Decoding development inXenopus tropicalis

Xenopus tropicalis is rapidly being adopted as a model organism for developmental biology research and has enormous potential for increasing our understanding of how embryonic development is controlled. In recent years there has been a well-organized initiative within the Xenopus community, funded largely through the support of the National Institutes of Health in the US, to develop X. tropicalis as a new genetic model system with the potential to impact diverse fields of research. Concerted efforts have been made both to adapt established methodologies for use in X. tropicalis and to develop new techniques. A key resource to come out of these efforts is the genome sequence, produced by the US Department of Energy’s Joint Genome Institute and made freely available to the community in draft form for the past three years. In this review, we focus on how advances in X. tropicalis genetics coupled with the sequencing of its genome are likely to form a foundation from which we can build a better understanding of the genetic control of vertebrate development and why, when we already have other vertebrate genetic models, we should want to develop genetic analysis in the frog

T-box genes in early embryogenesis

The T-box gene family, encoding related DNA-binding transcriptional regulators, plays an essential role in controlling many aspects of embryogenesis in a wide variety of organisms. The T-box genes exhibit diverse patterns of spatial and temporal expression in the developing embryo, and both genetic and molecular embryological studies have demonstrated their importance in regulating cell fate decisions that establish the early body plan, and in later processes underlying organogenesis. Despite these studies, little is known of either the regulation of the T-box genes or the identities of their transcriptional targets. The aim of this review is to examine the diverse yet conserved roles of several T-box genes in regulating early patterning in chordates and to discuss possible mechanisms through which this functional diversity might arise

Developmental expression patterns ofTbx1,Tbx2,Tbx5, andTbx20 inXenopus tropicalis

T-box genes have diverse functions during embryogenesis and are implicated in several human congenital disorders. Here, we report the identification, sequence analysis, and developmental expression patterns of four members of the T-box gene family in the diploid frog Xenopus tropicalis. These four genes—Tbx1, Tbx2, Tbx5, and Tbx20—have been shown to influence cardiac development in a variety of organisms, in addition to their individual roles in regulating other aspects of embryonic development. Our results highlight the high degree of evolutionary conservation between orthologs of these genes in X. tropicalis and other vertebrates, both at the molecular level and in their developmental expression patterns, and also identify novel features of their expression. Thus, X. tropicalis represents a potentially valuable vertebrate model in which to further investigate the functions of these genes through genetic approaches

Xenopus: An emerging model for studying congenital heart disease

Congenital heart defects affect nearly 1% of all newborns and are a significant cause of infant death. Clinical studies have identified a number of congenital heart syndromes associated with mutations in genes that are involved in the complex process of cardiogenesis. The African clawed frog, Xenopus, has been instrumental in studies of vertebrate heart development and provides a valuable tool to investigate the molecular mechanisms underlying human congenital heart diseases. In this review, we discuss the methodologies that make Xenopus an ideal model system to investigate heart development and disease. We also outline congenital heart conditions linked to cardiac genes that have been well-studied in Xenopus and describe some emerging technologies that will further aid in the study of these complex syndromes

A Comparative Survey of the Frequency and Distribution of Polymorphism in the Genome of Xenopus tropicalis

Naturally occurring DNA sequence variation within a species underlies evolutionary adaptation and can give rise to phenotypic changes that provide novel insight into biological questions. This variation exists in laboratory populations just as in wild populations and, in addition to being a source of useful alleles for genetic studies, can impact efforts to identify induced mutations in sequence-based genetic screens. The Western clawed frog Xenopus tropicalis (X. tropicalis) has been adopted as a model system for studying the genetic control of embryonic development and a variety of other areas of research. Its diploid genome has been extensively sequenced and efforts are underway to isolate mutants by phenotype- and genotype-based approaches. Here, we describe a study of genetic polymorphism in laboratory strains of X. tropicalis. Polymorphism was detected in the coding and non-coding regions of developmental genes distributed widely across the genome. Laboratory strains exhibit unexpectedly high frequencies of genetic polymorphism, with alleles carrying a variety of synonymous and non-synonymous codon substitutions and nucleotide insertions/deletions. Inter-strain comparisons of polymorphism uncover a high proportion of shared alleles between Nigerian and Ivory Coast strains, in spite of their distinct geographical origins. These observations will likely influence the design of future sequence-based mutation screens, particularly those using DNA mismatch-based detection methods which can be disrupted by the presence of naturally occurring sequence variants. The existence of a significant reservoir of alleles also suggests that existing laboratory stocks may be a useful source of novel alleles for mapping and functional studies

