213 research outputs found
Role of WD domain-containing proteins in cell cycle progression
Get PDFIn the eukaryotic proteome, WD domain is one of the most abundant protein motifs. The structure of WD domain allows it to interact with diverse protein partners and proteins containing WD domain have been shown to function in various cellular processes. In this thesis, I describe how two WD domain-containing proteins, LRWD1/ORCA and RFWD3, regulate different aspects of cell cycle progression.
In eukaryotic cells, the duplication of the genome starts from the loading of a six-subunit complex, Origin Recognition Complex (ORC), onto replication origins on the chromosome. The loading of ORC triggers the assembly of the pre-replicative complex (pre-RC) at origins, which licensed the origins prior to entering S phase. Unlike yeast, replication origins in higher eukaryotes do not have consensus sequence and metazoan ORC does not bind to DNA in a specific manner. Thus, a long-standing question in the field has been, how are origins specified and how are ORCs recruited to origins? Studies suggest that ORC loading may be facilitate by ORC-associated proteins. LRWD1/ORCA is an ORC-associated protein that stabilizes ORC on chromatin. We have previously characterized ORCA’s role in replication initiation and heterochromatin organization. In Chapter 2, I describe my work to map the binding sites of ORCA genome-wide by ChIP- seq method at specific time points of G1. ORCA associates with chromatin in a dynamic manner and ORCA binding regions are enriched for heterochromatic marks, including H3K9me3 and methylated-CpGs. ORCA co-localizes with a subset of origins that are enriched for repressive marks, consistent with the fact that these origins replicate late during S phase. Further, ORCA directly associates with the repressive marks and interacts with the enzymes that catalyze these marks. ORCA regulates the level of H3K9me3 and methylated-CpG at its binding sites, suggesting a role of ORCA in maintaining the repressive chromatin marks at its binding sites. Importantly, repressive marks are required for ORCA’s association on chromatin. I propose that ORCA localizes to a subset of origins by association with repressive marks and recruits the enzymes to maintain the repressive chromatin environment.
In Chapter 3, I focus on another WD domain containing protein, RFWD3, and describe how RFWD3 regulates cell cycle progression. Unlike previous studies that described how RFWD3 regulates DNA damage response, I focus on how RFWD3 regulate unperturbed cell cycle progression. I show that RFWD3 is required for proper cell cycle progression. Depletion of RFWD3 causes S phase defects including slower replication fork progression and prolonged S phase. There is also increased loading of replication fork proteins on S phase chromatin in the absence of RFWD3, potentially due to stalled replication fork. RFWD3 associates with the replication fork component, PCNA, via a PIP box motif. I purpose that RFWD3 localizes to replication fork by interacting with PCNA and regulate proper replication fork progression.
In Chapter 4, I summarize my findings on the regulation of DNA replication, chromatin organization and S phase progression. I also discussed interesting areas of research that my work has opened up.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-08-01The student, Yating Wang, accepted the attached license on 2017-07-07 at 10:35.The student, Yating Wang, submitted this Dissertation for approval on 2017-07-07 at 10:47.This Dissertation was approved for publication on 2017-07-09 at 16:22.DSpace SAF Submission Ingestion Package generated from Vireo submission #11332 on 2017-09-29 at 11:14:35Made available in DSpace on 2017-09-29T16:39:20Z (GMT). No. of bitstreams: 2
WANG-DISSERTATION-2017.pdf: 2379470 bytes, checksum: 8df5906ffa8dfc73ce9ad20d8705e304 (MD5)
LICENSE.txt: 4208 bytes, checksum: 4fad10476925e557cb3330ddd2373bd7 (MD5)
Previous issue date: 2017-07-09Embargo set by: Colleen Fallaw for item 103402
Lift date: 2019-09-29T16:39:52Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Colleen Fallaw for item 103402
Lift date: 2019-09-29T17:52:45Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 103402 on 2019-09-30T09:15:17Z
The Role of Long Noncoding RNAs in Cancer and Microbiota-derived Aryl Hydrocarbon Receptor Ligands
Get PDFLncRNAs are a group of non-coding RNAs containing >200 nucleotides and these RNAs have no significant protein coding potential. In the past 10-15 years the role of lncRNAs in cancers have been demonstrated, however, their function in tumors and potential for drug targeting are not well defined. We studied two lncRNAs, HOXA transcript at the distal tip (HOTTIP) and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in pancreatic cancer using the in vitro cell lines and in vivo xenograft or transgenic mouse models. Our results demonstrated that both lncRNAs are pro-oncogenic in the pancreatic cancer, supported by the observation that knockdown of HOTTIP and MALAT1 decreased cell proliferation, migration/invasion and increased apoptosis. HOTTIP might exhibit some pro-oncogenic functions, via the regulation of HOXA gene clusters in a cis-regulating manner. On the other hand, MALAT1 