1,720,969 research outputs found
Induction of Hypertrophy in Human Cartilage Endplate Cells Promotes Angiogenesis and Catabolism in the Intervertebral Disc
Get PDF2017 Denman Undergraduate Research Forum Winner. First PlaceLow back pain is second only to cancer in terms of socioeconomic burden in the U.S., but current treatments are highly invasive and fail to target the underlying cellular mechanisms of intervertebral disc (IVD) degeneration. In degeneration, the cartilaginous end plate (CEP) becomes calcified, however the mechanisms are not well understood. In diseases such as osteoarthritis, a proposed mechanism is the recapitulation of developmental processes and we suggest that in degeneration, CEP cells undergo hypertrophic differentiation similar to endochondral ossification. The aim of this study was to determine if CEP cells can undergo hypertrophic differentiation, leading to angiogenesis. Human CEP cells (hCEPs) were isolated from autopsy and pellet cultured. For 21 days, pellets were cultured in either chondrogenic or hypertrophic (10% FBS or CHIR99021, a wnt agonist) media in 5% oxygen, after which samples were used for viability, histology, qRT-PCR, DMMB proteoglycan assay, and generation of conditioned media (CM). Soluble factors from CM generated after 21 days was pooled, and a HUVEC tubular formation assay ran. Tubular length was assessed using Image J plug in, Angiogensis Analyzer. No significant decreases in viability were seen in the chondrogenic control group. QRT-PCR showed a decrease of chondrogenic marker, COL2, in both hypertrophy groups compared to the chondrogenic group. Hypertrophic markers MMP13 and IHH displayed increases in the hypertrophy groups. Increases were also seen in the angiogenic and pain related markers, VEGF-A, TAC1, and NGF in the hypertrophy groups. DMMB assay and histological results show decreases in proteoglycans in the hypertrophy groups. HUVEC tubular formation assay showed that both hypertrophy groups increased the total length of tubules. This study sought to determine the underlying cellular mechanisms of low back pain and suggests that human CEPs have the ability to undergo hypertrophic differentiation similar to articular chondrocytes during OA, with subsequent angiogenesis and neoinnervation, and may be implicated in the process of IVD degeneration.No embargoAcademic Major: Biomedical Engineerin
Non-Viral Reprogramming of Diseased Intervertebral Disc Cells via Engineered Extracellular Vesicles reverts Pathogenesis of Low Back Pain: An In-Vivo Study
No full textEngineering: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)A five-year embargo was granted for this item
Nonviral transfection with Brachyury reprograms human intervertebral disc cells to a pro-anabolic anti-catabolic/inflammatory phenotype: A proof of concept study
No full textEngineering: 3rd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)Intervertebral disc (IVD) degeneration is a major contributor to chronic low back pain and is characterized by decreases in cellularity and proteoglycan synthesis, upregulation of matrix degradation, and increases in pro-inflammatory factors with neurovascular invasion. Current treatments fail to target the underlying pathology or promote tissue repair and approaches such as viral transfection raise safety concerns due to mutagenesis and unwarranted immune responses. To avoid such concerns, nonviral transfection is a viable method of gene delivery into the host cell while bypassing the caveats of viral delivery. Brachyury is expressed in the developing notochord and is associated with an immature healthy nucleus pulposus (NP). We hypothesize that Brachyury can reprogram degenerate NP cells to a healthy pro-anabolic phenotype with increased proteoglycan synthesis and decreased expression of catabolic, inflammatory and neurovascular markers. NP cells obtained from human autopsy (non-painful) and surgical tissues (painful) were transfected with plasmids encoding for Brachyury or an empty vector control via bulk electroporation. Post transfection, cells were seeded in 3D agarose constructs cultured over 4 weeks and analyzed for viability, gene expression, and proteoglycan. Results demonstrated successful transfection of both non-painful and painful NP cells. We observed long term Brachyury expression, significant increased expression of NP phenotypic markers FOXF1, KRT19, and chondrogenic marker SOX9 with decreases in inflammatory cytokines IL1-β/IL6, NGF, and MMPs and significant increase in proteoglycan synthesis. These results highlight nonviral transfection with developmental transcription factors, such as Brachyury, as a promising method to reprogram degenerate disc cells towards a healthy NP phenotype.A five-year embargo was granted for this item
Intervertebral disc Degeneration: The Role of Nucleus Pulposus cell/Neural cell Interaction
No full textAn association between painful lumbar intervertebral discs (IVDs) and innervation deep with the nucleus pulposus (NP) of the degenerate IVD has been highlighted by a number of studies. However the mechanisms responsible for driving this innervation and hence the pathogenesis of symptomatic IVD degeneration is complex. The extracellular matrix (ECM) component aggrecan has been shown to inhibit neurite outgrowth and a role for cell mteractions via the e production of soluble mediators from degenerate disc cells, hypothesised to be neurotrophic factors, has been proposed. This study was undertaken to investigate NP cell/neural cell interactions in relation to degeneration of the IVD.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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