586 research outputs found

    Single-cell analysis of cardiogenesis reveals basis for organ-level developmental defects.

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    Organogenesis involves integration of diverse cell types; dysregulation of cell-type-specific gene networks results in birth defects, which affect 5% of live births. Congenital heart defects are the most common malformations, and result from disruption of discrete subsets of cardiac progenitor cells1, but the transcriptional changes in individual progenitors that lead to organ-level defects remain unknown. Here we used single-cell RNA sequencing to interrogate early cardiac progenitor cells as they become specified during normal and abnormal cardiogenesis, revealing how dysregulation of specific cellular subpopulations has catastrophic consequences. A network-based computational method for single-cell RNA-sequencing analysis that predicts lineage-specifying transcription factors2,3 identified Hand2 as a specifier of outflow tract cells but not right ventricular cells, despite the failure of right ventricular formation in Hand2-null mice4. Temporal single-cell-transcriptome analysis of Hand2-null embryos revealed failure of outflow tract myocardium specification, whereas right ventricular myocardium was specified but failed to properly differentiate and migrate. Loss of Hand2 also led to dysregulation of retinoic acid signalling and disruption of anterior-posterior patterning of cardiac progenitors. This work reveals transcriptional determinants that specify fate and differentiation in individual cardiac progenitor cells, and exposes mechanisms of disrupted cardiac development at single-cell resolution, providing a framework for investigating congenital heart defects

    How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

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    This work was financially support by a Marie Curie Initial Training Network grant, “Understanding the evolutionary origin of biological diversity” (ITN-2008–213780 SPECIATION), grants from the Academy of Finland to A.H. (project 132619) and M.K. (projects 268214 and 272927), a grant from NERC, UK to M.G.R. (grant NE/J020818/1), and NERC, UK PhD studentship to D.J.P. (NE/I528634/1).For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.PostprintPeer reviewe

    Self-identity and consumption : a study of consumer personality, brand personality, and brand relationship

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    This thesis investigates the relationship between self-identity and consumption by discussing the conceptual and measurement issues of consumer personality, brand personality, and brand relationship. The investigation is based on the theories of personality, self-identity, and interpersonal relationship. The self-identity theories (Belk 1988; Cooley 1964; James 1890; Mead 1935) suggest that consumers may use brands to construct, maintain, and enhance their self-identities. Drawing from the literature of personality and self-identity, this thesis repositions the concept of personality for the context of consumption and refers it to self-identity (self-perception) rather than behaviour. This repositioning indicates that consumer personality and brand personality can be examined by the same personality concept. On the basis of the self-identity theories, a positive relationship is expected to exist between consumer personality and brand personality. Moreover, the interpersonal relationship theories (Aron et al. 1991; Rodin 1978; Thibaut and Kelley 1959) indicate that the relationship partners become a part of the self-identity in a close relationship. Therefore, it is hypothesised that the closer the brand personality and consumer personality perceived by the consumers (consumer-brand congruence), the better the brand relationship quality. This study applies a quasi-experiment from a field setting to examine the relationship among consumer personality, brand personality, and brand relationship. A 2 (high and low involvement) x 2 (high and low feeling) factorial design is featured to explore the role of involvement and feeling in the relationship of self-identity and consumption. A total number of 468 observations reveals that consumer and brand personality are strongly and positively related. The greater the consumer-brand congruence is, the better the brand relationship. Minimal moderating effects of involvement and feeling to the relationships between consumer personality and brand personality and between consumer-brand congruence and brand relationship quality are observed. These findings suggest that consumers use brands from various product categories in different situations to maintain their self-identities. The study attempts to make contributions on the theoretical, methodological, and managerial levels. Theoretically, it clarifies the concepts of consumer personality and brand personality, and reaffirms the concept of brand relationship. In this way, some measurement issues of self-identity and brand personality are resolved. The findings suggest that brand personality can be used as a tool to investigate global markets and to facilitate market segmentation and communication. Finally, the limitations of the thesis are recognised and directions for future research are offered

    Quadruplex DNA: sequence, topology and structure.

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    G-quadruplexes are higher-order DNA and RNA structures formed from G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Potential quadruplex sequences have been identified in G-rich eukaryotic telomeres, and more recently in non-telomeric genomic DNA, e.g. in nuclease-hypersensitive promoter regions. The natural role and biological validation of these structures is starting to be explored, and there is particular interest in them as targets for therapeutic intervention. This survey focuses on the folding and structural features on quadruplexes formed from telomeric and non-telomeric DNA sequences, and examines fundamental aspects of topology and the emerging relationships with sequence. Emphasis is placed on information from the high-resolution methods of X-ray crystallography and NMR, and their scope and current limitations are discussed. Such information, together with biological insights, will be important for the discovery of drugs targeting quadruplexes from particular genes

    Limited-edition advertising does not always work for luxury brands: The influence of consumption contexts

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    Limited-edition advertising on a limited quantity available to be sold (LQS, limited quantity scarcity) is used to increase product value, thereby enticing consumers. This type of limited-edition advertising has been proven to be effective for luxury brands; as a result, its adoption has increased over the years. However, are limited editions effective across all consumption situations? The current study argues that limited-edition advertising may not always work as well as previously thought and that it is only effective when (1) consumers are in emotional (versus cognitive) consumption contexts, (2) the consumption is socially visible (versus invisible), and (3) the country of origin where the luxury product was made is favourable (versus unfavourable). The results of two experiments using 807 participants confirmed the study’s hypotheses. More importantly, the findings showed that limited-edition advertising had detrimental effects in a cognitive consumption context; that is, using limited-edition advertising in a cognitive consumption context decreased consumers’ purchase intentions. Theoretical and managerial implications are discussed

