bluuebunny/crossref_metadata_2025 huggingface dataset:
English in North America
Authors: Hall-Lew Lauren
Published: February 2014

This chapter provides an overview of the complex and changing picture of English in North America, focusing both on historical development and contemporary internal diversity. Some of the major differences between North America and Britain are also discussed, and comparisons are drawn between the United States, Canada, and Mexico. The final section focuses on regional and social variation, drawing on both classic and contemporary research in sociolinguistics and dialectology.
Psychological, Behavioral, and Cognitive Changes During Pregnancy and the Postpartum Period
Authors: Miller Laura J.
Published: February 2014

Becoming pregnant and giving birth can lead to considerable psychological, behavioral, and cognitive transformation. The nature and scope of change varies a great deal from woman to woman. This chapter summarizes qualitative and quantitative research on normal psychological adaptation to pregnancy, including recognition and acceptance of the pregnant state, experience of the boundary between self and fetus, and body image changes. It reviews research on internal representations of the fetus and fetal and neonatal attachment. Perinatal changes in stress reactivity and coping style are reviewed. The chapter explains the influence of women’s prenatal expectations about labor and delivery on subsequent experiences and reactions and describes normative postpartum mood reactivity. Perinatal effects on sleep, physical activity, sexual activity, and eating patterns are described. Controversies about the effects of pregnancy on cognition are examined. The chapter also covers topics related to the transition to motherhood, including influences on maternal self-esteem and self-efficacy.
Understanding and Treating Infidelity
Authors: Howell Jennifer Willett , Gilbert Sarah E. , Gordon Kristina Coop
Published: February 2014

This chapter defines and describes different types of relationship infidelities and discusses existing research on understanding and treating infidelity. Studies examining the etiology, maintenance, and impact of infidelity in a relationship are reviewed and considered. The chapter then describes and critiques current empirically supported therapeutic approaches for treating infidelity, including a forgiveness-based intervention, traditional behavioral couple therapy, integrative behavioral couple therapy, and emotionally focused couple therapy. Important clinical considerations regarding cultural factors in conceptualizing and treating infidelity are addressed throughout the chapter and newer types of relationships and affairs (e.g., cyber affairs) also are discussed.
Relationships and Chronic Medical Problems
Authors: Pieczynski Jessica , Thilges Sarah , Bardsley Leland , Goldman Sher Tamara
Published: February 2014

This chapter provides an overview of the research on the reciprocal nature of illness and couple functioning. The chapter begins with a summary of the psychosocial literature, providing the context in which couples navigate illness, followed by a review of intermediate pathways through which relationship satisfaction and chronic illness interact. The chapter underscores the notion that chronic illness and couple functioning must be understood as a reciprocal, longitudinal feedback loop by highlighting the numerous couple and health processes that are interacting with each other over time to influence patient, partner, and health outcomes. Future directions and clinical implications are discussed.
Empirically Based Couple Relationship Education
Authors: Halford Kim , Petch Jemima , Bate Karina
Published: February 2014

Couple relationship education (CRE) is the provision of structured education intended to promote healthy couple relationships and prevent future relationship distress. CRE usually is brief, ranging in length from a single session (involving an assessment of the relationship with discussion of current strengths and challenges) to 12 to 14 hours of a skill-training curriculum. Research indicates that 10 or more hours of curriculum-based CRE produces short-term improvements in couple communication and relationship satisfaction; these findings have been well replicated. Though there is less research investigating the long-term effects of CRE, the available evidence suggests there is a benefit of CRE for couples at elevated risk of future relationship problems. Future research needs to further clarify which couples benefit from CRE, refine how CRE curriculum is tailored to address couples’ relationship needs, and enhance the reach of CRE to increase its community impact.
Couple Therapy with Same-Sex and Gender-Variant (LGBT) Couples
Authors: Mitchell Valory
Published: February 2014

