bluuebunny/crossref_metadata_2025 huggingface dataset:
Jordan
Authors: Hamarneh Walid
Published: August 2017

This chapter discusses the development of the novel in Jordan. It first provides an overview of the beginnings of the novel as a genre in Jordan, focusing on works that tend to be filled with direct, almost sermon-like, preaching, digressions into various unrelated topics, and popular psychological analysis. It then considers the maturation of the novel in Jordan, noting how the collapse of the dominant ideologies of nationalism associated with Egypt’s Nasser and the Syrian Ba‘ath Party seems to have worked as an impetus for a new kind of novel writing in the country. It also looks at a younger generation of Jordanian authors, along with the significant leap in Jordanian novelistic production from the 1970s to the mid-1980s. Finally, it examines the emergence of the historical novel and the works of women authors.
Mauritania
Authors: Blalack J.S.
Published: August 2017

This chapter traces the origins of the novel genre in Mauritania. It first considers the cultural and historical context of the emergence of the Mauritanian novel, focusing on its link to the rise of Nouakchott as the country’s capital. It then discusses the rise of the Arabic novel and the influence of the Nahḍa movement on many Arabic-speaking Mauritanians, including Aḥmad wuld ʻAbd al-Qādir, Al-Sunnī ʻAbdāwa, and Tarba bint ʻAmmār. It also examines the Francophone novel. The chapter concludes by reflecting on the future of the Mauritanian novel, noting that Mauritanian literature suffers from marginalization in the Arab world and neglect on the part of academics and critics.
Saudi Arabia
Authors: al-Ghadeer Moneera
Published: August 2017

This chapter discusses the development of the novel genre in Saudi Arabia. The early novels in Saudi Arabia were not considered a form of entertainment and had limited readership because, until recently, poetry was the dominant genre. The development of the novel was slow in the period 1930–1959, and novels tended to focus on cultural and social reform, varying from skepticism about external influences to a more balanced staging of dialogue with the Other. This chapter examines the Saudi novel’s movement toward new modes of innovation and modernism during the period 1959–1970, and 1980–2012, women’s literature and the depiction of women in the Saudi novel, and the contribution of women writers in the efflorescence of the genre. It also considers novels that challenge ethos of concealment, leading to negative aesthetics in the new millennium.
Building a Broad View of Technology in Music Teacher Education
Authors: Partti Heidi
Published: August 2017

In addition to innovative policy schemes, program visions, and curricular changes, the transformation of the school classroom necessitates also the development of teacher education. Inspired by the Core Perspective chapters in this section of the handbook, this chapter discusses issues related to the use of technology in supporting the cultivation of creative and collaborative skills in music teaching, particularly from the viewpoint of music teacher education. The chapter argues that there is a gap between the potential that technology could provide for music teaching and learning processes and the cultivation of this potential in schools. To bridge this gap, a holistic approach to technology and its use in music education is required. According to this approach, technology is viewed as a powerful way to facilitate more possibilities to participate in different musical practices and to use musical imagination.
Loaded Questions for an Emerging World of Music Education Technology
Authors: Bush John-Morgan
Published: August 2017

In order to provide the best possible education for our students, it is imperative to consider the all-too-human reactions to ICT (information and communication technology) as experienced by all stakeholders in the music learning environment. We must carefully evaluate several loaded questions to fully investigate the impact that ICT can have in our classrooms. This Further Perspective questions the various ways classroom technology can destabilize the long-standing model of apprenticeship to mastery in instrumental music as well as how professional pressure points motivate or deter the use of ICT in the music classroom. In addition, this chapter explores how the unchecked use of ICT applications can destabilize the social structures within musical learning communities.
Interest-Driven Music Education
Authors: Peppler Kylie
Published: August 2017

This chapter examines how music education can benefit from the use of new electronic tools and materials for music making that allow learners to combine their interests and prior understandings toward deepening their engagement in music. This chapter puts forward a series of new examples that are transforming tradition music education, including rhythmic video games, like Rock Band, which can help bridge the large chasm that exists between youths’ music culture and traditional music education. In addition, inexpensive recording hardware and software such as Audacity and GarageBand have provided youth with opportunities to compose and perform as only professional musicians could in the past, uniquely shifting the professional recording and composition landscape. Other prominent examples include software like Impromptu, which successfully engages youth in music composition and analysis by enabling users to create and remix tunes using virtual blocks that contain portions of melodies and/or rhythmic patterns that allow one to understand music theory and composition at much younger ages. Collectively this work heralds a shift in twenty-first-century music education, which has the potential for engaging greater numbers of young learners in authentic music making and performance.
Technology in Music Education in England and across Europe
Authors: Gall Marina
Published: August 2017

