Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A

We show that in melanoma cells oncogenic BRAF, acting through MEK and the transcription factor BRN2, downregulates the cGMP-specific phosphodiesterase PDE5A. Although PDE5A downregulation causes a small decrease in proliferation, its major impact is to stimulate a dramatic increase in melanoma cell invasion. This is because PDE5A downregulation leads to an increase in cGMP, which induces an increase in cytosolic Ca2+, stimulating increased contractility and inducing invasion. PDE5A downregulation also this leads to an increase in short-term and long-term colonization of the lungs by melanoma cells. We do not observe this pathway in NRAS mutant melanoma or BRAF mutant colorectal cells. Thus, we show that in melanoma cells oncogenic BRAF induces invasion through downregulation of PDE5A.

Wilds of the Canadian Rockies

A travel article about touring in the Rockies, Alberta. MORAINE Lake, held up by a crown of mountains near the small town of Lake Louise, is opal blue. You'd need a precious stone to cut the surface. And even on a hot morning in August, there are plenty around: diamonds of snow decorate the mountain tops and, in their reflections, slice the lake with white triangles. We are at the start of a track that climbs from the lake to Mt Temple, the tallest mountain in the area and two or three hours' walk away. When the track zigzags back, we glimpse the lake through gaps in the conifer forest...

Moved by spirit of Canadian nature

A travel article about a visit to Klemtu and the Great Bear Rainforest, British Columbia. A LOW-TIDE mark of rocks coated in orange seaweed borders the islands of the Great Bear Rainforest. Our seaplane stays low under the clouds. As we approach the village of Klemtu, turning into Finlayson Channel, the trees beneath us thicken against the shoreline like a concert crowd being pushed from behind. There's no gap between the dark, still sea and the front row of soaring conifers, seemingly no entry point into one of the last great wilderness areas.

A comparison of Australian and Canadian informatics competencies for undergraduate nurses

Health information technologies (HIT) have changed healthcare delivery. Yet, there are few opportunities for student nurses in their undergraduate studies to develop nursing informatics competencies. More importantly, many countries around the world have not fully specified nursing informatics competencies that will be expected of student nurses prior to their graduation from undergraduate nursing programs. In this paper the authors compare and contrast the undergraduate nursing informatics competencies that were developed by two countries: Australia and Canada. They also identify some of the challenges and future research directions in the area.

Report: The Canadian Best Practices Educational Toolkits: Translating evidence-based stroke recommendations into practical implementation resources

The Canadian Best Practice Recommendations for Stroke Care are intended to reduce variations in stroke care and facilitate closure of the gap between evidence and practice (Lindsay et al., 2010). The publication of best practice recommendations is only the beginning of this process. The guidelines themselves are not sufficient to change practice and increase consistency in care. Therefore, a key objective of the Canadian Stroke Network (CSN) Best Practices Working Group (BPWG) is to encourage and facilitate ongoing professional development and training for health care professionals providing stroke care. This is addressed through a multi-factorial approach to the creation and dissemination of inter-professional implementation tools and resources. The resources developed by CSN span pre-professional education, ongoing professional development, patient education and may be used to inform systems change. With a focus on knowledge translation, several inter-professional point-of-care tools have been developed by the CSN in collaboration with numerous professional organizations and expert volunteers. These resources are used to facilitate awareness, understanding and applications of evidence-based care across stroke care settings. Similar resources are also developed specifically for stroke patients, their families and informal caregivers, and the general public. With each update of the Canadian Best Practice Recommendations for Stroke Care, the BPWG and topic-specific writing groups propose priority areas for ongoing resource development. In 2010, two of these major educational initiatives were undertaken and recently completed—one to support continuing education for health care professionals regarding secondary stroke prevention and the other to educate families, informal caregivers and the public about pediatric stroke. This paper presents an overview of these two resources, and we encourage health care professionals to integrate these into their personal learning plans and tool kits for patients.