Same-sex and gender-variant couples are similar to heterosexual/gender-traditional couples in many ways. However, lesbian, gay, and bisexual couples and couples with one or both transgender partners (LGBT couples) exist in a stigmatizing environment that provides no social structures for them. As a result, these couples face three types of challenges: minority stress, lack of social support, and role and relational ambiguity. The author reviews research on these three challenges and offers specific techniques to address them. A conceptual model creates a bridge between sociocultural challenges and the psychological-relational consequences, affording therapists an understanding of how to plan and implement effective interventions. In addition, seven basic premises provide parameters for work with LGBT couples.
Depressive Disorders, Comorbidity Issues, and Assessment Strategies
Authors: Eaton Nicholas R. , Krueger Robert F.
Published: February 2014

Assessment is at the very core of clinical and research endeavors to understand and ameliorate depressive disorders. In the current chapter, we discuss pressing issues in assessment of depressive disorders beginning with the definitional: how these disorders are conceptualized and classified. We highlight theDSM-IV-TRnosological organization of depressive disorders, and those disorders that are closely related (e.g., anxiety and adjustment disorders), as well as current depressive disorder proposals for the upcomingDSM-5. The high rates of comorbidity among the depressive and related disorders are discussed as an assessment challenge, and we propose a unified latent structure framework to supplement clinical assessment that involves characterizing individuals’ levels of underlying internalizing disorder liability. We discuss how disorders, and the latent internalizing liability, may manifest differently across subpopulations, such as age and ethnicity/culture. Finally, we discuss psychometric issues and conclude with a list of critical unanswered questions in depressive disorder assessment.
Comorbidity of Bipolar Disorder and Depression
Authors: Youngstrom Eric , Van Meter Anna
Published: February 2014

There has been speculation about the relationship between depression and mania for centuries. Modern psychiatry and psychology have mostly viewed these as different subtypes within a “family” of mood disorders. Conceptual models of comorbidity provide an opportunity to re-examine the association between depression and other pathological mood states. We examine the evidence pertaining to rates of “comorbidity,” which, in this case, refer to the lifetime occurrence of depression and hypomanic, mixed, or manic episodes in the same individual. We explore factors that could contribute to artifactual comorbidity. We also examine data pertaining to similarities or differences in phenomenology, longitudinal course, associated features, family history, and treatment response. Multiple factors are likely involved in the comorbidity of depression and hypomania or mania, and the problems of poor reliability and inconsistent diagnostic definitions and methodology attenuate the significance of most research findings. However, evidence appears sufficient to conclude that not all depression is on the bipolar spectrum, that bipolar features moderate the course and outcome of depressive illness, and that depression and bipolar disorder most likely involve a blend of some shared and some specific mechanisms. Research and clinical work both will advance substantially by more systematically assessing for potential bipolar features “comorbid” with depression and following how these factors change the trajectory of depression over time.
From Comorbidity to Constructs
Authors: Markon Kristian E.
Published: February 2014

Comorbidity models have become central to psychopathology theory and research, not only because they have clarified our understanding of how and why disorders co-occur but also because they have clarified our understanding of what the disorders are. This chapter reviews basic types of comorbidity models, recurring issues in comorbidity modeling, and discuss emerging issues in the area. Using recent epidemiological, repeated-measures data on depression and anxiety as an example, two different models of comorbidity are compared, one in which comorbidity arises due a shared liability dimension (i.e., a reflective or latent variable model) and another in which comorbidity arises as an epiphenomenon of correlated symptoms (i.e., a formative or network model). This comparison, relatively novel in the literature, illustrates a number of issues that are encountered in comorbidity modeling, and clearly demonstrates how questions pertaining to comorbidity can shape our understanding of psychopathology constructs.
Focus Group Research
Authors: Kamberelis George , Dimitriadis Greg
Published: February 2014

This essay is both historical and conceptual, first highlighting the origins, tensions, and continuities/discontinuities of focus group research, then arguing for how such research embodies three primary, related functions: inquiry, pedagogy, and political. The quasi-unique potentials or affordances of focus group work are explored, including mitigating the researcher’s authority; disclosing the constitutive power of discourse; approximating the natural; filling in knowledge gaps and saturating understanding; drawing out complexity, nuance, and contradiction; disclosing eclipsed connections; and creating opportunities for political activism. Contemporary threats to focus group work are described, and new research frontiers are proposed, especially in relation to new information technologies. The essay integrates historical, conceptual, and practical perspectives to fully explain the potentials of focus group research, with the goal of advancing a set of understandings about focus group work that attends to its relatively unique potentials for conducting qualitative inquiry across a wide range of topics and disciplinary contexts.
Tyrannicide in Ancient Greek Political Culture
Authors: Teegarden David A.
Published: February 2014