regulate responses of pancreatic cancer cells in part via polycomb repressive complex 2 (PRC2) dependent and independent pathways. Our transcriptomic results support the important but distinct roles of HOTTIP and MALAT1 in pancreatic cancer and we also show that MALAT1 expression can be targeted by small molecule drugs. In the second part of this dissertation, we studied several microbiota-derived aryl hydrocarbon receptor (AhR) ligands. The AhR is a ligand-activated transcription factor with an evolving role in the normal physiological development and diseases. Gut microbiota metabolites are important for mediating communication between gut microflora and the host. It has recently been shown that the gut microbiota produces several metabolites that are AhR ligands. Microbiota-derived tryptophan metabolites and 1,4-dihydroxy-2-napthoic acid (DHNA) and related compounds are reported to be AhR ligands as evidence by their induction of cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and other AhR-responsive genes. We hypothesized the microbiota-derived AhR ligands are selective AhR modulators (sAhRMs) and their induction responses are compound, gene and cell context dependent. We have carried out extensive studies on tryptophan metabolites, DHNA and related compounds in both human and mouse colon cancer cell lines, and have observed that some of these compounds exhibited partial agonist/antagonist activities that are both gene and cell context specific
A Review of Antecedents and Effects of Loyalty on Food Retailers toward Sustainability
Get PDFWith the increase in consumer awareness of sustainability and diversified retailer brands, the conceptualizations and dimensions of brand loyalty are changing. Existing research studies have focused on traditional constructs and measurements to explain new phenomena in the food retail sector but ignored the environmental and social effects on consumers’ attitudinal and behavioral loyalty. This study entails an extensive and structured review of definitions, taxonomy, dimensions, and measurements of loyalty within a food marketing context. With an additional emphasis on the notion of sustainability, it provides a perspective theory synthesis that integrates all testified antecedents of all types of loyalty to emphasize a trend of sustainability beyond brand scope, whereby sustainability values create loyalty. A systematic literature review and qualitative analysis methods were used to identify the relevant literature. The studies that qualified for inclusion were those that reported (1) research methods, (2) dimensions of brand loyalty, (3) knowledge of sustainability factors, and (4) organic marketing. This paper summarizes and compares the key constructs and measurements of loyalty to retailers. The results show inconsistencies in relation to two important attitudinal dimensions, namely, brand satisfaction and brand value. Although loyalty towards product brands, loyalty toward service organizations, store loyalty, and retailer loyalty have been studied in recent decades by marketing academics, little attention has been paid to clarifying their role in food retailing, especially regarding whether the established dimensions are relevant in conceptualizing consumer loyalty in sustainability based on organic food marketing. The theoretical implications are discussed in association with the research gap between loyalty dimensions and sustainability values, as well as multidimensional measurements development. The practical implications of this review are important for food retailers and organic food marketers that can meet the satisfaction and retain consumers’ loyalty by providing organic and sustainable products and improving related service quality involving environmental consequences and social well-being
Mapping the Intellectual Linkage of Sustainability in Marketing
Get PDFThis study explores the status quo regarding the interface between marketing, social and environmental issues, culture and consumers, and strategic management by integrating sustainability. A qualitative display network technique, based on the bibliometric methodology of co-citation analysis, was applied to examine research clusters. An integrative review was conducted to explain the connections within these clusters. To evaluate potential patterns among the studies through citations, different sets of relationships among applicable sustainability theories in marketing practice were paired in different sets and analyzed. After mapping the scientific structure of journal publications and intellectual linkages, six cluster groups emerged, reflecting the important role of marketing in linking sustainability, society, environment, consumers, and corporate sustainable development. This study contributes to social and marketing research and corporate sustainability practice by categorizing the intellectual structural network within various streams and indicating the influence of social and cultural notions on consumer-focused sustainable marketing
The influence of sustainable design on food well-being
