Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing

Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2), plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossing-over in homologous recombination and in meiotic sex chromosome inactivation (MSCI). Disruption of the Setx gene caused persistence of DNA double-strand breaks, a defect in disassembly of Rad51 filaments, accumulation of DNA:RNA hybrids (R-loops), and ultimately a failure of crossing-over. Senataxin localised to the XY body in a Brca1-dependent manner, and in its absence there was incomplete localisation of DNA damage response proteins to the XY chromosomes and ATR was retained on the axial elements of these chromosomes, failing to diffuse out into chromatin. Furthermore persistence of RNA polymerase II activity, altered ubH2A distribution, and abnormal XY-linked gene expression in Setx⁻/⁻ revealed an essential role for senataxin in MSCI. These data support key roles for senataxin in coordinating meiotic crossing-over with transcription and in gene silencing to protect the integrity of the genome.

Functional role for senataxin, defective in ataxia oculomotor apraxia type 2, in transcriptional regulation

Ataxia oculomotor apraxia type 2 (AOA2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. The gene mutated in AOA2, SETX, encodes senataxin, a putative DNA/RNA helicase which shares high homology to the yeast Sen1p protein and has been shown to play a role in the response to oxidative stress. To investigate further the function of senataxin, we identified novel senataxin-interacting proteins, the majority of which are involved in transcription and RNA processing, including RNA polymerase II. Binding of RNA polymerase II to candidate genes was significantly reduced in senataxin deficient cells and this was accompanied by decreased transcription of these genes, suggesting a role for senataxin in the regulation/modulation of transcription. RNA polymerase II-dependent transcription termination was defective in cells depleted of senataxin in keeping with the observed interaction of senataxin with poly(A) binding proteins 1 and 2. Splicing efficiency of specific mRNAs and alternate splice-site selection of both endogenous genes and artificial minigenes were altered in senataxin depleted cells. These data suggest that senataxin, similar to its yeast homolog Sen1p, plays a role in coordinating transcriptional events, in addition to its role in DNA repair.

Drawing and writing on the screen

This chapter focuses on the physicality of the iPad as an object, and how that physicality affects the interactions children have with the device generally, and the apps specifically. Thinking about the physicality of the iPad is important because the materials, size, weight and appearance make the iPad quite unlike most other toys and equipment in the kindergarten space. Most strikingly, this physicality does not ‘represent’ the virtual vast dimensions of the iPad brought about through the diverse functions and contents of the apps contained in it. While the iPad is small enough and functional enough to be easily handled and operated even by young children, it is capable of performing highly complex, highly technological tasks that take it beyond its diminutive dimensions. This virtual-actual contrast is interesting to consider in relation to the other resources more commonly found in a kindergarten space. While objects such as toys, bricks, building materials often do prompt the child to imagine and invent beyond the physical boundaries of the toy, they not have the same types of virtual-actual contrasts of a digital device such as the iPad. How then, might children be drawn to the iPad because of its physical, technological and virtual difference? Particularly, how might this virtual-actual difference impact on the physical skills associated with writing and drawing: skills usually learnt through the use of a pencil and paper? While the research project did not set out to compare how digital and paper-based resources affect writing and drawing skills there was great interest to see how young children negotiated drawing and writing on the shiny glass surface of the iPad.

Visual arts learning with iPads

In this chapter Knight & Dooley discuss arts learning and issues of educational authenticity via children’s engagement with iPads (O’Mara & Laidlaw 2011; Shifflet, Toledo & Mattoon 2012). The chapter begins by considering common perceptions about art and how these popular beliefs and conditions affect and influence how children’s art is defined and valorized. The art produced by children using iPads is then discussed through key observations and reflections, and the chapter concludes with some recommendations when selecting apps for making art.

Troubling dissemination : experimentations with the salon as conference event

Salons became popular in Europe in 17th Century as sites of philosophic and literary conversation. A group of female academics interested in Deleuzian theories experimented with the salon to challenge presentation and dissemination norms that hierarchize and centralize the human. For Deleuze and Guattari (1987), assemblages are shifting and decentering, so how might assemblages of chairs, tables, bodies, lights, space, help to trouble thinking about the methodological conventions around academic disseminations? The authors discuss the salon as a critical-cultural site: Cumming presents Deleuze and play-dough, an exploration of how the playful dissemination format of the salon prompted a re-reading of a methodological vignette from earlier research. Knight, an arts-based researcher, uses video art as a creative methodology to examine conceptualizations of rhizomes and assemblages at the salon as a dissemination site. The authors conclude that the salon, as a critical, cultural site disrupts hierarchized ways of approaching and presenting research.

Drawing out critical thinking : testing the methodological value of drawing collaboratively

Early childhood research has long established that drawing is a central, and important activity for young children. Less common are investigations into the drawing activity of adults involved in early childhood. A team of adult early childhood researchers, with differing exposures and familiarities with drawing, experimented with intergenerational collaborative drawing with colleagues, students, family members and others, to explore the effectiveness of drawing as a research process and as an arts-based methodology. This testing prompted critical thinking into how drawing might facilitate research that involves young children, to operate in more communicable ways, and how research-focused drawings might occur in reference to a research project.

Geminin and Brahma act antagonistically to regulate EGFR–Ras–MAPK signaling in Drosophila

Geminin was identified in Xenopus as a dual function protein involved in the regulation of DNA replication and neural differentiation. In Xenopus, Geminin acts to antagonize the Brahma (Brm) chromatin-remodeling protein, Brg1, during neural differentiation. Here, we investigate the interaction of Geminin with the Brm complex during Drosophila development. We demonstrate that Drosophila Geminin (Gem) interacts antagonistically with the Brm–BAP complex during wing development. Moreover, we show in vivo during wing development and biochemically that Brm acts to promote EGFR–Ras–MAPK signaling, as indicated by its effects on pERK levels, while Gem opposes this. Furthermore, gem and brm alleles modulate the wing phenotype of a Raf gain-of-function mutant and the eye phenotype of a EGFR gain-of-function mutant. Western analysis revealed that Gem over-expression in a background compromised for Brm function reduces Mek (MAPKK/Sor) protein levels, consistent with the decrease in ERK activation observed. Taken together, our results show that Gem and Brm act antagonistically to modulate the EGFR–Ras–MAPK signaling pathway, by affecting Mek levels during Drosophila development.

Community arts in early childhood

Community arts can take many forms, including murals, installations, festivals and performances. The work can be produced by artists solely, by artists working with community groups, or by community groups. Community arts can be on a grand-scale covering whole streets, parks or even towns, or small- scale, such as a mosaic in the corner of a play area. It can be extremely impacting and a permanent fixture, or fragile and small and designed to blow away in the wind. But, common to all these different forms of community arts are the criteria that community arts are made in, for and/or by, the local community.