Thorough assessment of DNA preservation from fossil bone and sediments excavated from a late Pleistocene–Holocene cave deposit on Kangaroo Island, South Australia

Fossils and sediments preserved in caves are an excellent source of information for investigating impacts of past environmental changes on biodiversity. Until recently studies have relied on morphology-based palaeontological approaches, but recent advances in molecular analytical methods offer excellent potential for extracting a greater array of biological information from these sites. This study presents a thorough assessment of DNA preservation from late Pleistocene–Holocene vertebrate fossils and sediments from Kelly Hill Cave Kangaroo Island, South Australia. Using a combination of extraction techniques and sequencing technologies, ancient DNA was characterised from over 70 bones and 20 sediment samples from 15 stratigraphic layers ranging in age from >20 ka to ∼6.8 ka. A combination of primers targeting marsupial and placental mammals, reptiles and two universal plant primers were used to reveal genetic biodiversity for comparison with the mainland and with the morphological fossil record for Kelly Hill Cave. We demonstrate that Kelly Hill Cave has excellent long-term DNA preservation, back to at least 20 ka. This contrasts with the majority of Australian cave sites thus far explored for ancient DNA preservation, and highlights the great promise Kangaroo Island caves hold for yielding the hitherto-elusive DNA of extinct Australian Pleistocene species.

Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways

Purpose Cancer cells have been shown to be more susceptible to Ran knockdown than normal cells. We now investigate whether Ran is a potential therapeutic target of cancers with frequently found mutations that lead to higher Ras/MEK/ERK [mitogen-activated protein/extracellular signal-regulated kinase (ERK; MEK)] and phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 activities. Experimental Design Apoptosis was measured by flow cytometry [propidium iodide (PI) and Annexin V staining] and MTT assay in cancer cells grown under different conditions after knockdown of Ran. The correlations between Ran expression and patient survival were examined in breast and lung cancers. Results Cancer cells with their PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways inhibited are less susceptible to Ran silencing-induced apoptosis. K-Ras-mutated, c-Met-amplified, and Pten-deleted cancer cells are also more susceptible to Ran silencing-induced apoptosis than their wild-type counterparts and this effect is reduced by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers. This association is dramatically enhanced in cancers with increased c-Met or osteopontin expression, or with oncogenic mutations of K-Ras or PIK3CA, all of which are mutations that potentially correlate with activation of the PI3K/Akt/mTORC1 and/or Ras/MEK/ERK pathways. Silencing Ran also results in dysregulation of nucleocytoplasmic transport of transcription factors and downregulation of Mcl-1 expression, at the transcriptional level, which are reversed by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Conclusion Ran is a potential therapeutic target for treatment of cancers with mutations/changes of expression in protooncogenes that lead to activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. ©2011 AACR.

Talking Fish : Making Connections with the Rivers of the Murray-Darling Basin

"The ongoing review of the NFS highlighted that engagement with recreational fishers and the Indigenous community, in particular, could be enhanced. This was the impetus for the Talking Fish project which acknowledged the important relationship people have with their local rivers and fish within the Murray-Darling Basin. Within these relationships a wealth of historical information about rivers and fish was held and it was recognised that this needed to be captured..."--publisher website.

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...

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...

Cholesterol regulates Syntaxin 6 trafficking at trans-Golgi network endosomal boundaries.

Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN). Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs). This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion.