title: A structural basis for the reduced toxicity of dinophysistoxin-2

authors: Huhn, Jason

subjects: dinophysistoxin

abstract: Okadaic acid (OA), dinophysistoxin-1 (DTX-1), and dinophysistoxin-2 (DTX-2) are algal toxins that can accumulate in shellfish and cause diarrhetic shellfish poisoning. Recent studies indicate that DTX-2 is about half as toxic and has about half the affinity for protein phosphatase 2A (PP2A) as OA. NMR structural studies showed that DTX-1 possessed an equatorial 35-methyl group but that DTX-2 had an axial 35-methyl group. Molecular modeling studies indicated that an axial 35-methyl could exhibit unfavorable interactions in the PP2A binding site, and this has been proposed as the reason for the reduced toxicity of DTX-2. Statistical analyses of published data indicate that the affinity of PP2A for DTX-1 is 1.6-fold higher, and for DTX-2 is 2-fold lower, than for OA. We obtained X-ray crystal structures of DTX-1 and DTX-2 bound to PP2A. The crystal structures independently confirm the C-35 stereochemistries determined in the earlier NMR study. The structure for the DTX-1 complex was virtually identical to that of the OA-PP2A complex, except for the presence of the equatorial 35-methyl on the ligand. The favorable placement of the equatorial 35-methyl group of DTX-1 against the aromatic π-bonds of His191 may account for the increased affinity of PP2A toward DTX-1. In contrast, the axial 35-methyl of DTX-2 caused the side chain of His191 to rotate 140° so that it pointed toward the solvent, thereby opening one end of the hydrophobic binding cage. This rearrangement to accommodate the unfavorable interaction from the axial 35-methyl of DTX-2 reduces the binding energy and appears to be responsible for the reduced affinity of PP2A for DTX-2. These results highlight the potential of molecular modeling studies for understanding the relative toxicity of analogues once the binding site at the molecular target has been properly characterized.

text: A structural basis for the reduced toxicity of dinophysistoxin-2 Okadaic acid (OA), dinophysistoxin-1 (DTX-1), and dinophysistoxin-2 (DTX-2) are algal toxins that can accumulate in shellfish and cause diarrhetic shellfish poisoning. Recent studies indicate that DTX-2 is about half as toxic and has about half the affinity for protein phosphatase 2A (PP2A) as OA. NMR structural studies showed that DTX-1 possessed an equatorial 35-methyl group but that DTX-2 had an axial 35-methyl group. Molecular modeling studies indicated that an axial 35-methyl could exhibit unfavorable interactions in the PP2A binding site, and this has been proposed as the reason for the reduced toxicity of DTX-2. Statistical analyses of published data indicate that the affinity of PP2A for DTX-1 is 1.6-fold higher, and for DTX-2 is 2-fold lower, than for OA. We obtained X-ray crystal structures of DTX-1 and DTX-2 bound to PP2A. The crystal structures independently confirm the C-35 stereochemistries determined in the earlier NMR study. The structure for the DTX-1 complex was virtually identical to that of the OA-PP2A complex, except for the presence of the equatorial 35-methyl on the ligand. The favorable placement of the equatorial 35-methyl group of DTX-1 against the aromatic π-bonds of His191 may account for the increased affinity of PP2A toward DTX-1. In contrast, the axial 35-methyl of DTX-2 caused the side chain of His191 to rotate 140° so that it pointed toward the solvent, thereby opening one end of the hydrophobic binding cage. This rearrangement to accommodate the unfavorable interaction from the axial 35-methyl of DTX-2 reduces the binding energy and appears to be responsible for the reduced affinity of PP2A for DTX-2. These results highlight the potential of molecular modeling studies for understanding the relative toxicity of analogues once the binding site at the molecular target has been properly characterized.

year: 2009

title: Dust from Australia- A reappraisal

authors: Healy, Terry R.

abstract: This paper reviews the meteorological events of October 1928 associated with severe duststorms in Australia and subsequent transport of dust to New Zealand. In the light of contemporary knowledge of the jet streams, and from reappraisal of the original synoptic charts, reported meteorological conditions and press reports pertaining to these duststorms, it is postulated that for dust to be deposited upon New Zealand within 24 hours, of duststorms in Australia it presumably travelled via the jet stream region of the' middle and upper troposphere.

text: Dust from Australia- A reappraisal This paper reviews the meteorological events of October 1928 associated with severe duststorms in Australia and subsequent transport of dust to New Zealand. In the light of contemporary knowledge of the jet streams, and from reappraisal of the original synoptic charts, reported meteorological conditions and press reports pertaining to these duststorms, it is postulated that for dust to be deposited upon New Zealand within 24 hours, of duststorms in Australia it presumably travelled via the jet stream region of the' middle and upper troposphere.

year: 1970

title: Understanding the Happiness of Māori and the Role of Consumption: Experiences of the Millennial Generation

authors: de Thierry, Ebony

subjects: Māori Well-Being

abstract: Happiness is commonly perceived as the ideal state of being for  all of human kind. Although a universal definition of the term remains elusive, happiness is a goal that everybody wants to achieve. In understanding the different aspects that shape happiness, the literature has shown that this can vary depending on the cultural context. As such, this study investigates the essence of happiness as it is experienced by Māori. In understanding the experiences of the Millennial generation, the role that consumption plays is also explored. This group of young adults have been raised in an era when consumerism and cultural revitalisation are the norm.  

