170,508 research outputs found
Cartilage development and degeneration:a Wnt Wnt situation
Full text linkMatrix Extracellular Phosphoglycoprotein (MEPE) is a member of a family of
proteins called small integrin-binding ligand, N-linked glycoproteins (SIBLINGs)
which play key roles in biomineralisation. Altered MEPE expression is associated
with several phosphate and bone-mineral metabolic disorders such as oncogenic
osteomalacia and hypophosphatemic rickets. Despite this, it remains undetermined
what impact MEPE has on the growth plate; the cartilage anlagen from which
endochondral ossification, the process responsible for linear bone growth, occurs.
The work of this thesis has characterised the ATDC5 cell line and the metatarsal
organ culture as useful in vitro models of endochondral ossification. These will
prove vital in the pursuit of underpinning the molecular mechanisms involved in
endochondral bone growth. These models form the basis of the further studies in
this thesis examining the role of MEPE within this highly orchestrated process.
Before such role can be defined, this thesis details the spatial and temporal
localisation patterns of MEPE in 10-day- and 4-week-old murine growth plates.
More specifically, MEPE protein and mRNA were preferentially expressed by the
hypertrophic chondrocytes as shown by immunohistochemistry and in situ
hybridisation respectively. Microdissection of the murine growth plate confirmed
this. Localisation of the cleavage product of MEPE, a 2.2kDa acidic serine- and
aspirate-rich motif (ASARM) peptide, followed a similar pattern of expression.
The localisation of MEPE to sites of mineralisation serves to strengthen its potential
role in chondrocyte matrix mineralisation. This thesis identified this role in both
mineralising ATDC5 cells and the metatarsal organ culture. The ASARM peptide
was found to be the functional component of MEPE and this function was
dependent upon its post-translational phosphorylation. Phosphorylated (p)ASARM
peptides significantly inhibited chondrocyte matrix mineralisation without altering
the proliferation or differentiation of the chondrocyte cells, or their ability to
produce an extracellular matrix. mRNA analysis by qPCR indicted a feedback
system by which the pASARM peptide functions to allow the release of further
ASARM peptides. Moreover, the pASARM peptide inhibited mRNA expression of
markers of vascular angiogenesis highlighting a novel mechanism by which they
may inhibit chondrocyte matrix mineralisation.
This thesis also determines the regulatory cross-talk between the chondrocytes of
the murine growth plate, with the most abundant bone cell type, the osteocyte. This
cross-talk inhibits chondrocyte matrix mineralisation and is attributed to sclerostin,
an osteocyte-specific secretory protein. Furthermore, it is shown that sclerostin acts
through the MEPE-ASARM axis to regulate chondrocyte matrix mineralisation and
thus endochondral ossification.
The work described herein has characterised and validated in vitro models of
growth plate chondrocyte matrix mineralisation and has used these to identify the
role of MEPE within chondrocyte matrix mineralisation
Examining graduate training in written language (Summy & Farquharson, 2024)
No full textPurpose: This study had two aims. Aim 1 was to query both communication science and disorders (CSD) faculty and school-based speech-language pathologists (SLPs) regarding how written language is/was covered in their graduate programs. Aim 2 was to query school-based SLPs about their written language service provision.Method: CSD faculty (n = 143) and school-based SLPs (n = 610) completed an online survey examining (a) if and how written language was addressed in their graduate program, (b) what content related to written language was covered in graduate school, and (c) provision of written language services in schools (SLPs only).Results: There was a discrepancy in reports of training provision. Faculty reported providing more training than SLPs reported receiving. However, SLPs with fewer years of experience reported slightly higher levels of training compared to those with more years of experience. Additionally, there was variability among SLPs in how often they targeted written language in therapy. Finally, receipt of training in written language was a significant predictor of provision of written language services, as reported by SLPs.Conclusions: SLPs play a key role on literacy teams in schools, but many SLPs did not receive adequate training in written language. In order to ensure SLPs are trained to work with children with reading difficulties, graduate programs should ensure that written language is part of the clinical and academic curricula.Supplemental Material S1. Demographics.Summy, R., & Farquharson, K. (2024). Examining graduate training in written language and the impact on speech-language pathologists’ practice: perspectives from faculty and clinicians. American Journal of Speech-Language Pathology, 33(1), 189–202. https://doi.org/10.1044/2023_AJSLP-22-00327</p
Tenascin-C: a marker and driver of inflammation
Full text linkTenascin-C, the founding member of the matricellular tenascin family, is a large multifunctional hexameric extracellular matrix (ECM) glycoprotein. It is abundantly expressed in the developing embryo but its expression becomes tightly regulated in the adult. However, during inflammatory responses tenascin-C becomes highly upregulated where it acts to create a local pro-inflammatory ‘niche’. In this proinflammatory role tenascin-C has been implicated in the pathogenesis of a variety of chronic inflammatory diseases including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), both of which are characterised by upregulated tenascin-C locally and systemically.
The work of this thesis has looked to expand upon this earlier work, identifying tenascin-C as a key driver as well as marker of inflammation, and further probe its mechanistic role in the inflammatory response and utility as a biomarker of inflammatory disease.
To answer the first question regarding tenascin-C’s role in pathological inflammation a murine Dextran Sulphate Sodium (DSS) model of chemically induced colitis was utilised. This thesis details the spatial and temporal expression of tenascin-C in the colon under basal conditions as well as the inflammatory state of the DSS model. Tenascin-C demonstrated a marked upregulation within the inflamed mucosa coinciding with the upregulation of other pro-inflammatory mediators and immune cell infiltration.