This chapter provides an analytical framework for interpreting the history of tyrannicide in ancient Greece. It first explores the Athenians’ idealization of Harmodius and Aristogeiton—two Athenian tyrannicides—during the late archaic and early classical periods. Next, it analyzes the subsequent promotion of tyrannicide outside of Athens: on the Greek mainland in the late classical period; in western Asia Minor during the early Hellenistic period; in the Peloponnesus during the third century B.C.E. Finally, it accounts for the popularity of tyrannicide in ancient Greek political culture, arguing that such acts helped democracy supporters mobilize against nondemocratic regimes and were not considered to be problematic.
Instrumental Terror in Medieval Europe
Authors: Brown Warren C.
Published: February 2014

This article argues that the modern concept of terrorism does not fit the realities or worldviews that characterize medieval societies. Instead, therefore, the article explores the wider use of instrumental terror in the period, that is, the deliberate use of extreme fear to achieve some goal or set of goals indirectly, rather than by the direct application of force. It concludes that instrumental terror formed an important part of the repertoire of power in medieval Europe. It was most often applied through violence wielded from the top down, by people wishing to impose or maintain their power over others. It was occasionally, however, used from the bottom up, in an effort to destabilize or overturn a dominant order. Its legitimacy was subjective; while some medieval sources condemn it, others present it as necessary and even positive.
Ismaili Assassins as Early Terrorists?
Authors: Cook David
Published: February 2014

The idea that the Ismaili Assassins, historically flourishing during the eleventh–thirteenth centuries, provided by their suicidal attacks on prominent Muslim and Crusader figures a type of inspiration for contemporary suicide attackers has been a popular one in recent literature. While the Ismaili attacks were targeted rather than terroristic in nature, there is no evidence that the assassins either sought death or that their actions could be accomplished solely through the deaths of their perpetrators. Their assassinations in fact can be explained within the context of Ismaili religious thought of that time and constitute an abortive development in the doctrine of Shi`ite jihad.
“Thugs and Assassins,” “New Terrorism” and the Resurrection of Colonial Knowledge
Authors: Wagner Kim A.
Published: February 2014

Since the publication in 1984 of David C. Rapoport’s article “Fear and Trembling: Terrorism in Three Religious Traditions,” it has become commonplace to assume that historical practices such as “Thuggee” in India constitute appropriate comparisons to modern terrorism. This invocation of history has provided the foundation for the “New Terrorism” paradigm, which has enjoyed an unprecedented impact on policymaking and has, alongside the “Clash of Civilizations” thesis, provided the “academic” legitimation for the ongoing “War on Terror.” Paradoxically, this reading of history has resulted in an entirely ahistorical analysis, which sees the so-called “religious terrorist” as a two-dimensional stereotype causing havoc through the millennia unaffected by historical change or contextual specificity. This chapter examines the resurrection of colonial knowledge by modern terrorism experts and the reinvention of the nineteenth-century “Thugs” as ideological predecessors to the “religious terrorists” of today.
Propaganda of the Deed
Authors: Larabee Ann
Published: February 2014

This chapter discusses the emergence of a controversial genre of radical discourse—the popular weapons manual—among anti-imperial, anticapitalist groups in the United States and Europe during the late 1870s. Drawn from science textbooks, military manuals, and other types of technical literature, the new discourse synthesized information from authoritative sources, made technical processes accessible to the average reader, and politicized the practice of technical education. The chapter uses bomb-making texts such as the enigmatic Professor Mezzeroff’s “Prescriptions for Students” and Johann Most’s Science of Revolutionary Warfare to show that the democratization of science and technology was critical to the historical emergence of terrorism.
Anarchist Terrorism in Fin de Siècle France and its Borderlands
Authors: Bouhey Vivien
Published: February 2014

