Namoi : Talking fish - making connections with the rivers of the Murray-Darling Basin

The Namoi River winds its way through 42 000 square kilometres of blacksoil plain in the north east of New South Wales. Fed by the rivers of the western slopes of the Great Dividing Range, it contributes about one quarter of the Darling River’s flow. The river, its floodplain, wetlands, swamps and waterholes, are the traditional lands of the Gamilaraay* people. The Namoi is a very different river to the one the Gamilaraay people once knew and fished...

Bcl-2 genes and growth factors in the pathology of ischaemic acute renal failure

For the past decade, an attempt has been made by many research groups to define the roles of the growing number of Bcl-2 gene family proteins in the apoptotic process. The Bcl-2 family consists of pro-apoptotic (or cell death) and anti-apoptotic (or cell survival) genes and it is the balance in expression between these gene lineages that may determine the death or survival of a cell. The majority of studies have analysed the role/s of the Bcl-2 genes in cancer development. Equally important is their role in normal tissue development, homeostasis and non-cancer disease states. Bcl-2 is crucial for normal development in the kidney, with a deficiency in Bcl-2 producing such malformation that renal failure and death result. As a corollary, its role in renal disease states in the adult has been sought. Ischaemia is one of the most common causes of both acute and chronic renal failure. The section of the kidney that is most susceptible to ischaemic damage is the outer zone of the outer medulla. Within this zone the proximal tubules are most sensitive and often die by necrosis or desquamate. In the distal nephron, apoptosis is the more common form of cell death. Recent results from our laboratory have indicated that ischaemia-induced acute renal failure is associated with up-regulation of two anti-apoptotic Bcl-2 proteins (Bcl-2 and Bcl-XL) in the damaged distal tubule and occasional up-regulation of Bax in the proximal tubule. The distal tubule is a known reservoir for several growth factors important to renal growth and repair, such as insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF). One of the likely possibilities for the anti-cell death action of the Bcl-2 genes is that the protected distal cells may be able to produce growth factors that have a further reparative or protective role via an autocrine mechanism in the distal segment and a paracrine mechanism in the proximal cells. Both EGF and IGF-1 are also up-regulated in the surviving distal tubules and are detected in the surviving proximal tubules, where these growth factors are not usually synthesized. As a result, we have been using in vitro methods to test: (i) the relative sensitivities of renal distal and proximal epithelial cell populations to injury caused by mechanisms known to act in ischaemia-reperfusion; (ii) whether a Bcl-2 anti-apoptotic mechanism acts in these cells; and (iii) whether an autocrine and/or paracrine growth factor mechanism is initiated. The following review discusses the background to these studies as well as some of our preliminary results.

Interleukin-1β stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-β-dependent mechanism

One of the hallmarks of progressive renal disease is the development of tubulointerstitial fibrosis. This is frequently preceded by macrophage infiltration, raising the possibility that macrophages relay fibrogenic signals to resident tubulointerstitial cells. The aim of this study was to investigate the potentially fibrogenic role of interleukin-1beta (IL-1beta), a macrophage-derived inflammatory cytokine, on cortical fibroblasts (CFs). Primary cultures of human renal CFs were established and incubated for 24 hours in the presence or absence of IL-1beta. We found that IL-1beta significantly stimulated DNA synthesis (356.7% +/- 39% of control, P <.003), fibronectin secretion (261.8 +/- 11% of control, P <.005), collagen type 1 production, (release of procollagen type 1 C-terminal-peptide, 152.4% +/- 26% of control, P <.005), transforming growth factor-beta (TGF-beta) secretion (211% +/- 37% of control, P <.01), and nitric oxide (NO) production (342.8% +/- 69% of control, P <.002). TGF-beta (1 ng/mL) and the phorbol ester phorbol 12-myristate 13-acetate (PMA, 25 nmol/L) produced fibrogenic effects similar to those of IL-1beta. Neither a NO synthase inhibitor (N(G)-methyl-l-arginine, 1 mmol/L) nor a protein kinase C (PKC) inhibitor (bis-indolylmaleimide 1, 1 micromol/L) altered the enhanced level of fibronectin secretion or DNA synthesis seen in response to IL-1beta treatment. However, addition of a TGF-beta-neutralizing antibody significantly reduced IL-1beta-induced fibronectin secretion (IL-1beta + IgG, 262% +/- 72% vs IL-1beta + alphaTGF-beta 156% +/- 14%, P <.02), collagen type 1 production (IL-1beta + IgG, 176% +/- 28% vs IL-1beta + alphaTGF-beta, 120% +/- 14%, P <.005) and abrogated IL-1beta-induced DNA synthesis (245% +/- 49% vs 105% +/- 21%, P <.005). IL-1beta significantly stimulated CF DNA synthesis and production of fibronectin, collagen type 1, TGFbeta, and NO. The fibrogenic and proliferative action of IL-1beta on CF appears not to involve activation of PKC or production of NO but is at least partly TGFbeta-dependent.