Following this descriptive characterisation, subsequent studies probed the mechanistic relevance of this upregulation utilising the same model in combination with a tenascin-C knockout mouse. These studies showed a protective effect of tenascin-C’s genetic ablation on the severity of the colitis induced. This included reductions in gross pathology as well as histopathology including lower inflammation and tissue damage observed during the acute stage.
Finally, with this mechanistic link clearly established between tenascin-C and the inflammatory diseased state this thesis aimed to explore tenascin-Cs utility as a disease marker, with a focus on RA. To this end, a number of novel immunoassays were established and validated for the measurement of tenascin-C and autoantibodies against in human serum samples. Screening of serum samples with these assays showed significantly higher levels of tenascin-C or autoantibodies against it in the serum of RA patients compared to healthy controls. These changes were not entirely RA specific however with a number of other inflammatory diseases tested also showing higher serum tenascin-C levels.
The work described herein has utilised the DSS colitis model in combination with tenascin-C knockout mice to demonstrate the role of tenascin-C as a driver of inflammatory disease and has further shown translational relevance as a disease marker in human patients
HVAC Occupancy Sensors
No full textJames Farquharson, Buyer/Inventory Manager, Residential & Auxiliary Services ($10,280.00 )
Georgia Southern’s Housing department converted four of the housing complexes’ clubhouses from standard A/C units to occupancy sensor-operated A/C units. We had 24 units installed in a building at Freedom’s Landing for testing. These sensor-activated air conditioning units lower or raise the temperature based on whether the room is occupied or not. With the installation of these units, we were able to reduce energy consumption as well as unit turnover and maintenance as they will be used less frequently and harshly
FIGURE 2 in Gnathia marleyi sp. nov. (Crustacea, Isopoda, Gnathiidae) from the Eastern Caribbean
No full textFIGURE 2. Cephalosome appendages of male Gnathia marleyi sp. nov. Male holotype, 3.3 mm (Crustacea Cat. No. 20223). A, Pylopod. B, Maxilliped. C, Articles 2 and 3 of pylopod. Scale-bars: A, B, 200 μm; C, 100µm.Published as part of Farquharson, Charon, Smit, Nico J. & Sikkel, Paul C., 2012, Gnathia marleyi sp. nov. (Crustacea, Isopoda, Gnathiidae) from the Eastern Caribbean, pp. 47-61 in Zootaxa 3381 on page 50, DOI: 10.5281/zenodo.21283
The initiation and progression of late-life romantic relationships
Full text linkThis research explores the initiation and progression of new late-life romantic relationships among older Australians (60 years plus). Our research found that older adult romantic relationships were meaningful, important and sexually intimate. However, few led to cohabitation or marriage, with these older adults preferring to date or to maintain separate households (living-apart- together, LAT). In line with Giddens’ ideal of ‘pure’ relationships, our research indicates that older adults are looking for egalitarian relationships based on emotional and sexual equality, albeit not necessarily based on cohabitation or monogamy
The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438
Full text linkLong-term use of glucocorticoids (GC) can cause growth retardation in children due to their actions on growth plate chondrocytes. AL-438, a non-steroidal anti-inflammatory agent that acts through the glucocorticoid receptor (GR) retains full anti-inflammatory efficacy but has reduced negative effects on osteoblasts compared to those elicited by prednisolone (Pred) or dexamethasone (Dex). We have used the murine chondrogenic ATDC5 cell line to compare the effects of AL-438 with those of Dex and Pred on chondrocyte dynamics. Dex and Pred caused a reduction in cell proliferation and proteoglycan synthesis, whereas exposure to AL-438 had no effect. LPS-induced IL-6 production in ATDC5 cells was reduced by Dex or AL-438, showing that AL-438 has similar anti-inflammatory efficacy to Dex in these cells. Fetal mouse metatarsals grown in the presence of Dex were shorter than control bones whereas AL-438 treated metatarsals paralleled control bone growth. These results indicate that the adverse effects Dex or Pred have on chondrocyte proliferation and bone growth were attenuated following AL-438 exposure, suggesting that AL-438 has a reduced side effect profile on chondrocytes compared to other GCs. This could prove important in the search for new anti-inflammatory treatments for children
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
Acute opioid administration induces hypothalamic-pituitary-adrenal activation and is mediated by genetic variation in interleukin (Il)1B
No full textAbstract not availableStephanie G. Kershaw, Chris B. Della Vedova, Irina Majumder, Michael B.Ward, Aaron L. Farquharson, Paul A.Williamson, Jason M.Whit
Linguistic ideologies and the historical development of language use patterns in Jamaican music
No full textFarquharson J. Linguistic ideologies and the historical development of language use patterns in Jamaican music. LANGUAGE & COMMUNICATION. 2017;52(SI):7-18.This paper presents Jamaica as a case study of the intersections between language practice, language ideologies, and music, using a historically grounded descriptive approach spanning a period of more than three and a half centuries. It describes secular and religious Jamaican music(s) and ideologies connected to them through different periods of the country's history characterised by different social and socio-political configurations (e.g., slavery, colonial rule, Independence). These systems and the emergent socialities to which they gave rise influenced the creation of new musical genres and determined to varying extents how linguistic codes were distributed by genre, and in the lyrics themselves. (C) 2016 Elsevier Ltd. All rights reserved
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