Barriers to the use of personal health records by patients: a structured review

Introduction An increasing focus on personal electronic health records (PHRs) offers healthcare benefits for patients, particularly those in undeserved and marginalised populations, who are at risk of receiving less effective healthcare, and may have worse health outcomes. However, PHRs are likely to favour text, technical and health literate users, and be less suitable for disadvantaged patients. These concerns have prompted this review of the literature, which seeks evidence about barriers to the adoption and continued use of PHRs, the nature of the evidence for those barriers, and the stage of PHR implementation where particular barriers apply. Methods Searches in PubMed, Embase, CINAHL and ProQuest databases were used to retrieve articles published in English after 2003 in a refereed journal, or presented in a refereed conference or scientific meeting. After screening to remove items which were out of scope, the phase of the PHR implementation, the type of investigation, and PHR barriers were categorised using thematic coding. Results The search retrieved 395 items; screening identified 34 in-scope publications, which provided evidence of 21 identified barriers to patient adoption and continued use of PHRs, categorised here as Individual, Demographic, Capability, Health-related, PHR or Attitudinal factors. Barriers were identified in most phases of PHR implementation, and in most types of study. A secondary outcome identified that eleven of the publications may have introduced a bias by excluding participants who were less affluent, less capable, or marginalised. Conclusions PHR barriers can interfere with the decision to start using a PHR, with the adoption process, and with continued use, and the impact of particular barriers may vary at different phases of PHR adoption. The complex interrelationships which exist between many of the barriers is suggested in some publications, and emerges more clearly from this review. Many PHR barriers appear to be related to low socioeconomic status. A better understanding is needed of how the effect of barriers is manifested, how that effect can be countered, and how planning and implementation of PHR initiatives can make allowance for patient level barriers to PHR adoption and use, with appropriate actions to mitigate the effect of those barriers for more disadvantaged patients

Theory and Practice in Digital Behaviour Change: A Matrix Framework for the Co-Production of Digital Services That Engage, Empower and Emancipate Marginalised People Living with Complex and Chronic Conditions

Background: The WHO framework on integrated people-centred health services promotes a focus on the needs of people and their communities to empower them to have a more active role in their own health. It has advocated five strategies including: Engaging and empowering people and communities; co-ordinating services within and across sectors; and, creating an enabling environment. Any implementation of these strategies needs to occur at individual, community, and health service levels. Useful steps to reorganising health service provision are already being guided by existing models of care linked to increased adoption and use of digital technologies with examples including: Wagner’s Chronic Care Model (CCM); Valentijn’s Rainbow Model of Integrated Care (RMIC); and Phanareth’s et al.’s Epital Care Model (ECM). However, what about individuals and the communities they live in? How will strategies be implemented to address known inequities in: the social determinants of health; access to, and use of digital technologies, and individual textual, technical, and health literacies? Proposal of a matrix framework: This paper argues that people with complex and chronic conditions (PwCCC) living in communities that are at risk of being under-served or marginalised in health service provision require particular attention. It articulates a step-by-step process to identify these individuals and co-produce mechanisms to engage, empower and ultimately emancipate these individuals to become activated in living with their conditions and in their interactions with the health system and community. This step-by-step process focuses on key issues related to the design and role of digital services in mitigating the effects of the health service inequity and avoiding the creation of an e-health divide amongst users when advocating digital behaviour change initiatives. This paper presents a matrix framework providing a scaffold across three inter-related levels of the individual; the provider, and the health and care system. The matrix framework supports examination of and reflection on the design and role of digital technologies in conjunction with pre-existing motivational instruments. This matrix framework is illustrated with examples from practice. Conclusion: It is anticipated that the matrix framework will evolve and can be used to map and reflect on approaches and practices aiming to enrich and stimulate co-production activities supported by digital technology focused on enhancing people-centred health services for the marginalised

Dataset 1.tar

Zipped; raw ABI sequence data files