A Characterization of Substrates and Factors Involved in Yeast Nonsense-Mediated mRNA Decay: A Dissertation

Many intricate and highly conserved mechanisms have evolved to safeguard organisms against errors in gene expression. The nonsense-mediated mRNA decay pathway (NMD) exemplifies one such mechanism, specifically by eliminating mRNAs containing premature translation termination codons within their protein coding regions, thereby limiting the synthesis of potentially deleterious truncated polypeptides. Studies in Saccharomyces Cerevisiae have found that the activity of at least three trans-acting factors, known as UPF1, UPF2/NMD2, and UPF3is necessary for the proper function of the NMD pathway. Further research conducted in yeast indicates that the degradation of substrates of the NMD pathway is dependent on their translation, and that the sub-cellular site of their degradation in the cytoplasm. Although most evidence in yeast suggests that substrates of the NMD pathway are degraded in the cytoplasm while in association with the translation apparatus, some mammalian studies have found several mRNAs whose decay appears to occur within the nucleus or before their transport to the cytoplasm has been completed. In addition, study of the mammalian TPI mRNA found that this transcript was unavailable as a substrate for the NMD pathway once it had been successfully exported to the cytoplasm, further supporting the notion that the degradation of mammalian substrates of the NMD pathway occurs in association with the nucleus, or during export from the nucleus to the cytoplasm. To determine if yeast cytoplasmic nonsense-containing mRNA can become immune to the NMD pathway we examined the decay kinetics of two NMDS substrate mRNAs in response to repressing or activating the NMD pathway. Both the ade2-1 and pgk1-UAG-2nonsense-containing mRNAs were stabilized by repressing this pathway, while activation of NMD resulted in the rapid and immediate degradation of each transcripts. These findings demonstrate that nonsense-containing mRNAs residing in the nucleus are potentially susceptible to NMD at each round of translation. The remainder of this thesis utilizes protein overexpression studies to gain understanding into the function of factors related to the processes of nonsense-mediated mRNA decay and translation in Saccharomyces cerevisiae. Overexpression of a C-terminal truncated form of Nmd3p was found to be dominant-negative for cell viability, translation and the normal course of rRNA biogenesis. Overexpression studies conducted with mutant forms of the nonsense-mediated mRNA decay protein Upf1p, found that overexpression of mutants in the ATP binding and ATP hydrolysis region ofUpflp were dominant-negative for growth in an otherwise wild-type yeast strain. Furthermore, overexpression of the ATP hydrolysis mutant of Upf1p (DE572AA), resulted in the partial inhibition of NMD and a general perturbation of the translation apparatus. These results support previous studies suggesting a general role for Upf1p function in translation

Luxury branding below the radar

For nearly a decade marketers have been talking about the rise of “inconspicuous consumption”: elite consumers’ growing affinity for discreet rather than traditionally branded luxuries

Crescent marketing, Muslim geographies and brand Islam: reflections from the JIMA Senior Advisory Board

