Inducible resistance to maize streak virus

Maize streak virus (MSV), which causes maize streak disease (MSD), is the major viral pathogenic constraint on maize production in Africa. Type member of the Mastrevirus genus in the family Geminiviridae, MSV has a 2.7 kb, single-stranded circular DNA genome encoding a coat protein, movement protein, and the two replication-associated proteins Rep and RepA. While we have previously developed MSV-resistant transgenic maize lines constitutively expressing ‘‘dominant negative mutant’’ versions of the MSV Rep, the only transgenes we could use were those that caused no developmental defects during the regeneration of plants in tissue culture. A better transgene expression system would be an inducible one, where resistance-conferring transgenes are expressed only in MSV-infected cells. However, most known inducible transgene expression systems are hampered by background or ‘‘leaky’’ expression in the absence of the inducer. Here we describe an adaptation of the recently developed INPACT system to express MSV-derived resistance genes in cell culture. Split gene cassette constructs (SGCs) were developed containing three different transgenes in combination with three different promoter sequences. In each SGC, the transgene was split such that it would be translatable only in the presence of an infecting MSV’s replication associated protein. We used a quantitative real-time PCR assay to show that one of these SGCs (pSPLITrepIII-Rb-Ubi) inducibly inhibits MSV replication as efficiently as does a constitutively expressed transgene that has previously proven effective in protecting transgenic maize from MSV. In addition, in our cell-culture based assay pSPLITrepIII-Rb-Ubi inhibited replication of diverse MSV strains, and even, albeit to a lesser extent, of a different mastrevirus species. The application of this new technology to MSV resistance in maize could allow a better, more acceptable product.

Murine, but not human, ephrin-B2 can be efficiently cleaved by the serine protease kallikrein-4: Implications for xenograft models of human prostate cancer

Background Ephrin-B2 is the sole physiologically-relevant ligand of the receptor tyrosine kinase EphB4, which is over-expressed in many epithelial cancers, including 66% of prostate cancers, and contributes to cancer cell survival, invasion and migration. Crucially, however, the cancer-promoting EphB4 signalling pathways are independent of interaction with its ligand ephrin-B2, as activation of ligand-dependent signalling causes tumour suppression. Ephrin-B2, however, is often found on the surface of endothelial cells of the tumour vasculature, where it can regulate angiogenesis to support tumour growth. Proteolytic cleavage of endothelial cell ephrin-B2 has previously been suggested as one mechanism whereby the interaction between tumour cell-expressed EphB4 and endothelial cell ephrin-B2 is regulated to support both cancer promotion and angiogenesis. Methods An in silico approach was used to search accessible surfaces of 3D protein models for cleavage sites for the key prostate cancer serine protease, KLK4, and this identified murine ephrin-B2 as a potential KLK4 substrate. Mouse ephrin-B2 was then confirmed as a KLK4 substrate by in vitro incubation of recombinant mouse ephrin-B2 with active recombinant human KLK4. Cleavage products were visualised by SDS-PAGE, silver staining and Western blot and confirmed by N-terminal sequencing. Results At low molar ratios, KLK4 cleaved murine ephrin-B2 but other prostate-specific KLK family members (KLK2 and KLK3/PSA) were less efficient, suggesting cleavage was KLK4-selective. The primary KLK4 cleavage site in murine ephrin-B2 was verified and shown to correspond to one of the in silico predicted sites between extracellular domain residues arginine 178 and asparagine 179. Surprisingly, the highly homologous human ephrin-B2 was poorly cleaved by KLK4 at these low molar ratios, likely due to the 3 amino acid differences at this primary cleavage site. Conclusion These data suggest that in in vivo mouse xenograft models, endogenous mouse ephrin-B2, but not human tumour ephrin-B2, may be a downstream target of cancer cell secreted human KLK4. This is a critical consideration when interpreting data from murine explants of human EphB4+/KLK4+ cancer cells, such as prostate cancer cells, where differential effects may be seen in mouse models as opposed to human clinical situations.