In contrast to traditional historiography, which insists on the absence of organization within the anarchist movement and on the individual character of propaganda by the deed, this chapter situates anarchist attacks in the context of a more structured movement that operated on a local, regional, national, and international scale. This movement was not, however, identical to the “Black International,” the fantasy of a small group giving orders to disciplined operatives that was dreamt up at the time by, among others, police informants and journalists. The chapter shows how, although some attacks were indeed individual and spontaneous, others were carefully prepared by local, regional, national, and cross-border networks whose members benefited from active solidarity within the movement and together managed to terrorize the Third Republic.
China and the “Anarchist Wave of Assassinations” around the Turn of the Twentieth Century
Authors: Müller-Saini Gotelind
Published: February 2014

This chapter discusses the reception of what David Rapoport has called the “anarchist wave of assassinations” as the first wave of global terrorism in East Asia at the turn of the twentieth century. It shows how the terms “terrorism” and “anarchism” were translated into East Asian languages; how the practice of assassinations relates to indigenous traditions of political violence; and in which sense one can speak of “modernity” in the Chinese assassination attempts undertaken. What interested the radicals receiving European models most was the perceived “new” strategy of systematic assassination campaigns as lived out by the Russian Narodnaya Volya, and its potential for “new” groups of people to join political violence, namely women. This strategy was attractive for a time to many kinds of ideological commitments, but especially to the Chinese Nationalists. Thus, this chapter calls into question the definition of the “first wave” in Rapoport’s “four wave concept” as “anarchist.”
“Oriental” Terrorism, Counterinsurgency, and the End of the Ottoman Empire
Authors: Gingeras Ryan
Published: February 2014

This chapter deals with the impact and legacy of the Internal Macedonian Revolutionary Organization upon the final years of the Ottoman Empire. Two critical themes are at the center of this study. First, it deals with the ways in which the VMRO (as the group is most commonly termed) was perceived as a representation of terrorism and culture in Ottoman Macedonia by both foreign and native sources. Second, it surveys the Ottoman state’s development of a counterinsurgency strategy to counter the likes of the VMRO and the long-term influence this program had upon the final years of the empire itself. In this later regard, the chapter traces the origins of the Ottoman “çete” (or paramilitary culture) of the Committee for Union and Progress (CUP) to the establishment Special Organization (Teskilat-i Mahsusa) during the World War I.
Manifestations of Imperial Terror in Colonial Kenya
Authors: Parsons Timothy H.
Published: February 2014

This chapter analyzes political violence in Kenya from the late nineteenth century to the 1960s. In a study of the “pacification campaigns” conducted by the Imperial British East Africa Company against the Kikuyu and Nandi communities at the turn of the twentieth century, the chapter describes the use of spectacular violence on both sides. It then offers an explanation for why there were no major outbursts of political violence during the Kenyan colonial regime. Finally, it analyzes the internal struggle in post–World War II Kenya known as the “Mau Mau Emergency,” which has conventionally been characterized as a nationalist uprising but which was in fact a Kikuyu civil war that had the effect of a neo-pacification campaign. The chapter thus calls into question basic assumptions about powerless nonstate actors and a powerful state, inviting a reevaluation of these ideas by scholars of terrorism.
Policing Anarchist Migration across the Atlantic
Authors: Jensen Richard Bach
Published: February 2014

The migration of large numbers of working-class Italians to Argentina during the nineteenth century helped to make Buenos Aires the largest and most important anarchist community in the world by the 1890s. This chapter compares the cooperative efforts of the Italian and Argentine governments and police forces to monitor this migration, to restrict anarchists’ mobility by denying them entry into the respective countries, and to detect and prevent incipient acts of violence. The success and failure of these efforts had a significant influence on national counterterrorism policies: the liberal Italian policy effectively curtailed anarchists and workers’ violence in the short run, while the overreaction of the Argentine government was a crucial factor in provoking a previously moderate anarchist community toward the use of violence.
Mission Music as a Mode of Intercultural Transmission, Charisma, and Memory in Northern Australia
Authors: Magowan Fiona
Published: February 2014