Katarapko : Talking fish - making connections with the rivers of the Murray-Darling Basin

Once known as Crabb’s Creek, Katarapko Creek is a small anabranch of the Murray River, located between the towns of Berri and Loxton in the Riverland region of South Australia. Its 9 000 hectare grey clay floodplain is covered with blackbox, saltbush and lignum. The creek’s horseshoe lagoons, marshes and islands are the traditional lands of the Meru peoples. They fished the creek and surrounding waterways and hunted the wetlands. The ebb and flow of water guided their travels and featured in their stories. The Meru have seen their land and the river change...

Goulburn : Talking fish - making connections with the rivers of the Murray-Darling Basin

The Goulburn River’s cold, clear waters rush westward down from the steep hills and mountains of the Great Dividing Range toward Seymour. The river then turns northward and meanders through hills and plains until the river meets the Murray upstream of Echuca. These are the traditional lands of the Taungurung, Bangerang and Yorta Yorta peoples. However, the Goulburn River today is not the river the Taungurung, Bangerang and Yorta Yorta once knew and fished...

Upper Murrumbidgee : Talking fish - making connections with the rivers of the Murray-Darling Basin

The Upper Murrumbidgee cuts its way through the Snowy Mountains in south‐eastern New South Wales, snaking its way south, then turning north before dropping into the lowland and heading west to join the Murray downstream of Swan Hill. The Upper ‘Bidgee floodplain is only a couple of hundred metres wide, a stark contrast to the kilometres‐wide floodplains in other parts of the Murray‐ Darling Basin. When the floods come, they come up quickly and roar through the narrow valleys. These are the traditional lands of the Ngunnawal and Ngarigo peoples. They fished the river and surrounding waterways and hunted the wetlands. The seasonal rise and fall of the water guided their travels and featured in their stories. The Ngunnawal and Ngarigo people have seen their land and the river change...

Murray : Talking fish - making connections with the rivers of the Murray-Darling Basin

The Murray River is the boundary between NSW and Victoria. The river both defines boundaries and unites them with the waters that sustain townships, irrigation and the floodplain forests, including the 70 000ha of the iconic Barmah and Millewa Forest. The river and its floodplain are the traditional lands of the Yorta Yorta and Bangerang people. The Murray is a very different river to the one the Yorta Yorta and Bangerang peoples once knew and fished...

Darling and the Great Anabranch : Talking fish - making connections with the rivers of the Murray-Darling Basin

The Lower Darling River and Great Darling Anabranch are located in south west New South Wales. Muddy waters meander over the grey soil floodplains past red dunes, spiky saltbush and gnarled red gums. These are the traditional lands of the Paakintji people. But the land and the river are no longer what the Paakintji once knew and fished...

Upper Darling: Brewarrina to Bourke : Talking fish - making connections with the rivers of the Murray-Darling Basin

To say ‘Back o’ Bourke’ means ‘miles from anywhere’ to most Australians, however the Barwon and Darling Rivers that pass by the townships of Brewarrina and Bourke, respectively, are at the heart of the Murray‐Darling Basin. These are the traditional lands of the Ngiyampaa, Murawari and Yuwalaraay peoples (refer Aboriginal language groups in the Bringing back the fish section at the back of this booklet). They fished the river and surrounding waterways and hunted the wetlands. The Ngiyampaa, Murawari and Yuwalaraay people have seen their land and the rivers change...

Ovens : Talking fish - making connections with the rivers of the Murray-Darling Basin

The Ovens River rises in the Victorian Alps where it is linked to significant freshwater meadows and marshes. It flows past Harrietville, Bright, Myrtleford and Wangaratta where it is joined by the King River on its way to meet the Murray near the top of Lake Mulwala. These the traditional lands of the Bangerang people and their neighbours the Taungurung and Yorta Yorta peoples. They have fished the river and surrounding waterways and hunted the wetlands. The ebb and flow of water guided their travels and featured in their stories. The Bangerang, Taungurung and Yorta Yorta have seen their land and the river change...

The Coorong and Lower Lakes : Talking fish - making connections with the rivers of the Murray-Darling Basin

After gathering water from 23 river valleys, the Murray empties into Lakes Alexandrina and Albert before making its way to the Coorong and out the Murray Mouth to Encounter Bay in South Australia. The entire Murray‐Darling Basin is upstream. Everything that happens there affects what goes on here...