In this chapter, adopting an autobiographical perspective, I reflect upon the use of music technology within English school classrooms during the last 50 years. The chapter illustrates that this has become so important—particularly for creative work—that formal music technology examination syllabi for older students now exist alongside courses that focus on “traditional” music skills. The chapter also discusses the less positive position of information communications technology within the music curricula for primary school children and secondary students aged 11–14, and offers thoughts on the future of music technology within the English education system. As a backdrop to the discussion the chapter presents a short reflection on music technological developments in society during the twentieth and twenty-first centuries. The chapter also includes the perspectives of music educators from a wide range of European countries, during the period 2008–2011, on the position of music technology within their own educational contexts.
On Becoming Musical
Authors: Greher Gena
Published: August 2017

This chapter examines the role of both high- and low-tech solutions, when using music technology as a form of reflective practice in working with special needs populations. Music teachers often are given little coursework in working with at-risk and special needs students. It is little wonder that music teacher attitudes are often negative regarding the inclusion of these students in music activities, whether it’s in a general music class or ensembles. Rather than marginalizing these students, music technology can be adapted to allow even the most severely impacted student a means to music participation in school settings. Providing music education students with context-specific field experiences working with a variety of special needs populations can help students realize the musical potential of all students.
Technology and Music Collaboration for People with Significant Disabilities
Authors: DeVito Donald
Published: August 2017

This chapter centers on the potential of technology to greatly transform the way people with disabilities experience and express themselves through music. A variety of methods for developing the untapped potential of music participants with complex needs in the modern music classroom are discussed. Widely available technology, such as Skype, Google Hangout, and simple online communication technology, create real and enduring international connections and interactions in music education for all learners. The definitions of music and musicianship are discussed, considering twenty-first-century issues and trends in the inclusive classroom. How we define who is a musician and who is considered to have the prerequisite music skills and expertise to be referred to as a performer will increasingly change, or in fact become irrelevant, with the advent of personal music technology. The result will be music opportunities for all special needs populations around the world.
Possibilities for Inclusion with Music Technologies
Authors: Vanderlinde Deborah
Published: August 2017

Universal design for learning is a commitment to differentiation on every level, presenting and engaging with content in varied and flexible ways. That is, teachers might provide multiple ways for students to engage with content and to express what they know with multiple avenues for applying and assessing understanding (aurally, orally, with singing, verbally, visually, enactively, kinesthetically, with iconic representation, with manipulatives and assistive technologies). These principles are best practices for all teaching, but essential for learners with exceptionalities. Mobile technologies have much to offer as a form of assistive technology for learners with exceptionalities. This Further Perspective explores these possibilities.
Technology and Invisibility in Music Teacher Education
Authors: Greher Gena
Published: August 2017

The purpose of technology in the music teacher education curriculum is examined in this chapter. While it is easy to view technology as an efficient content delivery system, that perspective does little to support pedagogical transformation or twenty-first-century skill acquisition. State teacher certification requirements mired in twentieth-century practices have done little to encourage a rethinking of the music teacher education curriculum to include a more expansive and constructionist view of the role technology can play in music education. Those creating the curricular guidelines for higher education in music are perhaps conflating the pervasive existence of the technological tools available to our students with the existence of a sound pedagogy for working with these tools. By providing a pedagogical approach based on creating with technology, we can begin to bridge the disconnect between music education practice and the multiple ways that our students understand music on their own outside school.
Why Isn’t Music Education in the United States More Twenty-First-Century PC?
Authors: Freedman Barbara
Published: August 2017

This chapter addresses three themes in the Core Perspectives. First, it argues that preservice teachers should be trained in music technology and technology pedagogy as one would train preservice teachers on brass, woodwinds, percussion, or piano. Second, she suggests that in-service teachers are the experts in their classrooms, regardless of their preexisting competence with any individual subdomain—brass, percussion, or, in this case, technology. Just as experienced band teachers have no problem asking their advanced trumpet player students to help the beginning trumpet player students, teachers can similarly capitalize on students with technological competence. Third, the chapter argues that the U.S. music education system, K-university, is implicitly skewed toward middle to upper economic class culture and, by nature, disinherits those who seek to engage in other musical cultures. Technology, she suggests, is an excellent way to better meet the needs of all students.
Selected to Kill in His Name
Authors: Sela Yael , Barbaro Nicole
Published: August 2017

Religion motivates, exacerbates, and even justifies violence. This chapter argues that religious beliefs regarding violence—particularly those of monotheistic, Abrahamic faiths—are shaped by evolved psychological mechanisms. Further, it argues that religiously motivated violence is most likely to occur in evolutionarily relevant contexts. Guided by sexual selection theory and parental-investment theory, it first provides an overview of human sexual selection from an evolutionary perspective. It discusses how and why an evolutionary perspective—and principles of sexual selection and parental investment in particular—may provide a richer understanding of religiously motivated violence. Next follows an overview of research addressing several types of religiously motivated violence such as mate guarding and controlling behaviors, wife beating and uxoricide, honor killing, child abuse and filicide, male and female genital mutilation, war, and terrorism. Finally, it highlights the parallels between religiously motivated violence and evolved psychological mechanisms for violence, concluding with suggestions for future research.
Gender and Slavery
Authors: Glazebrook Allison
Published: August 2017