This article, focuses on the durability of Methodist “mission music” among the Yolngu, an Australian Indigenous people, and addresses questions of musical transfer between missionaries and Yolngu over fifty years that have shaped their Christian music politics. “Mission music” is marked as a genre by its association with the early missionaries among the Yolngu, their processes of teaching and transmission and its articulation with some aspects of Yolngu ritual performance practices. Today, mission music is performed together with an array of contemporary Christian musics reflecting its ongoing importance as a local, transnational and international currency. Magowan shows how hymnody has persisted for Yolngu as a musical mode of remembering and celebrating the past, illustrated first in early dialogic approaches to music teaching and choral training, and later recaptured in choral performances for the 50th anniversary festival of a Yolngu mission. She argues that “mission music,” in spite of its introduced, non-local origins, has become an experiential, rhythmical and textual sign of the “local” as it is adopted and used by the Yolngu. Choral singing is shown to be a means of embodying mission memories and facilitating local charismatic leadership, in turn, transforming Yolngu-missionary relationships over time. Ongoing work with missionary evangelists and frequent travel to foreign mission fields have also created new arenas for intercultural dialogue, leading to increasing complexity in Yolngu relationships embodied in Christian performance.
The Renaissance of the Corsican Confraternities and Their Musical Negotiations
Authors: Bithell Caroline
Published: February 2014

Caroline Bithell’s essay offers a history of a local religious institution—the Corsican confraternity—which constructs itself as a local alternative to a global religious bureaucracy—the Catholic hierarchy. She traces the musical life of the confraternities between the late 20th and early 21st centuries, and comments on the contemporary role played by the confraternities in both church and society. The distinctive polyphonic song repertoires of the confraternities are central to their identities, negotiated with contemporary church and Corsican institutions. In sum, in Corsica, the confraternities provide an alternate institutional space for (conservative) local musical and expressive traditions to continue, despite the shifts in musical and liturgical practices stemming from Vatican II.
Local Music Making and the Liturgical Renovation in Minas Gerais
Authors: Reily Suzel Ana
Published: February 2014

Suzel Reily’s essay discusses the implication of the universalist thrust of the Roman Catholic Church upon local traditions. While in Brazil local music making has been historically linked to Catholic practice, the clergy’s understandings of “the popular” derive from their interpretations of Vatican II directives along with a preoccupation with liturgical fidelity. In this setting, lay religious repertoires are being discouraged in favor of folk-like musics rooted in imagined local traditions. But alongside a clash in musical aesthetics, Reily shows how the musical practices associated with the new repertoire actually mitigate against collective singing, whilst threatening to shift local practices from the religious sphere to, at best, a secular folklorized arena.
American Muslims in the Age of New Media
Authors: Khan Nadia
Published: February 2014

The article explores how American Muslim activists increasingly use the power of social media to change the discourse about American Muslims. First, it provides a sketch of the American Muslim web presence, followed by an exploration of the American Muslim webscape’s topography. Second, it investigates how American Muslim religious leaders operate online. While some posit that the Internet can erode their authority, American Muslim religious leaders and institutions have leveraged new media to expand their following online. Third, it examines how the Internet not only fosters linkages between American Muslims and their coreligionists abroad but also, more importantly, how American Muslims use the Internet to emphasize their identity as diverse, law-abiding citizens. Finally, it shows how American Muslims use the Internet—not simply to propagate their faith but to deflect anti-Muslim sentiment and make claims for equal citizenship.
Da‘wa in the United States
Authors: Moore Kathleen M.
Published: February 2014