Canadian rhapsody: Copyright law and research libraries

This article considers the ground-breaking Supreme Court of Canada decision in The Law Society of Upper Canada v CCH Canadian Limited. The matter involved legal publishers bringing an action for copyright infringement against the Law Society of Upper Canada for operating a photocopy and custom copy service at the Great Library of Osgoode Hall. The Supreme Court of Canada decision laid down important precedents in relation to originality, authorisation, and the defence of fair dealing. The ruling has been hailed as ’one of the strongest pro-user rights decisions from any high court in the world, showing what it means to do more than pay mere lip service to balance in copyright'. This decision will have important implications for the regulation of new technologies. The approach has been applied in two decisions dealing copyright law and the Internet - the Canadian Federal Court case of BMG Canada v John Doe, and the Supreme Court of Canada ’Tariff 22' case. The Supreme Court of Canada decision in The Law Society of Upper Canada v CCH Canadian Limited provides an impetus to reconsider the judicial interpretation of user rights in Australian jurisprudence.

Remixing Canadian copyright law: A review essay on'An Emerging Intellectual Property Paradigm','Canadian Copyright: A Citizen's Guide'; and'RiP!: A Remix Manifesto', Prometheus, Vol. 27 (3), p. 297-305

In her album, Hymns of the 49th Parallel, the chanteuse K.D. Lang pays tribute to a series of great Canadian songwriters—such as Neil Young, Leonard Cohen, Joni Mitchell and Jane Siberry. In a similar spirit of celebration, this review essay pays homage to a number of recent texts and films dealing with Canadian intellectual property. First, it considers Ysolde Gendreau’s collection, An Emerging Intellectual Property Paradigm: Perspectives from Canada. Second, this essay looks at Laura Murray and Samuel Trosow’s manual, Canadian Copyright: A Citizen’s Guide. Finally, this review evaluates Brett Gaylor’s documentary, RiP! A Remix Manifesto. The three works share certain affinities—a spirit of scepticism about the legitimacy and the efficacy of existing networks of law, policy and bureaucracy; a populist interest in the impact of intellectual property on the everyday lives of citizens, creators and consumers; a passion for human rights; and a melioristic desire for sensible law reform of copyright law and related regimes of intellectual property.

Pathogens penetrating the central nervous system: Infection pathways and the cellular and molecular mechanisms of invasion

The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Following Stroke practice guidelines, update 2015

Every year, approximately 62 000 people with stroke and transient ischemic attack are treated in Canadian hospitals, and the evidence suggests one-third or more will experience vascular-cognitive impairment, and/or intractable fatigue, either alone or in combination. The 2015 update of the Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Module guideline is a comprehensive summary of current evidence-based recommendations for clinicians in a range of settings, who provide care to patients following stroke. The three consequences of stroke that are the focus of the this guideline (poststroke depression, vascular cognitive impairment, and fatigue) have high incidence rates and significant impact on the lives of people who have had a stroke, impede recovery, and result in worse long-term outcomes. Significant practice variations and gaps in the research evidence have been reported for initial screening and in-depth assessment of stroke patients for these conditions. Also of concern, an increased number of family members and informal caregivers may also experience depressive symptoms in the poststroke recovery phase which further impact patient recovery. These factors emphasize the need for a system of care that ensures screening occurs as a standard and consistent component of clinical practice across settings as stroke patients transition from acute care to active rehabilitation and reintegration into their community. Additionally, building system capacity to ensure access to appropriate specialists for treatment and ongoing management of stroke survivors with these conditions is another great challenge.

Targeting neuropilin-1 to inhibit prostate cancer invasion and metastasis

Recent reports provide evidence that the epithelial-to-mesenchymal transition (EMT) plays a key role in prostate cancer (PCa) metastasis and therapy resistance. We have recently identified the cell surface receptor, Neuropilin-1 (NRP1) to be increased during epithelial-mesenchymal transition (EMT) and this study aims to determine whether the inhibition of NRP1 will be a feasible therapeutic strategy for blocking PCa metastasis and therapy resistance.