This chapter investigates the relation between gender and slavery among the Greeks and Romans. It considers the gendered division of labour for slaves with a special emphasis on female slaves and female masters in the domestic context. Important topics covered include sexual violence against slaves, manumission, and prostitutes as slaves. It argues that female slaves were most common in domestic contexts and the sex and entertainment industry. Both contexts, however, meant that female slaves were open to sexual abuse, but close contact with the free might also benefit female slaves by leading to their manumission. Slaves frequently appear outside ancient constructions of gender, officially denied socio-political status as husbands, wives, fathers, and mothers, and free from behavioural expectations like male courage and female virtue; but this lack of a gendered identity was likely another element of their oppression.
Laying the Foundations: 1910–1948
Authors: Campbell Ted A. , MacDonald Gary B.
Published: August 2017

This chapter details the evolution of the constituent bodies of the World Council of Churches in the period between 1910 and the Council’s formal organization in 1948. It shows how these constitutive components (the International Missionary Council, the Faith and Order movement, and the Life and Work movement) grew originally from Protestant postmillennial optimism at the start of the twentieth century and evolved in the wake of the First World War, the rise of the Soviet state, the global economic depression of the 1930s, the rise of German National Socialism, the Second World War, and the destruction that the war brought about. All of these factors made ecumenical engagement utterly urgent in the eyes of the leaders of the ecumenical movement. The chapter also shows how Eastern Orthodox churches and representatives of the Catholic Church, even prior to the Second Vatican Council, became engaged at varying levels with ecumenical work.
Intense Activity: 1965–1990
Authors: Gassmann Günther
Published: August 2017

This chapter explains that 1965–1990 was a highly intensive period of ecumenical action and reflection. A new and very active partner had entered the ecumenical scene, namely the Roman Catholic Church, following the Second Vatican Council. There were also significant new developments in social action and theological reflection and a number of outstanding events. A radical, holistic vision of mission emerged and prompted critical reaction from the evangelical Lausanne Movement. Ecumenical theological studies under the auspices of Faith and Order on common faith, sacraments, and unity drew much attention, especially in relation to the most widely distributed and discussed ecumenical document thus far: Baptism, Eucharist and Ministry (BEM) of 1982. New perspectives on the community of women and men in church and society were also developed.
The Ecclesiastical Polity
Authors: Shagan Ethan
Published: August 2017

The ecclesiastical polity, and the laws that governed it, were at the heart of post-Reformation England’s constitution. Yet there was no consensus about where the ecclesiastical polity was located, who made its laws, or how those laws should be enforced; the same theological compromises that helped preserve the peace of the Church rendered religious law incoherent. Famously, Richard Hooker attempted to resolve this incoherence in his Of the Lawes of Ecclesiastical Politie, but he failed to do so, as did all subsequent early modern attempts. The result was that, well into the nineteenth century, the fundamental ambiguity of the ecclesiastical polity—was it an object of human discretion, or was it an unfolding of God’s revealed plan?—challenged and undermined the precocious rationality of the first modern state.
The Changing Persona of the Justices and their Quarter Sessions
Authors: Landau Norma
Published: August 2017

The standard portrait of the justices of the peace of early modern England is that of gentry, landed provincials, conducting their counties’ local government and so personifying ‘self-government at the king’s command.’ This essay disputes that depiction. First, it argues that it was not until relatively late in the early modern era that local gentry determined the persona of the county bench. Second, it argues that it was not until the later seventeenth century that the early modern state sufficiently differentiated its functions so as to create ‘local government.’ In so doing, it created a sphere of government fit for provincial rulers.
Law and the Evidentiary Environment
Authors: Shapiro Barbara
Published: August 2017

This essays explores several epistemological related elements in the early modern English jury trial environment. Witnessing, credibility, testimony, doubt, suspicion, equivocation, conscience, fact, and oaths are frequent topics in law and literature studies. In one way or another, all of them raise questions of truth-telling, fact-finding, and epistemology. This environment included oath taking, the credibility of oath and non oath takers, the rhetorical origins of credibility criteria, casuistry, and the legal language of ‘satisfied conscience’, and the interplay between ‘truth’ and ‘mercy.’ It also discusses the consistency, tension, and/ or conflict between conceptual elements and the practices of grand jurors, jurors, and judges.
Witch Wives
Authors: Dolan Frances
Published: August 2017

While many historians of witchcraft have contrasted witch and wife, not only assuming that most accused women were unmarried but placing them at opposite ends of a gendered moral continuum, this essay explores how the witch wife depicted in early modern pamphlets and plays, standing at one of the many crossroads of law and literature, condenses and expresses concerns about what all wives want and what kinds of bargains wives would make if they could. In the witch wife, we can see the embodiment of wishes that can change the world, of fantasies that materialize. Lurking behind the extraordinary stories of demon lovers and efficacious maleficia lie very ordinary concerns about the inscrutable yet industrious interiority of women, especially wives.
Empire and Natural Law in Dryden’s Heroic Drama
Authors: Holberton Edward
Published: August 2017

