Variation in histone configurations correlates with gene expression across nine inbred strains of mice.

The diversity outbred (DO) mice and their inbred founders are widely used models of human disease. However, although the genetic diversity of these mice has been well documented, their epigenetic diversity has not. Epigenetic modifications, such as histone modifications and DNA methylation, are important regulators of gene expression, and as such are a critical mechanistic link between genotype and phenotype. Therefore, creating a map of epigenetic modifications in the DO mice and their founders is an important step toward understanding mechanisms of gene regulation and the link to disease in this widely used resource. To this end, we performed a strain survey of epigenetic modifications in hepatocytes of the DO founders. We surveyed four histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac), and DNA methylation. We used ChromHMM to identify 14 chromatin states, each of which represented a distinct combination of the four histone modifications. We found that the epigenetic landscape was highly variable across the DO founders and was associated with variation in gene expression across strains. We found that epigenetic state imputed into a population of DO mice recapitulated the association with gene expression seen in the founders suggesting that both histone modifications and DNA methylation are highly heritable mechanisms of gene expression regulation. We illustrate how DO gene expression can be aligned with inbred epigenetic states to identify putative cis-regulatory regions. Finally, we provide a data resource that documents strain-specific variation in chromatin state and DNA methylation in hepatocytes across nine widely used strains of laboratory mice

Onset of deglacial warming in West Antarctica driven by local orbital forcing

The cause of warming in the Southern Hemisphere during the most recent deglaciation remains a matter of debate[superscript 1,2]. Hypotheses for a Northern Hemisphere trigger, through oceanic redistributions of heat, are based in part on the abrupt onset of warming seen in East Antarctic ice cores and dated to 18,000 years ago, which is several thousand years after high-latitude Northern Hemisphere summer insolation intensity began increasing from its minimum, approximately 24,000 years ago[superscript 3,4]. An alternative explanation is that local solar insolation changes cause the Southern Hemisphere to warm independently[superscript 2,5]. Here we present results from a new, annually resolved ice-core record from West Antarctica that reconciles these two views. The records show that 18,000 years ago snow accumulation in West Antarctica began increasing, coincident with increasing carbon dioxide concentrations, warming in East Antarctica and cooling in the Northern Hemisphere[superscript 6] associated with an abrupt decrease in Atlantic meridional overturning circulation[superscript 7]. However, significant warming in West Antarctica began at least 2,000 years earlier. Circum-Antarctic sea-ice decline, driven by increasing local insolation, is the likely cause of this warming. The marine-influenced West Antarctic records suggest a more active role for the Southern Ocean in the onset of deglaciation than is inferred from ice cores in the East Antarctic interior, which are largely isolated from sea-ice changes.Keywords: Last glacial period, Carbon Dioxide, High resolution, Chronology, Ice core, Circulation, Abrupt climate change, Atmospheric Co2, Greenland, Polar ic

Precise interpolar phasing of abrupt climate change during the last ice age

The last glacial period exhibited abrupt Dansgaard–Oeschger climatic oscillations, evidence of which is preserved in a variety of Northern Hemisphere palaeoclimate archives¹. Ice cores show that Antarctica cooled during the warm phases of the Greenland Dansgaard–Oeschger cycle and vice versa[superscript 2,3], suggesting an interhemispheric redistribution of heat through a mechanism called the bipolar seesaw[superscript 4–6]. Variations in the Atlantic meridional overturning circulation (AMOC) strength are thought to have been important, but much uncertainty remains regarding the dynamics and trigger of these abrupt events[superscript 7–9]. Key information is contained in the relative phasing of hemispheric climate variations, yet the large, poorly constrained difference between gas age and ice age and the relatively low resolution of methane records from Antarctic ice cores have so far precluded methane-based synchronization at the required sub-centennial precision[superscript 2,3,10]. Here we use a recently drilled high-accumulation Antarctic ice core to show that, on average, abrupt Greenland warming leads the corresponding Antarctic cooling onset by 218 ± 92 years (2σ) for Dansgaard–Oeschger events, including the Bølling event; Greenland cooling leads the corresponding onset of Antarctic warming by 208 ± 96 years. Our results demonstrate a north-to-south directionality of the abrupt climatic signal, which is propagated to the Southern Hemisphere high latitudes by oceanic rather than atmospheric processes. The similar interpolar phasing of warming and cooling transitions suggests that the transfer time of the climatic signal is independent of the AMOC background state. Our findings confirm a central role for ocean circulation in the bipolar seesaw and provide clear criteria for assessing hypotheses and model simulations of Dansgaard–Oeschger dynamics

