54 research outputs found

    Flt-1 (VEGFR-1) coordinates discrete stages of blood vessel formation

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    In developing blood vessel networks, the overall level of vessel branching often correlates with angiogenic sprout initiations, but in some pathological situations, increased sprout initiations paradoxically lead to reduced vessel branching and impaired vascular function. We examine the hypothesis that defects in the discrete stages of angiogenesis can uniquely contribute to vessel branching outcomes

    Monitoring and dietary risk assessment of 81 pesticide residues in 11 local agricultural products from the 3 largest cities of Cameroon

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    This study monitored 81 pesticides residues in 160 samples of 11 dry agricultural products collected in the 3 largest cities of Cameroon, extracted using QuEChERS method and analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Residues of 58 (71.6%) compounds were found in the samples, the most distributed pesticides were Imazalil, Triadimenol and Pyrimethanil, and those with the highest average concentrations were Cymoxanil, Thiamethoxam and Thifensulfuron. Half of the positive pesticides were above their European Union maximum residue limits (MRLs) among which Carbaryl, Carbofuran, Malathion, Metalaxyl and Propoxur are pesticides banned in the country. All the 11 food items contained pesticides, the highest contamination rates (12.8%–5.0%) were found in white pepper, maize, Egusi seeds and groundnuts, while groundnuts, Egusi seeds, maize and soybeans showed the highest residue concentrations (1.46–1.37 mg/kg). Pesticide contamination rates were similar in the 3 sampling cities, but Bafoussam and Yaounde had more samples above the MRLs than Douala. Using the food consumption data for Cameroon from the recent Sub-Saharan Africa Total Diet Study, dietary exposure was calculated and potential health risk of Cameroonian consumers was evaluated. Hazard quotient of Carbofuran in groundnuts was 22% above the safe value, the remaining food items could be considered safe for individual pesticide residues, although Triazophos and Metribuzin in maize were of concern. Groundnuts (0.531) and maize (0.443) showed high hazard index, with 17 highly contributing compounds, but there is no reason to be concerned about cumulative exposure to residues from the food items. While the food items are in general safe to eat, to minimize the increasing human health risk of consumers and ensure approval of Cameroon export produces on international market, this study suggests that authorities must regulate the usage of agrochemicals, strengthen the controls for effective implementation of the pesticide bans and implement strong control of obsolete pesticide stocks in the country

    A Small Peptide Modeled after the NRAGE Repeat Domain Inhibits XIAP-TAB1-TAK1 Signaling for NF-κB Activation and Apoptosis in P19 Cells

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    In normal growth and development, apoptosis is necessary to shape the central nervous system and to eliminate excess neurons which are not required for innervation. In some diseases, however, apoptosis can be either overactive as in some neurodegenerative disorders or severely attenuated as in the spread of certain cancers. Bone morphogenetic proteins (BMPs) transmit signals for regulating cell growth, differentiation, and apoptosis. Responding to BMP receptors stimulated from BMP ligands, neurotrophin receptor-mediated MAGE homolog (NRAGE) binds and functions with the XIAP-TAK1-TAB1 complex to activate p38MAPK and induces apoptosis in cortical neural progenitors. NRAGE contains a unique repeat domain that is only found in human, mouse, and rat homologs that we theorize is pivotal in its BMP MAPK role. Previously, we showed that deletion of the repeat domain inhibits apoptosis, p38MAPK phosphorylation, and caspase-3 cleavage in P19 neural progenitor cells. We also showed that the XIAP-TAB1-TAK1 complex is dependent on NRAGE for IKK-α/β phosphorylation and NF-κB activation. XIAP is a major inhibitor of caspases, the main executioners of apoptosis. Although it has been shown previously that NRAGE binds to the RING domain of XIAP, it has not been determined which NRAGE domain binds to XIAP. Here, we used fluorescence resonance energy transfer (FRET) to determine that there is a strong likelihood of a direct interaction between NRAGE and XIAP occurring at NRAGE's unique repeat domain which we also attribute to be the domain responsible for downstream signaling of NF-κB and activating IKK subunits. From these results, we designed a small peptide modeled after the NRAGE repeat domain which we have determined inhibits NF-κB activation and apoptosis in P19 cells. These intriguing results illustrate that the paradigm of the NRAGE repeat domain may hold promising therapeutic strategies in developing pharmaceutical solutions for combating harmful diseases involving excessive downstream BMP signaling, including apoptosis

    Taxation of Sovereign Wealth Funds – A Suggested Approach

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    Sovereign wealth funds (SWFs) are used for large - scale offshore investment of government funds. In accordance with the sovereign immunity doctrine, a SWF is generally immune from the jurisdiction of another sovereign State – including tax laws. There has been little research on the application of tax to SWFs. Yet it is an issue of vital importance to Australia and to its international competitiveness and security. In 2009, the Australian Government announced its intention to codify its practices in dealing with SWFs and an Options Paper was released in 2011.This article reviews the practices adopted by Australia and selected countries in relation to taxing SWFs. It considers best practice principles, which Australia should adopt in developing policy for taxing these foreign investment vehicles. Australia’s current taxation regime and the model proposed in 2011, are discussed, and a model suggested for Australia

    Alternative Tax Dispute Resolution: Perspectives from ATO Officers

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    Tax disputes between taxpayers and tax administrators while common are costly to resolve, especially if they go beyond the tax administration for resolution. Attention by tax researchers and tax administrators has recently been paid to alternative dispute resolution (ADR) as an appropriate way for resolving tax disputes. The principle aim of this article is to examine ADR as a tool for resolving tax disputes and recent developments in alternative tax dispute resolution (ATDR) in Australia. The Australian Taxation Office (ATO) has adopted and implemented many initiatives that appear to improve its performance in ATDR which can in turn save time and costs for all stakeholders of the tax system, especially taxpayers. Our interview-based study suggests the commitment and direction of the ATO with respect to ATDR and raises the question whether these positive early steps can be maintained or even improved

    Little con

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    Performed on the last Friday of every month (December and January excluded) 2005 – at a variety of venues in Melbourne, including the Cecil Street Studio and the Dancehouse. Founders and regular participants: Shaun McLeod, Paul Romano, Ann-maree Ellis, Dianne Reid, Grace Walpole and Joseph Lehrer. National and international guest artists include: Rosalind Crisp (Australia & France), Andrew Morrish (Australia and France), Tony Osborne (Sydney), Jane McKernan (Sydney) and many other Melbourne based performers

    Antibody/ligand-target receptor internalization assay protocol using fresh human or murine tumor ex vivo samples

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    We describe an EGF ligand internalization assay using fresh patient tumor biopsies to determine how antigen targets will be trafficked before patients receive mAb treatment. This protocol facilitates a sensitive and reproducible indication as to mAbs surface retention times during treatment. EGF uptake protocols can also be used to analyze EGFR heterogeneity and localization of EGFR in both tumor and xenograft tissue. The technology can be adapted to analyze other receptors such as PD-L1 for which methods are provided. For complete details on the use and execution of this protocol, please refer to Joseph et\ua0al. (2019) and Chew et\ua0al. (2020)
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