Dryden’s early heroic plays find dramatic potential in early modern natural law debates about sovereignty, and explore the language of contract central to these debates. The Indian Emperour interrogates the context of Spain’s claims to empire in the new world, reflecting the historical moment of England’s growing colonial ambitions. The Conquest of Granada shows how natural law’s metaphors of contract can destabilize an empire from within, as Dryden’s hero Almanzor employs them to contest and divide. Almanzor’s claims connect to an earlier critical exchange between Davenant and Hobbes on the cultural influence of epic romance and theatre in relation to political instability. Dryden’s play, however, works to redeem romance from its association with the misinterpretation of passion and interest in Hobbes’s writing. In The Conquest of Granada, romance and theatre become part of the process of refined law-making, providing a culture of propriety and discrimination which supports the artifice of empire.
Censorship in Law and Practice in Seventeenth-Century England
Authors: Raymond Joad
Published: August 2017

Revisionist histories of censorship have contended that the state’s infrequent and essentially ad hoc interventions in print in early modern England reveal that the Whig history of censorship is a mere fiction. This chapter explores the spectrum of procedures for managing print in the period, the economic and the ideological, the typical and the exceptional, and suggests that the very arbitrariness of interventions may have been part of their effectiveness. The law combined with less formal, everyday procedures to provide a range of means of managing print that was neither the Whigs’ monolithic control nor the Revisionists’s liberal freedom.
Paradise Lost?
Authors: Brooks Christopher
Published: August 2017

This is the text of the Annual Lecture for the Centre for Mediaeval and Early Modern Law and Literature, delivered by the late Professor Christopher Brooks at the University of St Andrews 9 October 2013. The first part consists of observations arising from comparisons between Professor Brooks’s vision of legal culture between roughly 1550 and 1640 and his understanding of its relation to contemporary literature. A particularly important question in connection with this is whether or not both the great excrescence of legal culture in this period and the extensive crossover with literature were in some respects unique. The second part of the lecture examines the changing relationship between law and social and political life during the Civil War years and those after the Restoration of 1660.
John Foxe’s Book of Martyrs
Authors: Pincombe Mike , Schwart-Leeper Gavin
Published: August 2017

This chapter traces the relationship between Reformist conceptions of tragedy, tyranny, and martyrdom in John Foxe’s Acts and Monuments. First published by John Day in 1563 and revised extensively in 1570, 1576, and 1583 prior to Foxe’s death, the Book of Martyrs (as it was popularly called) provided readers with sensational representations of the suffering and piety of the Marian martyrs as part of a Reformist ecclesiastic history. This chapter argues that Foxe presents this contention as a generic issue: the tragedy of death is transformed by an apocalyptic theology into a type of sacred tragi-comedy. Through Foxe’s keen sense of the polemical and conversional power of performance, the Book of Martyrs demonstrates the interplay between Reformist apocalyptic theology and early modern spectacle.
Edmund Spenser
Authors: Heale Elizabeth
Published: August 2017

This chapter outlines some of the key features of Elizabethan Protestantism relevant for Spenser’s work and goes on to consider both their importance as themes in his poetry, and their influence on his understanding of his art and his choice of poetic forms. The ecclesiastical debates of The Shepheardes Calendar are discussed, as well as the problems of detecting a single authoritative point of view. The Faerie Queene is considered as a Protestant epic, with its themes and its form discussed in terms of contemporaneous doctrinal and political religious issues and Protestant attitudes to art. A final section considers Spenser’s move away, in his final works, from his problematic role as poet of a Protestant queen and state to a new reformed poetry of love that vests a quasi-vatic authority in the poet himself.
Philip Sidney and Mary Sidney Herbert
Authors: Perry Nandra , Stillman Robert E.
Published: August 2017

This chapter traces the interconnections among piety, politics, and poetry in the life and work of Philip Sidney and Mary Sidney-Herbert: the siblings whose partnership arguably launched the English literary Renaissance as we know it. As co-creators of The Sidney Psalter and The Countess of Pembroke’s Arcadia, Philip and Mary pioneered an aesthetic fashioned from their consciousness of the Fall. They imagine into being fictions whose scope is to move readers to lives of active virtue by inspiring them with dazzling images of ‘what may be and should be’. While the optimism of such a poetics may seem at odds with Protestant theology as it is sometimes understood, it is in fact an outgrowth of the Sidneys’ Reformed commitments. By way of engagement, especially with the ideas of Philip Melanchthon’s humanist followers, they shaped a religiously moderate, anti-confessional literary culture at odds with the strict Calvinism of the day.
Settlers in New Worlds
Authors: Hodgkins Christopher
Published: August 2017

