BackgroundTendon disorders (tendinopathies) pose serious biomedical and socioeconomic problems. Despite diverse treatment approaches, the best treatment strategy remains unclear. Surgery remains the last resort because of the associated morbidity and inconsistent outcomes. We hypothesized that, similar to fibroblasts in various organs, tendon fibroblasts (tenocytes) might be responsive to stimulation with interleukins (ILs), particularly IL-4 and IL-13. These two cytokines share sequence homology, receptor chains and functional effects, including stimulation of fibrogenesis. It is unknown whether tenocytes are responsive to stimulation with IL-4 or IL-13. If true, local use of these cytokines might be used to facilitate tendon repair in patients with tendinopathies or used for tendon tissue-engineering approaches to facilitate tenocyte growth on scaffolds in culture.ResultsTendon tissues that would normally be discarded were obtained during reconstructive surgery procedures performed for clinical indications. Primary tenocytes were derived from Achilles, posterior tibial, flexor digitorum longus and flexor hallucis longus tendon tissue samples. Reverse transcriptase quantitative PCR (RT-qPCR) experiments revealed that mRNAs for the receptor (R) chains IL-4Rα, IL-13Rα1 and IL-13Rα2, but not the common γ-chain were present in all tested tendon tissues and in cultured tenocytes. Levels of IL-13R chain mRNAs were significantly higher than those of IL-4R mRNA. The cultures responded, in a dose-dependent fashion, to stimulation with recombinant human IL-4 or IL-13, by increasing proliferation rates 1.5 to 2.0-fold. The mRNA levels of 84 genes related to cell cycle regulation were measured by RT-qPCR after 6 h and 24 h of activation. The expression levels of several genes, notably CDK6 and CDKN2B changed more than twofold. In contrast to their effects on proliferation, stimulation with IL-4 or IL-13 had little if any effect on the levels of collagen mRNA or protein in cultured primary tenocytes. The mRNA levels of 84 other genes related to extracellular matrix and cell adhesion were also measured by RT-qPCR; expression of only five genes was consistently changed.ConclusionsStimulation with IL-4 or IL-13 could be used to facilitate tendon repair in vivo or to aid in tendon tissue engineering, through stimulation of tenocyte proliferation.

Background: Little has been reported about the biologic effect of shock waves on human normal or pathologic tendon tissue. We hypothesized that inflammatory cytokine and MMP production would be down-regulated by shock wave stimulation. . IL-6 levels were higher in the diseased tenocytes as compared with normal tenocytes (44.10 ± 16.72 versus 0.21 ± 0.55 ng/ml, (p < 0.05). IL-1 levels in normal cells increased (2.24 ± 5.02 ng/ml to 9.31 ± 6.85 ng/ml) after shock wave treatment (p = 0.04). In diseased tenocytes, levels of MMP-1 (1.12 ± 0.23 to 0.75 ± 0.24 ng/ml; p = 0.04) and MMP-13 (1.43 ± 0.11 to 0.80 ± 0.15 ng/ml; p = 0.04) were significantly decreased after shock wave treatment. The IL-6 level in diseased tenocytes was decreased (44.10 ± 16.72 to 14.66 ±

Despite having an ideal setup in their labs for wet work, researchers often lack the computational infrastructure to analyze the magnitude of data that result from “-omics” experiments. In this innovative project, the library supports analysis of high-throughput data from global molecular profiling experiments by offering a high-performance computer with open source software along with expert bioinformationist support. The audience for this new service is faculty, staff, and students for whom using the university’s large scale, CORE computational resources is not warranted because these resources exceed the needs of smaller projects. In the library’s approach, users are empowered to analyze high-throughput data that they otherwise would not be able to on their own computers. To develop the project, the library’s bioinformationist identified the ideal computing hardware and a group of open source bioinformatics software to provide analysis options for experimental data such as scientific images, sequence reads, and flow cytometry files. To close the loop between learning and practice, the bioinformationist developed self-guided learning materials and workshops or consultations on topics such as the National Center for Biotechnology Information’s BLAST, Bioinformatics on the Cloud, and ImageJ. Researchers apply the data analysis techniques that they learned in the classroom in the library’s ideal computing environment.

Response Gene to Complement 32 (RGC-32) is an important mediator of the TGF-β signaling pathway, and an increasing amount of evidence implicates this protein in regulating astrocyte biology. We showed recently that spinal cord astrocytes in mice lacking RGC-32 display an immature phenotype reminiscent of progenitors and radial glia, with an overall elongated morphology, increased proliferative capacity, and increased expression of progenitor markers when compared to their wild-type (WT) counterparts that make them incapable of undergoing reactive changes during the acute phase of experimental autoimmune encephalomyelitis (EAE). Here, in order to decipher the molecular networks underlying RGC-32’s ability to regulate astrocytic maturation and reactivity, we performed next-generation sequencing of RNA from WT and RGC-32 knockout (KO) neonatal mouse brain astrocytes, either unstimulated or stimulated with the pleiotropic cytokine TGF-β. Pathway enrichment analysis showed that RGC-32 is critical for the TGF-β-induced up-regulation of transcripts encoding proteins involved in brain development and tissue remodeling, such as axonal guidance molecules, transcription factors, extracellular matrix (ECM)-related proteins, and proteoglycans. Our next-generation sequencing of RNA analysis also demonstrated that a lack of RGC-32 results in a significant induction of WD repeat and FYVE domain-containing protein 1 (Wdfy1) and stanniocalcin-1 (Stc1). Immunohistochemical analysis of spinal cords isolated from normal adult mice and mice with EAE at the peak of disease showed that RGC-32 is necessary for the in vivo expression of ephrin receptor type A7 in reactive astrocytes, and that the lack of RGC-32 results in a higher number of homeodomain-only protein homeobox (HOPX)+ and CD133+ radial glia cells. Collectively, these findings suggest that RGC-32 plays a major role in modulating the transcriptomic changes in astrocytes that ultimately lead to molecular programs involved in astrocytic differentiation and reactive changes during neuroinflammation.

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Biomedical text mining promises to assist biologists in quickly navigating the combined knowledge in their domain. This would allow improved understanding of the complex interactions within biological systems and faster hypothesis generation. New biomedical research articles are published daily and text mining tools are only as good as the corpus from which they work. Many text mining tools are underused because their results are static and do not reflect the constantly expanding knowledge in the field. In order for biomedical text mining to become an indispensable tool used by researchers, this problem must be addressed. To this end, we present PubRunner, a framework for regularly running text mining tools on the latest publications.

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