MiR-10 Represses HoxB1a and HoxB3a in Zebrafish

BACKGROUND: The Hox genes are involved in patterning the anterior-posterior axis. In addition to the protein coding Hox genes, the miR-10, miR-196 and miR-615 families of microRNA genes are conserved within the vertebrate Hox clusters. The members of the miR-10 family are located at positions associated with Hox-4 paralogues. No function is yet known for this microRNA family but the genomic positions of its members suggest a role in anterior-posterior patterning. METHODOLOGY/PRINCIPAL FINDINGS: Using sensor constructs, overexpression and morpholino knockdown, we show in Zebrafish that miR-10 targets HoxB1a and HoxB3a and synergizes with HoxB4 in the repression of these target genes. Overexpression of miR-10 also induces specific phenotypes related to the loss of function of these targets. HoxB1a and HoxB3a have a dominant hindbrain expression domain anterior to that of miR-10 but overlap in a weaker expression domain in the spinal cord. In this latter domain, miR-10 knockdown results in upregulation of the target genes. In the case of a HoxB3a splice variant that includes miR-10c within its primary transcript, we show that the microRNA acts in an autoregulatory fashion. CONCLUSIONS/SIGNIFICANCE: We find that miR-10 acts to repress HoxB1a and HoxB3a within the spinal cord and show that this repression works cooperatively with HoxB4. As with the previously described interactions between miR-196 and HoxA7 and Hox-8 paralogues, the target genes are located in close proximity to the microRNA. We present a model in which we postulate a link between the clustering of Hox genes and post-transcriptional gene regulation. We speculate that the high density of transcription units and enhancers within the Hox clusters places constraints on the precision of the transcriptional control that can be achieved within these clusters and requires the involvement of post-transcriptional gene silencing to define functional domains of genes appropriately

The take up of business support by minority ethnic enterprises: the experience of South Asian businesses in England

This research contributes to a greater understanding of minority ethnic business (MEB) needs and practices and helps identify the support needs of minority ethnic firms in relation to existing support provision. The aims are, therefore, to examine the take-up of support by minority ethnic enterprises focusing mainly on the South Asian community with some representation from the African-Caribbean and Korean communities. Fifty minority ethnic businesses across South West London were contacted and semi-structured interviews took place with the owner/owner managers. The findings suggest that policy makers need to appreciate the diversity of MEBs and policies aimed at these businesses should reflect that diversity

Large format heterodyne arrays for observing far-infrared lines with SOFIA

In the wavelength regime between 60 and 300 microns there are a number of atomic and molecular emission lines that are key diagnostic probes of the interstellar medium. These include transitions of [CII], [NII], [OI], HD, H_2D^+, OH, CO, and H_2O, some of which are among the brightest global and local far-infrared lines in the Galaxy. In Giant Molecular Clouds (GMCs), evolved star envelopes, and planetary nebulae, these emission lines can be extended over many arc minutes and possess complicated, often self absorbed, line profiles. High spectral resolution (R > 10^5) observations of these lines at sub-arcminute angular resolution are crucial to understanding the complicated interplay between the interstellar medium and the stars that form from it. This feedback is central to all theories of galactic evolution. Large format heterodyne array receivers can provide the spectral resolution and spatial coverage to probe these lines over extended regions. The advent of large format (~100 pixel) spectroscopic imaging cameras in the far-infrared (FIR) will fundamentally change the way astronomy is performed in this important wavelength regime. While the possibility of such instruments has been discussed for more than two decades, only recently have advances in mixer and local oscillator technology, device fabrication, micromachining, and digital signal processing made the construction of such instruments tractable. These technologies can be implemented to construct a sensitive, flexible, heterodyne array facility instrument for SOFIA. The instrument concept for StratoSTAR: Stratospheric Submm/THz Array Receiver includes a common user mounting, control system, IF processor, spectrometer, and cryogenic system. The cryogenic system will be designed to accept a frontend insert. The frontend insert and associated local oscillator system/relay optics would be provided by individual user groups and reflect their scientific interests. Rapid technology development in this field makes SOFIA the ideal platform to operate such a modular, continuously evolving instrument

Potato tuber pectin structure is influenced by pectin methyl esterase activity and impacts on cooked potato texture