Early modern colonial survival meant that imaginative writings about settlers in new worlds outnumbered imaginative writings by those settlers; yet new world settlers did leave literary artefacts of their interpretive communities. Writing about new worlds tended to fire the fancy, either in fantastic exploration narratives, fabulous colonial prospecti, reflective essays, or in the more outright fictions of dramatic and utopian literature, and of lyric and epic poetry. Writing in and from new worlds was often more quotidian, with nonfiction prose genres like ships’ logs, company reports, personal letters, spiritual diaries, and sermons predominating with a sprinkling of original poetry, proverb, and song. Old genres were modified, and new ones born, by necessity and invention: not only the traveller’s tale and ‘utopian’ fiction, but also the conquest story, the atrocity exposé, the settlers’ covenant, the captivity and conversion narrative, and the extended Eucharistic meditation and puritan jeremiad—and the novel.
‘Finding the Genuine Light of Nature’
Authors: Price Bronwen
Published: August 2017

This chapter explores four significant figures: Francis Bacon, Robert Boyle, Henry More and Anne Conway, each of whom represents an important and distinct aspect of the relationship between religion and science in the early modern period. It considers diverse approaches to questions such as whether matter is connected to spirit and the extent to which the workings and causes of physical phenomena are separate from those of metaphysical design and purpose, thus demonstrating the ways in which theological and scientific concerns are frequently intertwined during this period. However, this chapter examines not only competing modes of thought, but also the interconnections between them. It shows how theories about the relationship between religion and science arose out of a self-conscious response to other voices and were informed by exchange of ideas and open-ended debate.
Religious Change in the Mid-Tudor Period
Authors: King John N.
Published: August 2017

Mid-sixteenth-century England witnessed unprecedented religio-political turmoil. Following the death of Henry VIII in 1547, the government of Edward VI fostered a controversial programme of Protestant reform by instituting public worship in the vernacular based upon Bible readings, officially authorized sermons, and rejection of transubstantiation and replacement of the Mass with celebration of Holy Communion in the form of a communal meal in accordance with the second Book of Common Prayer (1552). The government relaxed restraints on Protestant propaganda at the same time that it blocked publication of Roman Catholic books. Following King Edward’s death in 1553, Mary I reversed changes in the state religion introduced under her late father and brother. Book publication underwent contraction as the government encouraged renewed publication of Roman Catholic books. Following the accession of Elizabeth I in 1558, her government restored Protestant doctrine and worship in line with the 1552 prayer book.
A 16 deg2 survey of emission-line galaxies at z < 1.5 in HSC-SSP Public Data Release 1
Authors: Hayashi Masao , Tanaka Masayuki , Shimakawa Rhythm , Furusawa Hisanori , Momose Rieko , Koyama Yusei , Silverman John D , Kodama Tadayuki , Komiyama Yutaka , Leauthaud Alexie , Lin Yen-Ting , Miyazaki Satoshi , Nagao Tohru , Nishizawa Atsushi J , Ouchi Masami , Shibuya Takatoshi , Tadaki Ken-ichi , Yabe Kiyoto
Published: August 2017

We present initial results from the Subaru Strategic Program (SSP) with Hyper Suprime-Cam (HSC) on a comprehensive survey of emission-line galaxies at z < 1.5 based on narrowband imaging. The first Public Data Release provides us with data from two narrowband filters, specifically NB816 and NB921 over 5.7 deg2 and 16.2 deg2 respectively. The 5 σ limiting magnitudes are 25.2 mag (UltraDeep layer, 1.4 deg2) and 24.8 mag (Deep layer, 4.3 deg2) for NB816, and 25.1 mag (UltraDeep, 2.9 deg2) and 24.6–24.8 mag (Deep, 13.3 deg2) for NB921. The wide-field imaging allows us to construct unprecedentedly large samples of 8054 H α emitters at z ≈ 0.25 and 0.40, 8656 [O iii] emitters at z ≈ 0.63 and 0.84, and 16877 [O ii] emitters at z ≈ 1.19 and 1.47. We map the cosmic web on scales out to about 50 comoving Mpc that includes galaxy clusters, identified by red sequence galaxies, located at the intersection of filamentary structures of star-forming galaxies. The luminosity functions of emission-line galaxies are measured with precision and are consistent with published studies. The wide field coverage of the data enables us to measure the luminosity functions up to brighter luminosities than previous studies. The comparison of the luminosity functions between the different HSC-SSP fields suggests that a survey volume of >5 × 105 Mpc3 is essential to overcome cosmic variance. Since the current data have not reached the full depth expected for the HSC-SSP, the color cut in i − NB816 or z − NB921 induces a bias towards star-forming galaxies with large equivalent widths, primarily seen in the stellar mass functions for the H α emitters at z ≈ 0.25–0.40. Even so, the emission-line galaxies clearly cover a wide range of luminosity, stellar mass, and environment, thus demonstrating the usefulness of the narrowband data from the HSC-SSP for investigating star-forming galaxies at z < 1.5.
Transfusion-related immunomodulation: a reappraisal
Authors: Youssef Lyla A. , Spitalnik Steven L.
Published: August 2017

Purpose of review

This review summarizes current and prior observations regarding transfusion-related immunomodulation (TRIM) and puts these ideas into a modern immunological context, incorporating concepts from innate, adaptive, and nutritional immunity. We propose that TRIM research focus on determining whether there are specific, well-defined immunosuppressive effects from transfusing ‘pure’ red blood cells (RBCs) themselves, along with the by-products produced by the stored RBCs as a result of the ‘storage lesion.’ Macrophages are a key cell type involved in physiological and pathological RBC clearance and iron recycling. The plasticity and diversity of macrophages makes these cells potential mediators of immune suppression that could constitute TRIM.

