1,720,998 research outputs found
Elucidating the Relationship Between Macrophages and Synovial Mesenchymal Progenitor Cell Chondrogenesis
No full textOsteoarthritis (OA) is a complex disease affecting articular cartilage and joint tissues. Macrophages in OA synovium contribute to the inflamed joint environment by releasing inflammatory mediators promoting cartilage loss. What remains unknown is how macrophages interact with synovial mesenchymal progenitor cells (sMPCs) in the joint. sMPCs are able to differentiate into cartilage but for unknown reasons, sMPC chondrogenic capacity is lost in OA. This thesis elucidates the relationship between macrophages and sMPC using synovial explants obtained from OA and normal patients. I found that altered macrophage activity (through cytokine stimulation and/or macrophage depletion) differentially regulates the chondrogenic capacity of sMPCs in a patient-specific manner. Also, the secretory profile of the explant is different between normal and OA patients in response to treatment. Taken together, there is heterogeneity within the responses of the OA patients, highlighting the need for personalized approaches to repair the cartilage within the OA joint
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Developing a novel biomimetic bioreactor for bone graft engineering with murine embryonic stem cells
No full textBibliography: p. 79-82Many pages are in colour.Following blood, bone graft transplantation is the second most common tissue transplant. Although tissue engineering holds great potential to fulfill demands for better treatment outcomes, it remains technologically challenging to produce bone grafts with normal physiological properties. During skeletal development, endochondral ossification initiates long bone formation and fracture healing. In this study, I aimed to build an in-vitro biomimetic bioreactor to recapitulate physiological niches and processes essential for endochondral ossification to grow bone tissues with anatomical and mechanical properties similar to the native tissues. Here, I have built a prototype capable of generating a dynamic cultivation environment and producing an ivory-toned construct with a stiff texture. The engineered construct greatly resembles a hyaline cartilage model undergoing initial stages of endochondral ossification during skeletal development. In the future, a possible engineered vasculature system may be integrated into the existing bioreactor design to enhance further maturation of constructs to form compact bone
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Exploring the Unique and Shared Proteolytic Properties of Calpain-1 and Calpain-2
No full textCalpain-1 (µ-calpain) and calpain-2 (m-calpain) are ubiquitous Ca²⁺-dependent cysteine proteases with overlapping and divergent roles in human cells that remain incompletely defined. This research leverages a genetic knockout model in HCT116 colon-carcinoma cells, coupled with proteomics and immunofluorescence microscopy, to chart the substrate landscapes of each isoform and relate proteolysis to subcellular distribution. Wild-type, CAPN1-/- and CAPN2-/- lines were incubated with a calcium ionophore to permit acute calpain activation; wholeproteome and N-terminal peptide fractions were analysed by liquid chromatography and tandem mass spectrometry (LC-MS/MS), and spatial distributions were visualised by immunofluorescence confocal microscopy. Quantitative N-terminomics and proteomics revealed 69 calpain-1 substrates, 41 calpain-2 substrates, with 23 shared cleavage substrates, representing proteins implicated in signalling, cytoskeletal and metabolic proteins previously unlinked to calpain biology. Visualisation of calpain distribution within colon cancer cells by immunofluorescence microscopy identified spatial differences between calpain-1 and calpain-2. Our results demonstrate the capacity for our techniques to be applied to studying protease distribution and reveal novel unique characteristics of calpain-1 and -2. These insights refine the longstanding view of calpains as interchangeable effectors, demonstrating instead that each isoform occupies a distinct biochemical and spatial niche in colorectal cancer cells. The work establishes a curated substrate catalogue, iv identifies cleavage-site motifs for future prediction algorithms, and lays experimental groundwork for isoform-selective therapeutic targeting
Scaling up Production of Pluripotent Stem Cells in Stirred Suspension Bioreactors for Regenerative Medicine
No full textThis thesis focused on overcoming engineering challenges of using stirred suspension bioreactors for optimized PSC expansion and production scale-up. This objective was achieved through a combination of computational modeling and biological testing. Computational fluid dynamic modeling of various scale horizontal-blade stirred suspension bioreactors and single-use vertical-wheel bioreactors mapped out a hydrodynamic comparison that could be used for scale-up and scale-out predictions. Mouse embryonic stem cells were first cultured as aggregates in traditional horizontal-blade bioreactors to establish an understanding between hydrodynamic distributions, cell growth kinetics, aggregate sizes and distributions, and pluripotency maintenance. Bioprocess bottlenecks surrounding cryopreservation, inoculation density, and 3D serially passaging were addressed before beginning work with hiPSC stem cell cultures. hiPSC culture was optimized in vertical-wheel bioreactors, a scalable platform designed specifically for use with shear sensitive stem cell. Studies were completed to optimize inoculation methods, agitation rates, oxygen availability and nutrient availability. The vertical-wheel bioreactor was used as an effective tool in the design of single-cell inoculation methods and the first published protocol for in-vessel aggregate dissociation. Finally, results from these studies were compiled to better understand the relationships between the bioreactor hydrodynamic environments and PSC biological outputs. From here, effective scale-up correlation equations were derived allowing operators to define a working range of hydrodynamic variables at one scale and calculate corresponding agitation rates at other modeled scales. These equations were derived to maintain the CFD calculated variable of volume average energy dissipation rate. This variable was found to greatly impact cell quantity and quality through the hydrodynamic control of aggregate size and homogeneity. A suggested operating range of agitation rates was set and biologically validated for the successful culture and scale-up of iPSCs aggregates. Taken together, this thesis provides a set of tools and protocols for the robust expansion and scale-up of defined high-quality PSCs in stirred suspension bioreactors as a critical step in advancing cell therapy towards clinical cures in the field of regenerative medicine
Mesenchymal Progenitors in the Epidural Fat and Dura Mater Participate in Tissue Homeostasis and Wound Healing
No full textMesenchymal progenitor cells (MPCs) are adult cells capable of self-renewal and differentiation into cells that make up mesodermal tissues such as bone, cartilage, and fat. MPCs are believed to play a significant role in tissue maintenance and repair. MPCs are present in many adult connective tissues but are typically found in higher quantities in adipose tissues for yet unknown reasons. Recently, our research group identified MPC populations within epidural fat and the adjacent dura mater. Clinically, epidural fat is frequently considered a space-filling, biologically inert tissue; therefore, it is common practice for spine surgeons to discard it during surgical procedures. As the development and cellular origins of both epidural fat and the dura mater remain unclear, I hypothesized that epidural fat MPCs contribute to the maintenance of dural integrity throughout growth and post-injury. Using Paired related homeobox 1 (Prx1) and Hypermethylated in cancer 1 (Hic1) transgenic lineage tracing mice, the localization of epidural fat MPCs were identified during normal maturation and at skeletal maturity. This lineage tracing revealed an overlap between Prx1+ and Hic1+ populations, indicating a potential hierarchical relationship between the two MPC populations. When Prx1+/ Hic1+ MPCs were ablated, the expression of the dural marker α-SMA was lost in adjacent dura mater suggesting these cells are required for tissue homeostasis. Both MPC populations were observed to respond to dural injuries by homing to the lesion site. The process by which epidural fat MPCs maintain the dura mater through growth and after injury was accelerated in p21-/- mice (known for increased tissue regeneration/ cell proliferation). While MPCs have been identified and characterized in other adipose tissues, the role in epidural fat remained elusive. This study contributed to our knowledge of the role of epidural fat MPCs in vivo in aspects of growth, homeostasis, and repair of dural tissue. This thesis emphasizes the importance of revisiting the prevalent notion of epidural fat as biologically insignificant and the process of discarding it during surgery
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
- …