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Self-identity and consumption : a study of consumer personality, brand personality, and brand relationship

    Get PDF
    This thesis investigates the relationship between self-identity and consumption by discussing the conceptual and measurement issues of consumer personality, brand personality, and brand relationship. The investigation is based on the theories of personality, self-identity, and interpersonal relationship. The self-identity theories (Belk 1988; Cooley 1964; James 1890; Mead 1935) suggest that consumers may use brands to construct, maintain, and enhance their self-identities. Drawing from the literature of personality and self-identity, this thesis repositions the concept of personality for the context of consumption and refers it to self-identity (self-perception) rather than behaviour. This repositioning indicates that consumer personality and brand personality can be examined by the same personality concept. On the basis of the self-identity theories, a positive relationship is expected to exist between consumer personality and brand personality. Moreover, the interpersonal relationship theories (Aron et al. 1991; Rodin 1978; Thibaut and Kelley 1959) indicate that the relationship partners become a part of the self-identity in a close relationship. Therefore, it is hypothesised that the closer the brand personality and consumer personality perceived by the consumers (consumer-brand congruence), the better the brand relationship quality. This study applies a quasi-experiment from a field setting to examine the relationship among consumer personality, brand personality, and brand relationship. A 2 (high and low involvement) x 2 (high and low feeling) factorial design is featured to explore the role of involvement and feeling in the relationship of self-identity and consumption. A total number of 468 observations reveals that consumer and brand personality are strongly and positively related. The greater the consumer-brand congruence is, the better the brand relationship. Minimal moderating effects of involvement and feeling to the relationships between consumer personality and brand personality and between consumer-brand congruence and brand relationship quality are observed. These findings suggest that consumers use brands from various product categories in different situations to maintain their self-identities. The study attempts to make contributions on the theoretical, methodological, and managerial levels. Theoretically, it clarifies the concepts of consumer personality and brand personality, and reaffirms the concept of brand relationship. In this way, some measurement issues of self-identity and brand personality are resolved. The findings suggest that brand personality can be used as a tool to investigate global markets and to facilitate market segmentation and communication. Finally, the limitations of the thesis are recognised and directions for future research are offered.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    The Role of Digital-Media-Based Pedagogical Aids in Elementary Entomology: An Innovative and Sustainable Approach

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    It has been challenging for city school pupils to learn about insects, given the lack of live insects. To overcome this challenge, the objective of this study is to propose the use of emerging digital media, namely three-dimensional printing (3DP) technologies, to create reusable, fake, “live” insects. In this study, we designed two 3D-printed pedagogical aids to support elementary entomology. The first aid was a set of cards showing photos of the 3D-printed insect prototype, which could help the learners in close observation of the insect body’s regions and parts, and the second 3D-printed aid was a construction kit mimicking physical insects, which were made of an enlarged 3D-printed insect prototype. The two aids were used in our field experiment to examine the effectiveness in learning and motivation. A total of 153 pupils were grouped into three groups (one using the existing multimedia e-book, one using the first 3DP aid, and one using the second aid). The results confirm that the digital media application—in this case, 3DP technologies—were able to compensate for the lack of the live insects. These results raised our confidence in using a customized size 3D-printed insect prototype to enhance rudimentary entomology inside the classroom. If the 3DP technologies are used properly, they could offer an innovative and sustainable solution

    Emerging roles and competencies of district and sub-district pharmacists: a case study from Cape Town

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    District and sub-district pharmacist positions were created during health sector reform in South Africa. High prevalence of HIV/AIDS, tuberculosis and increasing chronic non-communicable diseases have drawn attention to their pivotal roles in improving accessibility and appropriate use of medicines at the primary level. This research describes new roles and related competencies of district and sub-district pharmacists in Cape Town. Between 2008 and 2011, the author (HB) conducted participatory action research in Cape Town Metro District, an urban district in the Western Cape Province of South Africa, partnering with pharmacists and managers of the two government primary health care (PHC) providers. The two providers function independently delivering complementary PHC services across the entire geographic area, with one provider employing district pharmacists and the other sub-district pharmacists. After an initiation phase, the research evolved into a series of iterative cycles of action and reflection, each providing increasing understanding of district and sub-district pharmacists’ roles and competencies. Data was generated through workshops, semi-structured interviews and focus groups with pharmacists and managers which were recorded and transcribed. Thematic analysis was carried out iteratively during the 4-year engagement and triangulated with document reviews and published literature. Five main roles for district and sub-district pharmacists were identified: district/sub-district management; planning, co-ordination and monitoring of pharmaceuticals; information and advice; quality assurance and clinical governance; and research (district pharmacists)/dispensing at clinics (sub-district pharmacists). Although the roles looked similar, there were important differences, reflecting the differing governance and leadership models and services of each provider. Five competency clusters were identified: professional pharmacy practice; health system and public health; management; leadership; and personal, interpersonal and cognitive competencies. Whilst professional pharmacy competencies were important, generic management and leadership competencies were considered critical for pharmacists working in these positions. Similar roles and competencies for district and sub-district pharmacists were identified in the two PHC providers in Cape Town, although contextual factors influenced precise specifications. These insights are important for pharmacists and managers from other districts and sub-districts in South Africa and inform health workforce planning and capacity development initiatives in countries with similar health systems.Web of Scienc
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