Although cooked potato tuber texture is an important trait that influences consumer preference, a detailed understanding of tuber textural properties at the molecular level is lacking. Previous work has identified tuber pectin methyl esterase activity (PME) as a potential factor impacting on textural properties. In this study, tuber PME isoform and gene expression profiles have been determined in potato germplasm with differing textural properties as assessed using an amended wedge fracture method and a sloughing assay, revealing major differences between the potato types. Differences in pectin structure between potato types with different textural properties were revealed using monoclonal antibodies specific for different pectic epitopes. Chemical analysis of tuber pectin clearly demonstrated that, in tubers containing a higher level of total PME activity, there was a reduced degree of methylation of cell wall pectin and consistently higher peak force and work done values during the fracture of cooked tuber samples, demonstrating the link between PME activity, the degree of methylation of cell wall pectin, and cooked tuber textural properties

The Impact of miRNA Target Sites in Coding Sequences and in 3′UTRs

Animal miRNAs are a large class of small regulatory RNAs that are known to directly and negatively regulate the expression of a large fraction of all protein encoding genes. The identification and characterization of miRNA targets is thus a fundamental problem in biology. miRNAs regulate target genes by binding to 3′ untranslated regions (3′UTRs) of target mRNAs, and multiple binding sites for the same miRNA in 3′UTRs can strongly enhance the degree of regulation. Recent experiments have demonstrated that a large fraction of miRNA binding sites reside in coding sequences. Overall, miRNA binding sites in coding regions were shown to mediate smaller regulation than 3′UTR binding. However, possible interactions between target sites in coding sequences and 3′UTRs have not been studied. Using transcriptomics and proteomics data of ten miRNA mis-expression experiments as well as transcriptome-wide experimentally identified miRNA target sites, we found that mRNA and protein expression of genes containing target sites both in coding regions and 3′UTRs were in general mildly but significantly more regulated than those containing target sites in 3′UTRs only. These effects were stronger for conserved target sites of length 7–8 nt in coding regions compared to non-conserved sites. Combined with our other finding that miRNA target sites in coding regions are under negative selection, our results shed light on the functional importance of miRNA targeting in coding regions

Understanding how immigrant entrepreneurs view business opportunity formation through ethnicity

Given that international research is now consistently showing higher rates of entrepreneurial activity from immigrants above native people, research regarding our understanding of how immigrant entrepreneurs view business opportunity formation remains underdeveloped. Based upon a review of the literature, this chapter examines how ethnicity relates to business opportunity formation through constant interactions. It also introduces the Visual Mixed Embeddedness Framework as an empirical lens for understanding the differences in the business opportunity formation process models between immigrant and native entrepreneurs. By explaining how factors and traits from both home and host countries impact upon the immigrant entrepreneurial business activity process, the framework clearly identifies how the concept of ethnicity influences immigrant entrepreneurial opportunity formation activities in different ways. The framework contributes to existing knowledge by offering a novel method for examining the influence on business opportunity formation of ethnicity, the role of home and host countries and variations between immigrant and native entrepreneurs

Ethnic entrepreneurs and online home-based businesses: an exploratory study

This exploratory, qualitative study considers how online home-based businesses offer opportunities for ethnic entrepreneurs to ‘break out’ of traditional highly competitive and low margin sectors. Previous studies have found a positive association between ethnic minorities’ high levels of entrepreneurship and home computer use in ethnic groups. Despite these associations, previous studies have overlooked the particular opportunities offered by home-based online businesses to ethnic entrepreneurs. The study adopts mixed embeddedness as a theoretical lens to guide interviews with 22 ethnic entrepreneurs who have started online home-based businesses in the UK. We find online home-based businesses offer ethnic entrepreneurs novel opportunities to draw on their ethnic advantages and address the constraints they face. The unique affordances of this type of business allow entrepreneurs to develop the necessary IT skills by self-learning and experimentation and to sub-contract more difficult or time consuming aspects to others. The findings also show that, consistent with the theory of mixed embeddedness, whilst the entrepreneurs are influenced by social, economic and institutional forces, online businesses allow them to exert their own agency and provide opportunities to uniquely shape these forces