No full textPurpose – This study investigates the effects of sustainable design on food policy, literacy, and socialisation to gauge consumers’ satisfaction with the general design of food well-being (FWB). Design/methodology/approach – Using data from an online survey with 382 respondents, an empirical study applying composite-based structural equation modelling was conducted. Sustainable design for food socialisation was hypothesised to directly influence consumers’ satisfaction with the general design of FWB, whereas food policy was assumed to have an emergent effect on food literacy. Gender was a control variable used to identify the heterogeneity of the effects. Findings – The results demonstrated that sustainable design for food policy and food literacy positively influence food socialisation and affect consumers’ satisfaction with the sustainable design for FWB. Additionally, women exhibited higher application of food knowledge and skills but less experience in FWB than men. Originality/value – To the best of the authors knowledge, this study is the first to examine the emergent influence of food policy from a design perspective, with implications for industrial practitioners, policymakers, and academic research. This study also provides possible avenues for future sustainability and food product design research
A food well-being index for sustainable eating behavior:Construction, validation, and implementation
Get PDFFood well-being is critical in food marketing and sustainability, yet identifying its key sources and validating them against overall well-being remains challenging. Food marketers struggle to assess contributable factors in strategic decisions. Enhancing food well-being boosts consumer happiness and sustainability, but lacks a standardized evaluation method. This study introduces a novel Food Well-Being Index (FWBI) embedded in a nomological net using composite-based structural equation modeling to identify key sources of consumer happiness and compare performance across composite variables to promote healthier and more sustainable eating habits. Data from 401 participants are analyzed using partial least squares structural equation modeling. Participants provide ratings on 56 statements in the questionnaire, forming the basis for the indicators. An importance-performance matrix analysis is applied to capture important indicators and their performances. Results reveal individual and environmental well-being as the most salient drivers of food-related happiness, while social well-being demonstrates higher performance. These dimensions are underpinned by motivations for health and environmental responsibility and moderating food well-being to encourage sustainable consumption behaviors. This empirical study contributes to marketing research and practice in three ways. First, it calibrates the FWBI and identifies key indicators of food well-being. Second, it validates the relevance of food well-being and its impact on overall well-being. Third, it conducts an importance-performance matrix analysis, illustrating how managers in different sectors can use the FWBI to identify essential aspects in food production, design, and retailing, and improve products and services. Therefore, this study has significant implications for sustainability-oriented marketing strategies.</p
Integrating sustainability into food marketing:A design-based extension of the food well-being paradigm
Get PDFThis dissertation examines the integration of sustainability in food marketing from three core perspectives: food retailers, food manufacturers and producers, and consumers. It explores how these perspectives can shape consumer eating behaviors to promote contributions to society and the environment, ultimately advancing key indicators that promote food well-being towards sustainability. Although the importance of food well-being has grown in recent decades, its conceptualization remains hindered by a lack of coherent frameworks and standardized measures. This study proposes a consumer-centric, bottom-up approach to sustainability marketing, which underscores consumer benefits while aligning with broader sustainability goals. To advance this agenda, the research posits an expanded paradigm of food well-being, redefining it as a holistic concept that integrates individual, societal, environmental, and economic dimensions. This refined concept seeks to align consumer-driven preferences with broader societal and environmental contributions, creating a synergistic path toward sustainable food systems.By validating and implementing the Food Well-Being Index (FWBI) through Composite-Based Structural Equation Modeling (cSEM), the dissertation makes significant contributions to both theoretical advancements and practical applications within food retailing, manufacturing, product design, food service, and consumer behavior domains. It demonstrates how researchers and food marketing practitioners can integrate sustainability into food marketing practices, establishing the FWBI as a composite measure encompassing individual, social, environmental, and economic dimensions of well-being. The research consists of five independent studies, each focusing on distinct facets of food well-being and sustainability in marketing, thereby providing a comprehensive framework for understanding and applying the FWBI across diverse food industry contexts.<br/
- …