Da’wa (literally, "call") refers not only to missionary work (i.e., spreading the message of Islam to nonbelievers). It also means reinforcing greater piety on the part of Muslims, appealing to Muslims to renew their religious commitment. Influenced by Muslim scholar Isma’il al-Faruqi, contemporary da’wa activity in the American context has underscored that the role of the da’i (the one who calls) is to invite "reversion" to one's natural or innate state of being in relationship with the divine. Islam was readopted by many twentieth-century African Americans due to da’wa work of the Ahmadis, the Nation of Islam, and others. Digital da’wa, using new social media and the Internet, and visual da’wa (e.g., satellite television and YouTube videos) add innovative means to propagating the faith and increasing Islamic literacy.
Improvisation and Interaction, Canons and Rules, Emergence and Play
Authors: Penny Simon
Published: February 2014

This chapter explores the relationship between computer-based interactivity and improvisation with respect to traditions in the arts and to discourses in biology and computer science. In relation to traditional practices in the fine arts, both improvisation and computer-based interactive art are identified as model systems that, in contradistinction to traditional practices, exhibit temporally ongoing novel behavior in response to an environmental context. Modeling, designing, or enacting behavior with respect to environment is discussed in biological and ecological terms. Concepts from ethology, cybernetics, systems theory, autopoietic biology, artificial intelligence, and artificial life are introduced to further explore qualities of emergence, generativity, agency, and performativity in improvisation and interaction. Several exemplary improvisatory, interactive, and artificial life artworks are discussed in these terms.
Cultural Trauma and Religious Identity
Authors: Giesen Bernhard
Published: February 2014

Based on Niklas Luhmann’s argument, religion may be viewed as any communication governed by the distinction between immanence and transcendence. While some societies dispose of a religious foundation, others reject a presupposition of their unity with other societies that accounts for meaningful intersocietal communications. These presuppositions, despite the certainty with which they are held, are difficult to describe and can hardly be discarded with cultural discourse. This essay explores the notion of cultural trauma and its relation to religious identity. It first explains the concept of collective identity and how it differs from individual identity. It then turns to a discussion of triumphant heroism and the revolutionary origin of the demos. It also examines the liminality of the tragically failing hero, along with the collective identity and liminality of victims in contrast to that of heroes and perpetrators. The essay concludes with a discussion of the contemporary shift from triumphant to traumatic foundations of collective memory, as reflected in rituals and monuments.
Progenitor type identification for supernova remnant N103B in the Large Magellanic Cloud by Suzaku and Chandra observations
Authors: Someya Kentaro , Bamba Aya , Ishida Manabu
Published: February 2014

This paper presents a detailed analysis of supernova remnant (SNR) N103B located in the Large Magellanic Cloud (LMC), based on Suzaku and Chandra observations. The spectrum of the entire remnant was closely reproduced by using three interstellar medium (ISM) components with temperatures of ∼ 0.32, ∼ 0.56, and ∼ 0.92 keV and one ejecta component with ∼ 3.96 keV, based on a spectral analysis of the Suzaku/X-ray Imaging Spectrometer (XIS) data. The ejecta was overabundant in heavy elements, such as Mg, Si, S, Ca, Fe, and Ni. The unprecedentedly high quality of data obtained with Suzaku/XIS allowed us to correctly distinguish between two emissions from the ISM and the ejecta for the first time in a spectral analysis. Combining the spectral analysis of XIS data with the image analysis based on Chandra/Advanced CCD Imaging Spectrometer (ACIS) data, we verified that the ejecta distributions for elements from Si to Fe-K were similar to one another, although the Fe-K emission was located slightly inward compared with that of the lighter elements such as Si, S, Ar, and Ca. We compared hydrogen-rich ejecta plasma (called “H-dominated plasma”), which is indicative of Type II SNRs, with plasma rich in heavy elements and poor in hydrogen (called “pure metal plasma”) mainly observed in Type Ia SNRs. High-energy continuum images in the 5.2–6.0 keV band obtained with ACIS were extremely similar to those of the ejecta, implying that the origin of the high-energy continuum might indeed be the ejecta. By combining spectral analyses and high-energy continuum images, we found some indications for H-dominated plasma, and showed, that the progenitor of N103B might have been a Type II supernova. The progenitor mass was estimated to be 13 M⊙ based on the abundance patterns of Mg, Fe, and Ni relative to Si.
Reversal of Monoarthritis-induced Affective Disorders by Diclofenac in Rats
Authors: Borges Gisela , Neto Fani , Mico Juan Antonio , Berrocoso Esther
Published: February 2014

Background:

Nonsteroidal anti-inflammatory drugs are effective for arthritic pain, but it is unknown whether they also benefit anxiety and depression that frequently coexist with pain. Using the monoarthritis model, the authors evaluated the activation of extracellular signal–regulated kinases 1 and 2 (ERK1/2) in structures implicated in both sensorial and emotional pain spheres, and it was verified whether analgesia can reverse monoarthritis-mediated affective responses.

