The Doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1

The mechanisms that determine whether a neural progenitor cell (NPC) re-enters the cell cycle or exits and differentiates are pivotal for generating cells in correct numbers and diverse types, and hence dictate proper brain development. Combining gain-of-function and loss-of-function approaches in an embryonic stem cell-derived cortical differentiation model, we report that Dmrta2 plays an important role in maintaining NPCs in the cell cycle. Temporally controlled expression of transgenic Dmrta2 in NPCs suppresses differentiation without affecting their neurogenic competence. In contrast, Dmrta2 knockout accelerates the cell cycle exit and differentiation into post-mitotic neurons of NPCs derived from embryonic stem cells and in Emx1-cre conditional mutant mice. Dmrta2 function was linked to the regulation of Hes1 and other proneural genes as demonstrated by genome wide RNAseq and direct binding of Dmrta2 to the Hes1 genomic locus. Moreover, transient Hes1 expression rescues precocious neurogenesis in Dmrta2 knockout NPCs. Our study therefore establishes a novel link between Dmrta2 modulation of Hes1 expression and the maintenance of NPCs during cortical development.

Intercomparison of ground-based ozone and NO2 measurements during the MANTRA 2004 campaign

The MANTRA (Middle Atmosphere Nitrogen TRend Assessment) 2004 campaign took place in Vanscoy, Saskatchewan, Canada (52° N, 107° W) from 3 August to 15 September, 2004. In support of the main balloon launch, a suite of five zenith-sky and direct-Sun-viewing UV-visible ground-based spectrometers was deployed, primarily measuring ozone and NO2 total columns. Three Fourier transform spectrometers (FTSs) that were part of the balloon payload also performed ground-based measurements of several species, including ozone. Ground-based measurements of ozone and NO2 differential slant column densities from the zenith-viewing UV-visible instruments are presented herein. They are found to partially agree within NDACC (Network for the Detection of Atmospheric Composition Change) standards for instruments certified for process studies and satellite validation. Vertical column densities of ozone from the zenith-sky UV-visible instruments, the FTSs, a Brewer spectrophotometer, and ozonesondes are compared, and found to agree within the combined error estimates of the instruments (15%). NO2 vertical column densities from two of the UV-visible instruments are compared, and are also found to agree within combined error (15%)

Controlled release of Dextrin-conjugated growth factors to support growth and differentation of neural stem cells

An essential aspect of stem cell in vitro culture and in vivo therapy is achieving sustained levels of growth factors to support stem cell survival and expansion, while maintaining their multipotency and differentiation potential. This study investigated the ability of dextrin (~74,000 g/mol; 27.8 mol% succinoylation) conjugated to epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF; or FGF-2) (3.9 and 6.7% w/w protein loading, respectively) to support the expansion and differentiation of stem cells in vitro via sustained, controllable growth factor release. Supplementation of mouse neural stem cells (mNSCs) with dextrin-growth factor conjugates led to greater and prolonged proliferation compared to unbound EGF/bFGF controls, with no detectable apoptosis after 7 days of treatment. Immunocytochemical detection of neural precursor (nestin) and differentiation (Olig2, MAP2, GFAP) markers verified that controlled release of dextrin-conjugated growth factors preserves stem cell properties of mNSCs for up to 7 days. These results show the potential of dextrin-growth factor conjugates for localized delivery of bioactive therapeutic agents to support stem cell expansion and differentiation, and as an adjunct to direct neuronal repair

The shape of equality: discourses around the Section 28 repeal in Scotland

This article focuses on conceptualizations of equality in the discourses deployed in the campaign to repeal Section 28 in Scotland. I use the parliamentary debates and two newspapers: the Daily Record, which supported the campaign to Keep the Clause, and The Guardian, which supported repeal, to exemplify the different discursive articulations around equality and citizenship. I suggest that the Scottish example provides further evidence of the ways in which liberalism naturalizes heterosexuality as the standard for citizenship and thus bequeaths a hierarchy of 'equality' and citizenship in the realm of sexuality, wherein lesbian and gay citizenship is either rendered invalid or characterized as 'special rights'. However, within the narrow confines of the parliamentary debates, more expansive and differentiated notions of citizenship and equality are evident. Whilst I conclude that the 'shape' of equality achieved through the repeal has been moulded to support institutionalized heterosexuality - with Section 28 replaced by statutory guidelines on sex education which advocate marriage - I also suggest equality is contested, both through the recognition of transformations in heterosexual family forms and the appeal to non-discrimination as a democratic principle. It is possible, therefore, that current destabilizations of the heterosexual social order simultaneously destabilize the precepts of liberal democracy

Relational happiness through recognition and redistribution:Emotion and inequality

This article develops a model of relational happiness that challenges popular individualized definitions and emphasizes how it can enhance the sociological analysis of inequality. Many studies of happiness suggest that social inequalities are closely associated with distributions of happiness at the national level, but happiness research continues to favour individual-level analyses. Limited attention has been given to the intersubjective aspects of happiness and the correlations between it and higher social equality. Conversely, key theoretical debates about inequalities, such as Axel Honneth and Nancy Fraser\u27s exchanges, have only indirectly touched on happiness. A relational approach to happiness is not new, but what this article offers is a new combination of a relational understanding of happiness as an intersubjectively, culturally experienced complex of emotions with discussions about recognition of marginalized groups and redistribution of material resources. This combined approach can further debates about understanding and remedying social inequalities. It argues that theories and measurements of happiness must consider how it can be achieved collectively through working at mutual respect as well as greater material equality

A 3D ex vivo mandible slice system for longitudinal culturing of transplanted dental pulp progenitor cells

Harnessing mesenchymal stem cells for tissue repair underpins regenerative medicine. However, how the 3D tissue matrix maintains such cells in a quiescent state whilst at the same time primed to respond to tissue damage remains relatively unknown. Developing more physiologically relevant 3D models would allow us to better understand the matrix drivers and influence on cell-lineage differentiation in situ. In this study, we have developed an ex vivo organotypic rat mandible slice model; a technically defined platform for the culture and characterization of dental pulp progenitor cells expressing GFP driven by the β-actin promoter (cGFP DPPCs). Using confocal microscopy we have characterized how the native environment influences the progenitor cells transplanted into the dental pulp. Injected cGFP-DPPCs were highly viable and furthermore differentially proliferated in unique regions of the mandible slice; in the dentine region, cGFP-DPPCs showed a columnar morphology indicative of expansion and lineage differentiation. Hence, we demonstrated the systematic capacity for establishing a dental pulp cell-micro-community, phenotypically modified in the tooth (the “biology”); and at the same time addressed technical challenges enabling the mandible slice to be accessible on platforms for high-content imaging (the biology in a “multiplex” format)