The not-so-barren ranges

© Thesis Eleven Pty, Ltd., SAGE Publications. This is an impressionistic and informal essay written near the end of a novelist's Australia Research Council funded research project: 'Developing narratives from language and stories indigenous to the south coast of Western Australia', and informed by how that research project morphed into an emphasis on revitalization of Noongar language, and the attempt to restore connections between a particular Creation Story and landscape in an area regarded as 'massacre territory'. A sympathetic reader might think of the topic as 'The Wirlomin Noongar Language and Stories Project meets The Barren Ranges'

Hepatocyte Growth Factor (HGF) Inhibits Collagen I and IV Synthesis in Hepatic Stellate Cells by miRNA-29 Induction

BACKGROUND: In chronic liver disease, hepatic stellate cells (HSC) transdifferentiate into myofibroblasts, promoting extracellular matrix (ECM) synthesis and deposition. Stimulation of HSC by transforming growth factor-β (TGF-β) is a crucial event in liver fibrogenesis due to its impact on myofibroblastic transition and ECM induction. In contrast, hepatocyte growth factor (HGF), exerts antifibrotic activities. Recently, miR-29 has been reported to be involved in ECM synthesis. We therefore studied the influence of HGF and TGF-β on the miR-29 collagen axis in HSC. METHODOLOGY: HSC, isolated from rats, were characterized for HGF and Met receptor expression by Real-Time PCR and Western blotting during culture induced myofibroblastic transition. Then, the levels of TGF-β, HGF, collagen-I and -IV mRNA, in addition to miR-29a and miR-29b were determined after HGF and TGF-β stimulation of HSC or after experimental fibrosis induced by bile-duct obstruction in rats. The interaction of miR-29 with 3'-untranslated mRNA regions (UTR) was analyzed by reporter assays. The repressive effect of miR-29 on collagen synthesis was studied in HSC treated with miR-29-mimicks by Real-Time PCR and immunoblotting. PRINCIPAL FINDINGS: The 3'-UTR of the collagen-1 and -4 subtypes were identified to bind miR-29. Hence, miR-29a/b overexpression in HSC resulted in a marked reduction of collagen-I and -IV synthesis. Conversely, a decrease in miR-29 levels is observed during collagen accumulation upon experimental fibrosis, in vivo, and after TGF-β stimulation of HSC, in vitro. Finally, we show that during myofibroblastic transition and TGF-β exposure the HGF-receptor, Met, is upregulated in HSC. Thus, whereas TGF-β stimulation leads to a reduction in miR-29 expression and de-repression of collagen synthesis, stimulation with HGF was definitely associated with highly elevated miR-29 levels and markedly repressed collagen-I and -IV synthesis. CONCLUSIONS: Upregulation of miRNA-29 by HGF and downregulation by TGF-β take part in the anti- or profibrogenic response of HSC, respectively

Difficulty with daily activities involving the lower extremities in people with systemic sclerosis.

The purpose of this study was to examine the extent of lower extremity impairments in motion and strength in people with systemic sclerosis and the relationships of the impairments to limitations in activities of daily living primarily involving the lower extremities. Participants were 69 persons with SSc who received evaluations of lower extremity joint motion (Keitel function test), strength (timed-stands test), and basic mobility (timed up and go test) and completed a demographic questionnaire regarding symptoms in the lower extremities. Activity limitations were measured by the Rheumatoid and Arthritis Outcome Score (RAOS) which examines functional ability, pain, and quality of life. The participants had difficulty with items requiring external rotation of the hips and lower extremity strength. There were moderate correlations between the impairment measures of joint motion, strength, mobility, and activity limitations. Fair correlations were found between the skin scores and the RAOS sections except for pain. The results of this study show that lower extremity involvement is present in persons with SSc. The findings, regarding strength, mobility, and joint motion are related to the ability to perform everyday activities involving the lower extremities, suggest that these areas should be targeted for intervention in persons with SSc