Culture, society and musical learning

In the limited space I have here, I focus on the way in which long-standing beliefs and assumptions about music influence the way in which music is taught. I address the ways in which such assumptions have come to be seen as self-evident and suggest strategies for addressing some of the negative impact this has on music teaching and learning

Musical knowledge, critical consciousness and critical thinking

The concept of critical thinking is understood in a number of ways. In some definitions it is close to the idea of metacognition - ‘thinking about thinking’ - whilst in others it describes a process of ‘logical thinking’ involving the gathering, assimilation and analysis of evidence from which emerges a ‘reasoned’ conclusion. In his book Democracy and Music Education (2005) Paul Woodford suggests that although critical thinking is supposed to ‘develop independence of mind’ it is almost always equated in curriculum documents ‘with the application and development of abstract thinking skills and abilities divorced from social, moral, ethical or political considerations’ and that ‘Few music teachers realize that this separation of mind and matter is a perversion of what Dewey, one of the fathers of the contemporary critical thinking movement, intended’ (Woodford 2005: 95). In this chapter I will explore critical thinking as part of the framework of critical (social) theory and examine how, as I have written elsewhere, ‘properly embedded, critical thinking and understanding enables pupils to make connections between their musical learning in school and their lived reality, and thus empower them as learners’(Spruce 2009: 36). Critical thinking is here conceptualized as a key element in the development of a more socially just society in which all are enabled to fully participate. I will argue however that in order to create the conditions within which critical thinking can flourish, we need to examine the ways in which knowledge is conceptualized and understood and how knowledge, particularly in school, is positioned in relation to the ‘knower’ or ‘learner’. I will suggest that such a reconceptualization will inevitably present challenges to some pedagogical approaches. I begin the chapter by exploring the philosophical underpinning of some commonly-held conceptions of the nature of knowledge and the relationship of the knower to knowledge; noting through examples from music education the impact these relationships can have on young people’s experiences of music in school. Drawing on the ideas of Paulo Freire (1970; 1974) I will then explore how through a process of ‘conscientization’ leading to critical consciousness, and supported by a critical pedagogy, critical thinking might be nurtured and ‘independence of mind’ developed within the music classroom. At various points in the chapter I will exemplify the points being made with brief examples or more worked out ‘case studies’ from music classroom practice

Integrations: setting the scene

Making Music in the Primary School is an essential guide for all student and practising primary school teachers, instrumental teachers and community musicians involved in music with children. It explores teaching and learning music with the whole class and provides a framework for successful musical experiences with large groups of children.Illustrated throughout with carefully designed activities to try out in the classroom, the guidance in this book will help you support and develop children's musical experience, whatever your musical or teaching background.Underpinned by theory and proven good practice, the book is structured around the four key principles that underpin effective music teaching and experience:Integration ' how can we join up children's musical experience?Creativity ' how can we support children's musical exploration?Access and Inclusion ' how can we provide a relevant experience for every child?Collaboration ' how might we work together to achieve these aims

Access and inclusion: setting the scene

About the book: Making Music in the Primary School is an essential guide for all student and practising primary school teachers, instrumental teachers and community musicians involved in music with children. It explores teaching and learning music with the whole class and provides a framework for successful musical experiences with large groups of children.Illustrated throughout with carefully designed activities to try out in the classroom, the guidance in this book will help you support and develop children's musical experience, whatever your musical or teaching background.Underpinned by theory and proven good practice, the book is structured around the four key principles that underpin effective music teaching and experience:Integration ' how can we join up children's musical experience?Creativity ' how can we support children's musical exploration?Access and Inclusion ' how can we provide a relevant experience for every child?Collaboration ' how might we work together to achieve these aims

Listening and appraising and the ideology of aesthetic listening

In this chapter we explore the assumptions and beliefs that underpin aesthetic listening. We then go on to explore the impact of aesthetic listening on music teaching and learning through analysing three hypothical examples of the way in which listening and appraising are taught in the music classroom. Following this, issues associated with the personal construction of musical meaning and appraisal responses other than verbal and written ones are considered. Finally, we suggest ways in which listening and appraising can be taught through integration with composing and performing activities