This investigation was guided by hermeneutic phenomenology using a kaupapa Māori research perspective. Through this, thirteen young Māori individuals were interviewed to gain their experiences of happiness. Photo elicitation techniques were utilised as a means to facilitate these interviews. Stories of the participants’ experiences of happiness were crafted and then analysed to explore the role of consumption.

Findings show that the happiness of Māori is shaped by the five themes of; sense of belonging, whānau and relationships, spirituality, achievement and success, and sense of freedom. These themes interrelate as they are underpinned by the collective values of Māori. In particular, the aspects of spirituality and sense of belonging appear to be specific to the Māori realm. These are based on customs, values and beliefs that are inherited from our ancestors yet are still prevalent today. In terms of consumption, happiness can be positively linked to experiential consumption. In this case, it can play three different roles on the happiness of Māori through either; a direct connection, an indirect connection, or a negative connection. For Māori, consumption is more likely to have an indirect connection. This implies that it is able to facilitate, maintain and enhance happiness, but is not essential to creating these feelings. This investigation contributes to the literature in four ways. First, this study serves as a starting point to developing a comprehensive framework of happiness that is specific to the culture, views and values of Māori. This will assist Māori through ensuring that they are accurately represented in policies, frameworks and statistics. Second, it proposes five guidelines for Māori which suggest how they can maximise happiness through consumption. Third, this study provides a more up-to-date understanding of the happiness of Māori at the individual level whilst incorporating the impact of collective values. Marketers, researchers and practitioners can utilise this information in an attempt to aid in improving the happiness of Māori society. Finally, it shows that consumption can continue to be positively related to happiness once basic needs have been met. The positive role that consumption can play on happiness is identified, showing that marketers and consumers can work together to achieve happiness.

text: Understanding the Happiness of Māori and the Role of Consumption: Experiences of the Millennial Generation Happiness is commonly perceived as the ideal state of being for  all of human kind. Although a universal definition of the term remains elusive, happiness is a goal that everybody wants to achieve. In understanding the different aspects that shape happiness, the literature has shown that this can vary depending on the cultural context. As such, this study investigates the essence of happiness as it is experienced by Māori. In understanding the experiences of the Millennial generation, the role that consumption plays is also explored. This group of young adults have been raised in an era when consumerism and cultural revitalisation are the norm.  

This investigation was guided by hermeneutic phenomenology using a kaupapa Māori research perspective. Through this, thirteen young Māori individuals were interviewed to gain their experiences of happiness. Photo elicitation techniques were utilised as a means to facilitate these interviews. Stories of the participants’ experiences of happiness were crafted and then analysed to explore the role of consumption.

Findings show that the happiness of Māori is shaped by the five themes of; sense of belonging, whānau and relationships, spirituality, achievement and success, and sense of freedom. These themes interrelate as they are underpinned by the collective values of Māori. In particular, the aspects of spirituality and sense of belonging appear to be specific to the Māori realm. These are based on customs, values and beliefs that are inherited from our ancestors yet are still prevalent today. In terms of consumption, happiness can be positively linked to experiential consumption. In this case, it can play three different roles on the happiness of Māori through either; a direct connection, an indirect connection, or a negative connection. For Māori, consumption is more likely to have an indirect connection. This implies that it is able to facilitate, maintain and enhance happiness, but is not essential to creating these feelings. This investigation contributes to the literature in four ways. First, this study serves as a starting point to developing a comprehensive framework of happiness that is specific to the culture, views and values of Māori. This will assist Māori through ensuring that they are accurately represented in policies, frameworks and statistics. Second, it proposes five guidelines for Māori which suggest how they can maximise happiness through consumption. Third, this study provides a more up-to-date understanding of the happiness of Māori at the individual level whilst incorporating the impact of collective values. Marketers, researchers and practitioners can utilise this information in an attempt to aid in improving the happiness of Māori society. Finally, it shows that consumption can continue to be positively related to happiness once basic needs have been met. The positive role that consumption can play on happiness is identified, showing that marketers and consumers can work together to achieve happiness.

year: 2012