Purpose – To bring together the thoughts and opinions of key members of the Journal of Islamic Marketing’s (JIMA) Editorial Team, regarding the recently branded phenomenon of Islamic marketing - in the interests of stimulating further erudition. Design/methodology/approach – The authors adopted an ‘eagle eye’ method to investigate this phenomenon: Where attempts were made to frame general principles and observations; alongside a swooping view of key anecdotal observations - in order to ground and enrich the study. We participated in an iterative process when analysing longitudinal and contemporary phenomenological data, in order to arrive at a consensus. This was grounded in: Triangulating individual and collective researcher findings; critiquing relevant published material; and reflecting upon known reviewed manuscripts submitted to marketing publications – both successful and unsuccessful. Findings – We assert that a key milestone in the study and practice of marketing, branding, consumer behaviour and consumption in connection with Islam and Muslims is the emergence of research wherein the terms “Islamic marketing” and “Islamic branding” have evolved – of which JIMA is also a by-product. Some have construed Islam marketing/branding as merely a niche area. Given the size of Muslim populations globally and the critical importance of understanding Islam in the context of business and practices with local, regional and international ramifications, scholarship on Islamic marketing has become essential. Western commerce and scholarship has been conducted to a limited extent, and some evidence exists that research is occurring globally. We believe it is vital for “Islamic marketing” scholarship to move beyond simply raising the flag of ‘Brand Islam’ and the consideration of Muslim geographies to a point where Islam – as a way of life, a system of beliefs and practices, and religious and social imperatives – is amply explored. Research limitations/implications – An ‘eagle eye’ view has been taken, which balances big picture and grassroots conceptual findings. The topic is complex – and so while diverse expert opinions are cited, coverage of many issues is necessarily brief, due to space constraints. Practical implications – Scholars and practitioners alike should find the thoughts contained in the paper of significant interest. Ultimately, scholarship of Islam’s influences on marketing theory and practice should lead to results which have pragmatic implications, just as research on Islamic banking and finance has. Originality/value – The paper appears to be the first to bring together such a diverse set of expert opinions within one body of work, and one that provides a forum for experts to reflect and comment on peers’ views, through iteration. Also the term Crescent marketing is introduced to highlight how critical cultural factors are, which shape perceptions and Islamic practises

Cyber peers’ influence for adolescent consumer in decision-making styles and online purchasing behavior

[[abstract]]Nowadays, there is a boom in online purchasing, especially by adolescents. In fact, scholars and marketers alike have long noticed the emergence of adolescent consumers and their consumption behaviors. This research aims at exploring the effect of adolescent decision-making styles on online purchasing behavior, with peer influence as a moderating variable. An online questionnaire survey was conducted on 2,419 adolescents and further verified by regression analysis and analysis of covariance. Adolescents with planned purchase behaviors can be considered as rational consumers, in that they do not care about fashion, or recreational, hedonistic shopping consciousness, but rather focus on brand, price value, and high quality. Indeed, adolescent purchase decision making can be strengthened by peer influence.[[journaltype]]國外[[incitationindex]]SSCI[[ispeerreviewed]]Y[[booktype]]電子版[[booktype]]紙本[[countrycodes]]US

The rise of inconspicuous consumption

Ever since Veblen and Simmel, luxury has been synonymous with conspicuous consumption. In this conceptual paper we demonstrate the rise of inconspicuous consumption via a wide-ranging synthesis of the literature. We attribute this rise to the signalling ability of traditional luxury goods being diluted, a preference for not standing out as ostentatious during times of economic hardship, and an increased desire for sophistication and subtlety in design in order to further distinguish oneself for a narrow group of peers. We decouple the constructs of luxury and conspicuousness, which allows us to reconceptualise the signalling quality of brands and the construct of luxury. This also has implications for understanding consumer behaviour practices such as counterfeiting and suggests that consumption trends in emerging markets may take a different path from the past

Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope overlapping the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses

The rise of inconspicuous consumption

Inconspicuous consumption – where brand signals are not readily apparent, available or visible to most consumers – is on the rise, even in Asia, which has typically favored conspicuous brand signaling. This appears to be an oxymoron which challenges conventional branding theory; we argue it’s redefining constructs such as luxury and class

Islamic Arab hospitality and multiculturalism

This ethnographic study in Qatar and United Arab Emirates addresses a particular Islamic consumptionscape as well as a related commodified practice: that of Arab hospitality. This much vaunted Arab virtue is examined in three contexts: home hospitality, commercial hospitality, and hospitality toward foreign guest workers and visitors. We find that home hospitality is largely extended inward and involves sharing in with close same-sex friends and family in a tournament of status, while hospitality toward foreigners is largely either nonexistent or outsourced to other foreigners. These patterns are explained in terms of hyper-ritualization of that which is most in doubt, namely, multiculturalism and patriarchal authority. We argue that this same pattern of hyper-ritualization may apply in other ritual contexts like American Thanksgiving celebrations