Methods:

Monoarthritis was induced in male rats by complete Freund’s adjuvant injection. Allodynia (ankle-bend test), mechanical hyperalgesia (paw-pinch test), anxiety- and depression-like behaviors (elevated zero maze and forced swimming tests, respectively), and ERK1/2 phosphorylation (Western blot) in the spinal cord, paragigantocellularis nucleus, locus coeruleus, and prefrontal cortex were evaluated at 4, 14, and 28 days postinoculation (n = 6 per group). Changes in these parameters were evaluated after induction of analgesia by topical diclofenac (n = 5 to 6 per group).

Results:

Despite the pain hypersensitivity and inflammation throughout the testing period, chronic monoarthritis (28 days) also resulted in depressive- (control [mean ± SEM]: 38.3 ± 3.7 vs. monoarthritis: 51.3 ± 2.0; P < 0.05) and anxiogenic-like behaviors (control: 36.8 ± 3.7 vs. monoarthritis: 13.2 ± 2.9; P < 0.001). These changes coincided with increased ERK1/2 activation in the spinal cord, paragigantocellularis, locus coeruleus, and prefrontal cortex (control vs. monoarthritis: 1.0 ± 0.0 vs. 5.1 ± 20.8, P < 0.001; 0.9 ± 0.0 vs. 1.9 ± 0.4, P < 0.05; 1.0 ± 0.3 vs. 2.9 ± 0.6, P < 0.01; and 1.0 ± 0.0 vs. 1.8 ± 0.1, P < 0.05, respectively). Diclofenac decreased the pain threshold of the inflamed paw and reversed the anxio-depressive state, restoring ERK1/2 activation levels in the regions analyzed.

Conclusion:

Chronic monoarthritis induces affective disorders associated with ERK1/2 phosphorylation in paragigantocellularis, locus coeruleus, and prefrontal cortex which are reversed by diclofenac analgesia. (Anesthesiology 2014; 120:1476-90)
The immunologic V-gene repertoire in mammals
Authors: Olivieri David , von Haeften Bernardo , Sánchez-Espinel Christian , Gambón-Deza Francisco
Published: February 2014

abstract

From recent whole genome shotgun data of 48 mammalian species, we have used our software VgenExtractor to obtain the functional V-gene sequence repertoire in order to conduct comparative phylogenetic studies. These studies reveal a large variation in the number of V-genes across mammalian species, ranging from a mere 36 V-genes in dolphins to nearly 600 V-genes in rats. Monotremes and marsupials are the only mammals possessing an additional locus, the TRMV, apart from the seven common loci found in mammals. Also, we show evidence for the loss of the light chain loci, specifically the Vκchain in one microbat, and the Vλchain in one rodent species. Finally, we suggest different features related to the evolution of immunoglobulin and T cell receptor loci, where frequent sequence duplications are seen in the former, while preserved and undiversified lineages are observed in the latter. All the V-gene sequences described in this study are available in the public database repositoryvgenerepertoire.org.
Non-specificity of Pitstop 2 in clathrin-mediated endocytosis
Authors: Willox Anna K , Sahraoui Yasmina M.E. , Royle Stephen J
Published: February 2014