Plain packaging for the Pacific Rim: The Trans-Pacific Partnership and tobacco control

Big Tobacco has been engaged in a dark, shadowy plot and conspiracy to hijack the Trans-Pacific Partnership Agreement (TPP) and undermine tobacco control measures – such as graphic health warnings and the plain packaging of tobacco products... In the context of this heavy lobbying by Big Tobacco and its proxies, this chapter provides an analysis of the debate over trade, tobacco, and the TPP. This discussion is necessarily focused on the negotiations of the free trade agreement – the shadowy conflicts before the finalisation of the text. This chapter contends that the trade negotiations threaten hard-won gains in public health – including international developments such as the WHO Framework Convention on Tobacco Control, and domestic measures, such as graphic health warnings and the plain packaging of tobacco products. It maintains that there is a need for regional trade agreements to respect the primacy of the WHO Framework Convention on Tobacco Control. There is a need both to provide for an open and transparent process regarding such trade negotiations, as well as a due and proper respect for public health in terms of substantive obligations. Part I focuses on the debate over the intellectual property chapter of the TPP, within the broader context of domestic litigation against Australia’s plain tobacco packaging regime and associated WTO disputes. Part II examines the investment chapter of the TPP, taking account of ongoing investment disputes concerning tobacco control and the declared approaches of Australia and New Zealand to investor-state dispute settlement. Part III looks at the discussion as to whether there should be specific text on tobacco control in the TPP, and, if so, what should be its nature and content. This chapter concludes that the plain packaging of tobacco products – and other best practices in tobacco control – should be adopted by members of the Pacific Rim.

The High Court of Australia and the Marlboro Man: The Battle Over the Plain Packaging of Tobacco Products

In 2012, the High Court of Australia handed down a landmark decision on the plain packaging of tobacco products. This chapter considers the historic ruling in the case of JT International SA v Commonwealth; British American Tobacco Australasia Ltd v Commonwealth. This chapter explores several themes in the decision. First, it highlights the historical work by the High Court of Australia on the role of health regulation, the use of health warnings, and tobacco control. Second, the chapter considers the High Court of Australia's view that intellectual property law promotes the public interest.Third, it explores the High Court of Australia’s analysis of the constitutional law on acquisition of property on just terms. Finally, this chapter contends that the High Court of Australia's ruling on plain packaging of tobacco products will spark an 'Olive Revolution' — and will encourage superior courts and policy-makers to follow suit.

The case for the plain packaging of tobacco products

AIMS: The Framework Convention on Tobacco Control (FCTC) requires nations that have ratified the convention to ban all tobacco advertising and promotion. In the face of these restrictions, tobacco packaging has become the key promotional vehicle for the tobacco industry to interest smokers and potential smokers in tobacco products. This paper reviews available research into the probable impact of mandatory plain packaging and internal tobacco industry statements about the importance of packs as promotional vehicles. It critiques legal objections raised by the industry about plain packaging violating laws and international trade agreements. METHODS: Searches for available evidence were conducted within the internal tobacco industry documents through the online document archives; tobacco industry trade publications; research literature through the Medline and Business Source Premier databases; and grey literature including government documents, research reports and non-governmental organization papers via the Google internet search engine. RESULTS: Plain packaging of all tobacco products would remove a key remaining means for the industry to promote its products to billions of the world's smokers and future smokers. Governments have required large surface areas of tobacco packs to be used exclusively for health warnings without legal impediment or need to compensate tobacco companies. CONCLUSIONS: Requiring plain packaging is consistent with the intention to ban all tobacco promotions. There is no impediment in the FCTC to interpreting tobacco advertising and promotion to include tobacco packs.

Price and trade: World no tobacco day 2015

This special issue of Tobacco Control for World No Tobacco Day is focused on the theme of Price and Trade.

The race to patent the SARS virus: The TRIPS agreement and access to essential medicines

This article considers the race to sequence the Severe Acute Respiratory Syndrome virus ('the SARS virus') in light of the debate over patent law and access to essential medicines. Part II evaluates the claims of public research institutions in Canada, the United States, and Hong Kong, and commercial companies, to patent rights in respect of the SARS virus. It highlights the dilemma of ’defensive patenting' - the tension between securing private patent rights and facilitating public disclosure of information and research. Part III considers the race to patent the SARS virus in light of wider policy debates over gene patents. It examines the application of such patent criteria as novelty, inventive step, utility, and secret use. It contends that there is a need to reform the patent system to accommodate the global nature of scientific inquiry, the unique nature of genetics, and the pace of technological change. Part IV examines the role played by the World Trade Organization and the World Health Organization in dealing with patent law and access to essential medicines. The article contends that there is a need to ensure that the patent system is sufficiently flexible and adaptable to accommodate international research efforts on infectious diseases.

Tobacco's mad men threaten public health

Non-communicable diseases – Matthew Rimmer examines plain packaging as a way to curb tobacco use. Smoking is one of the biggest causes of non-communicable diseases.

Big tobacco's box fetish: Plain packaging at the High Court

Tobacco, says the World Health Organisation (WHO), is “the only legal consumer product that kills when used exactly as intended by the manufacturer.”

No future? End the Future Fund's affair with Big Tobacco

Australia has shown outstanding leadership on tobacco control - but it could do more. The next step is surely for the Future Fund to quit its addiction to tobacco investments.