Recent findings

Recent reports identified the capacity of macrophages and monocytes to exhibit ‘memory.’ Exposure to various stimuli, such as engulfment of apoptotic cells and interactions with ß-glucan and lipopolysaccharide, were found to induce epigenetic, metabolic, and functional changes in certain myeloid cells, particularly macrophages and monocytes.

Macrophages may mediate the immunosuppressive aspects of TRIM that arise as a result of transfused RBCs and their storage lesion induced by-products.
The challenges of proprotein convertase subtilisin–kexin-9 inhibitors for lipid guidelines and models of care
Authors: Wierzbicki Anthony S.
Published: August 2017

Purpose of review

The article reviews the challenges facing cardiovascular disease (CVD) guidelines committees.

Recent findings

Clinical trials in high-risk populations have shown additional CVD event reduction with ezetimibe and proprotein convertase subtilisin–kexin-9 inhibitors. These trials recruit middle-aged secondary prevention populations, whereas increasingly the population at risk of CVD comprises the elderly in primary prevention. Some major guidelines have moved from a lipid-target to a risk-based approach. Some guidelines wish to preserve treatment targets to optimize the risk profile of individual patients as opposed to using population-based approaches. A numbers needed to treat approach has been suggested as a way of prioritizing patients for treatment, while retaining an individual's LDL cholesterol risk. However, the main barrier to implementation of some novel therapies in medicine is not their efficacy or safety but their cost. Health economic approaches that consider both benefits and costs can help guideline committees to define populations mostly likely to benefit.

The efficacy and expense of novel treatments is challenging traditional guideline development. Previously guideline committees used only to review clinical efficacy and safety endpoints but now they also have to consider costs to derive recommendations that are practical to implement.
Making up your mind: Enhanced perceptual decision-making induced by stochastic resonance during non-invasive brain stimulation: Stochastic resonance in perceptual decision-making
Authors: der Groen Onno van , Tang Matthew F. , Wenderoth Nicole , Mattingley Jason B.
Published: August 2017

Perceptual decision-making relies on the gradual accumulation of noisy sensory evidence until a specified boundary is reached and an appropriate response is made. It might be assumed that adding noise to a stimulus, or to the neural systems involved in its processing, would interfere with the decision process. But it has been suggested that adding an optimal amount of noise can, under appropriate conditions, enhance the quality of subthreshold signals in nonlinear systems, a phenomenon known asstochastic resonance. Here we asked whether perceptual decisions obey these stochastic resonance principles by adding noise directly to the visual cortex using transcranial random noise stimulation (tRNS) while participants judged the direction of motion in foveally presented random-dot motion arrays. Consistent with the stochastic resonance account, we found that adding tRNS bilaterally to visual cortex enhanced decision-making when stimuli were just below, but not well below or above, perceptual threshold. We modelled the data under a drift diffusion framework to isolate the specific components of the multi-stage decision process that were influenced by the addition of neural noise. This modelling showed that tRNS increased drift rate, which indexes the rate of evidence accumulation, but had no effect on bound separation or non-decision time. These results were specific to bilateral stimulation of visual cortex; control experiments involving unilateral stimulation of left and right visual areas showed no influence of random noise stimulation. Our study is the first to provide causal evidence that perceptual decision-making is susceptible to a stochastic resonance effect induced by tRNS, and that this effect arises from selective enhancement of the rate of evidence accumulation for sub-threshold sensory events.
Cellular phenotyping of hippocampal progenitors exposed to patient serum predicts conversion to Alzheimer’s Disease
Authors: Maruszak Aleksandra , Murphy Tytus , Liu Benjamine , de Lucia Chiara , Douiri Abdel , Nevado Alejo J , Teunissen Charlotte E , Visser Pieter Jelle , Price Jack , Lovestone Simon , Thuret Sandrine
Published: August 2017

The generation of new neurons persists into adulthood in the human hippocampus and can be modulated by the circulatory systemic environment. Hippocampal neurogenesis is important for learning and memory and is altered in Alzheimer’s Disease (AD). Evaluating the hippocampal neurogenic process during disease progression could therefore identify neurogenesis as an important target for AD prevention and intervention as well as a biomarker for early disease detection. In this study, we used a human hippocampal progenitor cell line to design an in vitro assay evaluating over time the neurogenic impact of the systemic milieu (i.e. serum) of individuals with mild cognitive impairment (MCI) as they either converted to AD or remained cognitively stable. Cells were exposed to serum collected over several years from the same patients. Cellular phenotyping and linear mixed effects models for repeated measures revealed that decreased proliferation, increased apoptotic hippocampal progenitor cell death and increased hippocampal neurogenesis characterized progression from MCI to AD. Using stepwise logistic regression and machine learning we show that these cellular readouts for the baseline serum sample and years of education of the patient are significant predictors of conversion from MCI to AD, already 3.5 years before AD clinical diagnosis. Finally, serum proteomic analyses indicated pathways linked to the cellular readouts distinguishing MCI to AD converters from non-converters. The proposed assay is thus not only promising for AD pre-clinical diagnosis, but it also provides a proxy into temporal changes of the hippocampal neurogenic process during disease progression.

