the epidermis, suggesting a perturbation of the granular layer differentiation. Disruption of Pofut1 in hair follicle lineages resulted in aberrant telogen morphology, a decrease of bulge stem cell markers, and a concomitant increase of K14-positive keratinocytes in the isthmus of mutant hair follicles. Pofut1-deficent hair follicles displayed a delay in anagen re-entry and dysregulation of proliferation and apoptosis during the hair cycle transition. Moreover, increased DNA double stand breaks were detected in Pofut1-deficent hair follicles, and real time PCR analyses on bulge keratinocytes isolated by FACS revealed an induction of DNA damage response and a paucity of DNA repair machinery in mutant bulge keratinocytes.our data reveal a role for Notch signaling in regulating late-stage epidermal differentiation. Notch signaling is required for postnatal hair cycle homeostasis by maintaining proper proliferation and differentiation of hair follicle stem cells

Astrocytes: biology and pathology

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions

Cyanobacterial lipopolysaccharides and human health – a review

Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the cyanobacteria literature as toxins responsible for a variety of heath effects in humans, from skin rashes to gastrointestinal, respiratory and allergic reactions. The attribution of toxic properties to cyanobacterial LPS dates from the 1970s, when it was thought that lipid A, the toxic moiety of LPS, was structurally and functionally conserved across all Gram-negative bacteria. However, more recent research has shown that this is not the case, and lipid A structures are now known to be very different, expressing properties ranging from LPS agonists, through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is widely cited as a putative toxin, most of the small number of formal research reports describe cyanobacterial LPS as weakly toxic compared to LPS from the Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial LPS, and also examined the much lager body of literature relating to heterotrophic bacterial LPS and the atypical lipid A structures of some photosynthetic bacteria. While the literature on the biological activity of heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to review for the purposes of exclusion, we were unable to find a convincing body of evidence to suggest that heterotrophic bacterial LPS, in the absence of other virulence factors, is responsible for acute gastrointestinal, dermatological or allergic reactions via natural exposure routes in humans. There is a danger that initial speculation about cyanobacterial LPS may evolve into orthodoxy without basis in research findings. No cyanobacterial lipid A structures have been described and published to date, so a recommendation is made that cyanobacteriologists should not continue to attribute such a diverse range of clinical symptoms to cyanobacterial LPS without research confirmation