Estrogen receptor β activation impairs mitochondrial oxidative metabolism and affects malignant mesothelioma cell growth in vitro and in vivo

Estrogen receptor (ER)-β has been shown to possess a tumor suppressive effect, and is a potential target for cancer therapy. Using gene-expression meta-analysis of human malignant pleural mesothelioma, we identified an ESR2 (ERβ coding gene) signature. High ESR2 expression was strongly associated with low succinate dehydrogenase B (SDHB) (which encodes a mitochondrial respiratory chain complex II subunit) expression. We demonstrate that SDHB loss induced ESR2 expression, and that activated ERβ, by over-expression or by selective agonist stimulation, negatively affected oxidative phosphorylation compromising mitochondrial complex II and IV activity. This resulted in reduced mitochondrial ATP production, increased glycolysis dependence and impaired cell proliferation. The observed in vitro effects were phenocopied in vivo using a selective ERβ agonist in a mesothelioma mouse model. On the whole, our data highlight an unforeseen interaction between ERβ-mediated tumor suppression and energy metabolism that may be exploited to improve on the therapy for clinical management of malignant mesothelioma.

High-growth firms : characteristics, job contribution and method observations

Largely as a result of mass unemployment problems in many European countries, the dynamics of job creation has in recent years attracted increased interest on the part of academics as well as policy-makers. In connection to this, a large number of studies carried out in various countries have concluded that SMEs play a very large and/or growing role as job creators (Birch, 1979; Baldwin and Picot, 1995; Davidsson, 1995a; Davidsson, Lindmark and Olofsson, 1993; 1994; 1995; 1997a; 1997b; Fumagelli and Mussati, 1993; Kirchhoff and Phillips, 1988; Spilling, 1995; for further reference to studies carried out in a large number of countries see also Aiginger and Tichy, 1991; ENSR, 1994; Loveman and Sengenberger, 1991; OECD, 1987; Storey and Johnson, 1987). While most researchers agree on the importance of SMEs, there is some controversy as regards whether this is mainly a result of many small start-ups and incremental expansions, or if a small minority of high growth SMEs contribute the lion’s share of new employment. This is known as the ‘mice vs. gazelles’ or ‘flyers vs. trundlers’ debate. Storey strongly advocates the position that the small group of high growth SMEs are the ‘real’ job creators (Storey, 1994; Storey & Johnson, 1987), whereas, e.g., the Davidsson et al research in Sweden (cf. above) gives more support for the ‘mice’ hypothesis.

Identification of a long non-coding RNA gene, GHSROS (growth hormone secretagogue receptor opposite strand), which stimulates cell migration in non-small cell lung cancer cell lines

The molecular mechanisms involved in non‑small cell lung cancer tumourigenesis are largely unknown; however, recent studies have suggested that long non-coding RNAs (lncRNAs) are likely to play a role. In this study, we used public databases to identify an mRNA-like, candidate long non-coding RNA, GHSROS (GHSR opposite strand), transcribed from the antisense strand of the ghrelin receptor gene, growth hormone secretagogue receptor (GHSR). Quantitative real-time RT-PCR revealed higher expression of GHSROS in lung cancer tissue compared to adjacent, non-tumour lung tissue. In common with many long non-coding RNAs, GHSROS is 5' capped and 3' polyadenylated (mRNA-like), lacks an extensive open reading frame and harbours a transposable element. Engineered overexpression of GHSROS stimulated cell migration in the A549 and NCI-H1299 non-small cell lung cancer cell lines, but suppressed cell migration in the Beas-2B normal lung-derived bronchoepithelial cell line. This suggests that GHSROS function may be dependent on the oncogenic context. The identification of GHSROS, which is expressed in lung cancer and stimulates cell migration in lung cancer cell lines, contributes to the growing number of non-coding RNAs that play a role in the regulation of tumourigenesis and metastatic cancer progression.

Different in vitro activation methods for latent transforming growth factors (TGF)–β : considerable exogenous factors to promote higher mesenchymal-origin cell proliferation in a bioprocessing platform

Regenerative medicine includes two efficient techniques, namely tissue-engineering and cell-based therapy in order to repair tissue damage efficiently. Most importantly, huge numbers of autologous cells are required to deal these practices. Nevertheless, primary cells, from autologous tissue, grow very slowly while culturing in vitro; moreover, they lose their natural characteristics over prolonged culturing period. Transforming growth factors-beta (TGF-β) is a ubiquitous protein found biologically in its latent form, which prevents it from eliciting a response until conversion to its active form. In active form, TGF-β acts as a proliferative agent in many cell lines of mesenchymal origin in vitro. This article reviews on some of the important activation methods-physiochemical, enzyme-mediated, non-specific protein interaction mediated, and drug-induced- of TGF-β, which may be established as exogenous factors to be used in culturing medium to obtain extensive proliferation of primary cells.