One Sentence Summary

In this study, we demonstrate for the first time that the systemic environment (i.e. blood serum) of mild cognitively impaired patients differentially alters human hippocampal progenitor cell fate to predict conversion to Alzheimer’s Disease up to 3.5 years before clinical diagnosis.
Novel approach to quantitative spatial gene expression uncovers genetic stochasticity in the developingDrosophilaeye
Authors: Ali Sammi , Signor Sarah A. , Kozlov Konstantin , Nuzhdin Sergey V.
Published: August 2017

Robustness in development allows for the accumulation of neutral genetically based variation in expression, and here will be termed ‘genetic stochasticity‘. This largely neutral variation is potentially important for both evolution and complex disease phenotypes. However, it has generally only been investigated as variation exhibited in the response to large genetic perturbations. In addition, work on variation in gene expression has similarly generally been limited to being spatial, or quantitative, but because of technical restrictions not both. Here we bridge these gaps by investigating replicated quantitative spatial gene expression using rigorous statistical models, in different genotypes, sexes, and species (Drosophila melanogasterandD. simulans). Using this type of quantitative approach with developmental data allows for effective comparison among conditions, including health versus disease. We apply this approach to the morphogenetic furrow, a wave of differentiation that sweeps across the developing eye disc. Within the morphogenetic furrow, we focus on four conserved morphogens,hairy, atonal, hedgehog, andDelta. Hybridization chain reaction quantitatively measures spatial gene expression, co-staining for all four genes simultaneously and with minimal effort. We find considerable variation in the spatial expression pattern of these genes in the eye between species, genotypes, and sexes. We also find that there has been evolution of the regulatory relationship between these genes. Lastly, we show that the spatial interrelationships of these genes evolved between species in the morphogenetic furrow. This is essentially the first ‘population genetics of development’ as we are able to evaluate wild type differences in spatial and quantitative gene expression at the level of genotype, species and sex.
Forecasting crowd dynamics through coarse-grained data analysis
Authors: Motsch Sebastien , Moussaïd Mehdi , Guillot Elsa G. , Moreau Mathieu , Pettré Julien , Theraulaz Guy , Appert-Rolland Cécile , Degond Pierre
Published: August 2017

Understanding and predicting the collective behaviour of crowds is essential to improve the efficiency of pedestrian flows in urban areas and minimize the risks of accidents at mass events. We advocate for the development of a & “crowd forecasting system„whereby real-time observations of crowds are coupled to fast and reliable models to produce rapid predictions of the crowd movement and eventually help crowd managers choose between tailored optimization strategies. Here, we propose a Bi-directional Macroscopic (BM) model as the core of such a system. Its key input is the fundamental diagram for bi-directional flows, i.e. the relation between the pedestrian fluxes and densities. We design and run a laboratory experiments involving a total of 119 participants walking in opposite directions in a circular corridor and show that the model is able to accurately capture the experimental data in a typical crowd forecasting situation. Finally, we propose a simple segregation strategy for enhancing the traffic efficiency, and use the BM model to determine the conditions under which this strategy would be beneficial. The BM model, therefore, could serve as a building block to develop on the fly prediction of crowd movements and help deploying real-time crowd optimization strategies.
Caloric restriction mitigates age-associated hippocampal differential CG and non-CG methylation
Authors: Hadad Niran , Unnikrishnan Archana , Jackson Jordan A. , Masser Dustin R. , Otalora Laura , Stanford David R. , Richardson Arlan , Freeman Willard M.
Published: August 2017

Brain aging is marked by cognitive decline and susceptibility to neurodegeneration. Caloric-restriction (CR) increases neurogenesis, improves memory function, and protects from age-associated neurological disorders. Epigenetic mechanisms, including DNA methylation, are vital to normal CNS cellular and memory functions, and are dysregulated with aging. The beneficial effects of CR have been proposed to work through epigenetic processes, but this is largely unexplored. We therefore tested whether life-long CR prevents age-related DNA methylation changes in the brain. Hippocampal DNA from young (3 months) and old (24 months) male mice fedad libitumand 24 month old mice fed a 40% calorierestricted diet from 3 months of age were examined by genome-wide bisulfite sequencing to measure methylation with base-specificity. Over 27 million CG and CH (non-CG) sites were examined. Of the ~40,000 differentially methylated CGs (dmCGs) and ~80,000 CHs (dmCHs) with aging, >1/3 were prevented by CR and were found across genomic regulatory regions and gene pathways. CR also caused alterations to CG and CH methylation at sites not differentially methylated with aging, and these CR-specific changes demonstrated a different pattern of regulatory element and gene pathway enrichment than those affected by aging. CR-specific DNMT1 and TET3 promoter hypermethylation corresponded to reduced gene expression. These findings demonstrate that CR attenuates age-related CG and CH hippocampal methylation changes, in combination with CR-specific methylation that may also contribute to the neuroprotective effects of CR. The prevention of age-related methylation alterations is also consistent with the pro-longevity effects of CR working through an epigenetic mechanism.
Diverse modes of synaptic signaling, regulation, and plasticity distinguish two classes ofC. elegansglutamatergic neurons
Authors: Ventimiglia Donovan , Bargmann Cornelia I.
Published: August 2017

