We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the approximately 160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates and frequently carries oncogenic KRAS mutation. However, KRAS has thus far not been a viable therapeutic target. We found that the abundance of YAP mRNA, which encodes Yes-associated protein (YAP), a protein regulated by the Hippo pathway during tissue development and homeostasis, was increased in human PDAC tissue compared with that in normal pancreatic epithelia. In genetically engineered KrasG12D and KrasG12D: Trp53R172H mouse models, pancreas-specific deletion of Yap halted the progression of early neoplastic lesions to PDAC without affecting normal pancreatic development and endocrine function. Although Yap was dispensable for acinar to ductal metaplasia (ADM), an initial step in the progression to PDAC, Yap was critically required for the proliferation of mutant Kras or Kras:Trp53 neoplastic pancreatic ductal cells in culture and for their growth and progression to invasive PDAC in mice. Yap functioned as a critical transcriptional switch downstream of the oncogenic KRAS–mitogen-activated protein kinase (MAPK) pathway, promoting the expression of genes encoding secretory factors that cumulatively sustained neoplastic proliferation, a tumorigenic stromal response in the tumor microenvironment, and PDAC progression in Kras and Kras: Trp53 mutant pancreas tissue. Together, our findings identified Yap as a critical oncogenic KRAS effector and a promising therapeutic target for PDAC and possibly other types of KRAS-mutant cancers.
This article explores how neutralisation can explain people’s lack of commitment to buying Fair Trade (FT) products, even when they identify FT as an ethical concern. It examines the theoretical tenets of neutralisation theory and critically assesses its applicability to the purchase of FT products. Exploratory research provides illustrative examples of neutralisation techniques being used in the FT consumer context. A conceptual framework and research propositions delineate the role of neutralisation in explaining the attitude-behaviour discrepancies evident in relation to consumers’ FT purchase behaviour, providing direction for further research that will generate new knowledge of consumers’ FT purchase behaviour and other aspects of ethical consumer behaviour. Copyright Springer Science+Business Media B.V. 2007attitude-behaviour gap, ethical consumerism, ethical decision-making, fair trade purchase, neutralisation,
This paper applies the persuasion knowledge model to explain consumers' responses to charity guilt appeals. With data obtained through a stimuli-driven survey, the research examines the relationships between knowledge of persuasion tactics and charities, and the level of felt guilt experienced in response to an advertisement and subsequent donation intentions. The findings show that guilt arousal is positively related to donation intention, and that persuasion and agent knowledge impact the extent of guilt aroused. The research confirms that consumers are active rather than passive processors of marketing communications by revealing the role of persuasion and agent knowledge as methods of coping with and informing responses to guilt appeals. Specifically, the research finds that manipulative intent and the respondents' skepticism toward advertising tactics in general are negatively related to guilt arousal but that their affective evaluation and beliefs about a charity are positively related to feelings of guilt. However, it also shows that there is a positive direct relationship between perceived manipulative intent and the intention to donate.
Consumer demand for counterfeit luxury brands is unethical, but it is also robust and growing. The aim of this exploratory research, which employs in-depth interviews, is twofold: 1) to identify the psychological and emotional insights that drive and result from the consumption of higher involvement counterfeit goods; and 2) to uncover the coping strategies related to unethical counterfeit consumption. This research reveals new psychological motivations (e.g., "thrill of the hunt", being part of a "secret society" and genuine interest) underlying counterfeit consumption and the associated emotional outcomes (e.g., embarrassment, shame and positive hedonic gains). This research is also one of the few studies to identify cognitive moral logics by disclosing the neutralization techniques (specifically denial of responsibility and appealing to higher loyalties) that consumers adopt to cope with the cognitive dissonance associated with debatable counterfeit consumption. The paper contributes to scholarly, managerial and policy conversations.
BackgroundThe major human intestinal pathogen Giardia lamblia is a very early branching eukaryote with a minimal genome of broad evolutionary and biological interest.ResultsTo explore early kinase evolution and regulation of Giardia biology, we cataloged the kinomes of three sequenced strains. Comparison with published kinomes and those of the excavates Trichomonas vaginalis and Leishmania major shows that Giardia's 80 core kinases constitute the smallest known core kinome of any eukaryote that can be grown in pure culture, reflecting both its early origin and secondary gene loss. Kinase losses in DNA repair, mitochondrial function, transcription, splicing, and stress response reflect this reduced genome, while the presence of other kinases helps define the kinome of the last common eukaryotic ancestor. Immunofluorescence analysis shows abundant phospho-staining in trophozoites, with phosphotyrosine abundant in the nuclei and phosphothreonine and phosphoserine in distinct cytoskeletal organelles. The Nek kinase family has been massively expanded, accounting for 198 of the 278 protein kinases in Giardia. Most Neks are catalytically inactive, have very divergent sequences and undergo extensive duplication and loss between strains. Many Neks are highly induced during development. We localized four catalytically active Neks to distinct parts of the cytoskeleton and one inactive Nek to the cytoplasm.ConclusionsThe reduced kinome of Giardia sheds new light on early kinase evolution, and its highly divergent sequences add to the definition of individual kinase families as well as offering specific drug targets. Giardia's massive Nek expansion may reflect its distinctive lifestyle, biphasic life cycle and complex cytoskeleton.
This paper explores consumer understanding and perception of organic food, with specific reference to the relatively new concept of organic farmed salmon. Key themes associated with the term “organic” and its meaning, as determined by consumers, are explored and the role of labelling and regulatory authorities considered. Focus groups in five countries (UK, Germany, Spain, Norway and France) consisting of 196 participants showed that most consumers are confused about the meaning of the term organic and are largely unaware of the organic certification and labelling process. Many consumers were unsure, even sceptical about the concept of organic farmed salmon and display a large amount of distrust in the regulatory process. The implications for the concept of organic food and salmon production and directions for further research are discussed.
This paper investigates the role of emotion in the ethical choice processes of tourists. Specifically, it explores how hedonism is experienced and the links between hedonic experiences and intentions for future ethical behaviour. It adopts an interpretative phenomenological analysis (IPA) approach to examine the experience of emotion in self-defined ethical tourists' consumption of places. The findings highlight that emotionally charged experiences are powerful motivators of consumers' ethical choice. It identifies the role hedonism plays in rationalizing and reinforcing current and intended ethical behaviour. Finally, the paper discusses the importance of emotional experiences as a source of hedonic value in engaging individuals in consumption encounters.
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