Synaptic vesicle release properties vary between neuronal cell types, but in most cases the molecular basis of this heterogeneity is unknown. Here, we comparein vivosynaptic properties of two neuronal classes in theC. eleganscentral nervous system, using VGLUT-pHluorin to monitor synaptic vesicle exocytosis and retrieval in intact animals. We show that the glutamatergic sensory neurons AWCONand ASH have distinct synaptic dynamics associated with tonic and phasic synaptic properties, respectively. Exocytosis in ASH and AWCONis differentially affected by SNARE-complex regulators that are present in both neurons: phasic ASH release is strongly dependent on UNC-13, whereas tonic AWCONrelease relies upon UNC-18 and on the protein kinase C homolog PKC-1. Exocytosis and retrieval each have two timescales in AWCONbut one major timescale in ASH. Strong stimuli that elicit high calcium levels also increase exocytosis and retrieval rates in AWCON, generating distinct tonic and evoked synaptic modes. These results highlight the differential deployment of shared presynaptic proteins in neuronal cell type-specific functions.
Maternal mRNAs with distinct 3′ UTRs define the temporal pattern of Ccnb1 synthesis during mouse oocyte meiotic maturation
Authors: Yang Ye , Yang Cai-Rong , Han Seung Jin , Daldello Enrico Maria , Cho Ara , Martins Joao P. Sousa , Xia Guoliang , Conti Marco
Published: August 2017

The final stages of female gamete maturation occur in the virtual absence of transcription, with gene expression driven by a program of selective unmasking, translation, and degradation of maternal mRNAs. Here we demonstrate that the timing of Ccnb1 mRNA translation in mouse oocytes is dependent on the presence of transcripts with different 3′ untranslated regions (UTRs). This 3′ UTR heterogeneity directs distinct temporal patterns of translational activation or repression. Inclusion or exclusion of cis-acting elements is responsible for these divergent regulations. Our findings reveal an additional layer of translation control through alternative polyadenylation usage required to fine-tune the timing of meiosis progression.
Hydrogen-bonded structures and interaction energies in two forms of the SGLT-2 inhibitor sotagliflozin
Authors: Gelbrich Thomas , Adamer Verena , Stefinovic Marijan , Thaler Andrea , Griesser Ulrich J.
Published: August 2017

The sotagliflozin molecule exhibits two fundamentally different molecular conformations in form 1 {systematic name: (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(methylsulfanyl)tetrahydro-2H-pyran-3,4,5-triol, C21H25ClO5S, (I)} and the monohydrate [C21H25ClO5S·H2O, (II)]. Both crystals display hydrogen-bonded layers formed by intermolecular interactions which involve the three –OH groups of the xyloside fragment of the molecule. The layer architectures of (I) and (II) contain a non-hydrogen-bonded molecule–molecule interaction along the short crystallographic axis (a axis) whose total PIXEL energy exceeds that of each hydrogen-bonded molecule–molecule pair. The hydrogen-bonded layer of (I) has the topology of the 4-connected sql net and that formed by the water and sotagliflozin molecules of (II) has the topology of a 3,7-connected net.
Crystal structure of the DNA sequence d(CGTGAATTCACG)2with DAPI
Authors: Sbirkova-Dimitrova Hristina I. , Shivachev Boris
Published: August 2017

The structure of 4′,6-diamidine-2-phenylindole (DAPI) bound to the synthetic B-DNA oligonucleotide d(CGTGAATTCACG) has been solved in space groupP212121by single-crystal X-ray diffraction at a resolution of 2.2 Å. The structure is nearly isomorphous to that of the previously reported crystal structure of the oligonucleotide d(CGTGAATTCACG) alone. The adjustments in crystal packing between the native DNA molecule and the DNA–DAPI complex are described. DAPI lies in the narrow minor groove near the centre of the B-DNA fragment, positioned over the A–T base pairs. It is bound to the DNA by hydrogen-bonding and van der Waals interactions. Comparison of the two structures (with and without ligand) shows that DAPI inserts into the minor groove, displacing the ordered spine waters. Indeed, as DAPI is hydrophobic it confers this behaviour on the DNA and thus restricts the presence of water molecules.