Small molecule inhibitors of clathrin-mediated endocytosis are highly desired for the dissection of membrane trafficking pathways in the lab and for potential use as anti-infectives in the clinic. One inhibition strategy is to prevent clathrin from contacting adaptor proteins so that clathrin-mediated endocytosis cannot occur. "Pitstop" compounds have been developed which block only one of the four functional interaction sites on the N-terminal domain of clathrin heavy chain. Despite this limitation, Pitstop 2 causes profound inhibition of clathrin-mediated endocytosis. In this study, we probed for non-specific activity of Pitstop 2 by examining its action in cells expressing clathrin heavy chain harbouring mutations in the N-terminal domain interaction sites. We conclude that the inhibition observed with this compound is due to non-specificity, i.e. it causes inhibition away from its proposed mode of action. We recommend that these compounds be used with caution in cells and that they should not be used to conclude anything of the function of clathrin’s N-terminal domain.
Divergence in a master variator generates distinct phenotypes and transcriptional responses
Authors: Gallagher Jennifer E.G. , Zheng Wei , Rong Xiaoqing , Miranda Noraliz , Lin Zhixiang , Dunn Barbara , Zhao Hongyu , Snyder Michael P.
Published: February 2014

Genetic basis of phenotypic differences in individuals is an important area in biology and personalized medicine. Analysis of divergent Saccharomyces cerevisiae strains grown under different conditions revealed extensive variation in response to both drugs (e.g., 4-nitroquinoline 1-oxide [4NQO]) and different carbon sources. Differences in 4NQO resistance were due to amino acid variation in the transcription factor Yrr1. Yrr1YJM789 conferred 4NQO resistance but caused slower growth on glycerol, and vice versa with Yrr1S96, indicating that alleles of Yrr1 confer distinct phenotypes. The binding targets of Yrr1 alleles from diverse yeast strains varied considerably among different strains grown under the same conditions as well as for the same strain under different conditions, indicating that distinct molecular programs are conferred by the different Yrr1 alleles. Our results demonstrate that genetic variations in one important control gene (YRR1), lead to distinct regulatory programs and phenotypes in individuals. We term these polymorphic control genes “master variators.”
Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex
Authors: Hiraga Shin-ichiro , Alvino Gina M. , Chang FuJung , Lian Hui-yong , Sridhar Akila , Kubota Takashi , Brewer Bonita J. , Weinreich Michael , Raghuraman M.K. , Donaldson Anne D.
Published: February 2014

Initiation of eukaryotic DNA replication requires phosphorylation of the MCM complex by Dbf4-dependent kinase (DDK), composed of Cdc7 kinase and its activator, Dbf4. We report here that budding yeast Rif1 (Rap1-interacting factor 1) controls DNA replication genome-wide and describe how Rif1 opposes DDK function by directing Protein Phosphatase 1 (PP1)-mediated dephosphorylation of the MCM complex. Deleting RIF1 partially compensates for the limited DDK activity in a cdc7-1 mutant strain by allowing increased, premature phosphorylation of Mcm4. PP1 interaction motifs within the Rif1 N-terminal domain are critical for its repressive effect on replication. We confirm that Rif1 interacts with PP1 and that PP1 prevents premature Mcm4 phosphorylation. Remarkably, our results suggest that replication repression by Rif1 is itself also DDK-regulated through phosphorylation near the PP1-interacting motifs. Based on our findings, we propose that Rif1 is a novel PP1 substrate targeting subunit that counteracts DDK-mediated phosphorylation during replication. Fission yeast and mammalian Rif1 proteins have also been implicated in regulating DNA replication. Since PP1 interaction sites are evolutionarily conserved within the Rif1 sequence, it is likely that replication control by Rif1 through PP1 is a conserved mechanism.
The methyltransferase G9a regulates HoxA9-dependent transcription in AML
Authors: Lehnertz Bernhard , Pabst Caroline , Su Le , Miller Michelle , Liu Feng , Yi Lin , Zhang Regan , Krosl Jana , Yung Eric , Kirschner Jeanette , Rosten Patty , Underhill T. Michael , Jin Jian , Hébert Josée , Sauvageau Guy , Humphries R. Keith , Rossi Fabio M.
Published: February 2014

Chromatin modulators are emerging as attractive drug targets, given their widespread implication in human cancers and susceptibility to pharmacological inhibition. Here we establish the histone methyltransferase G9a/EHMT2 as a selective regulator of fast proliferating myeloid progenitors with no discernible function in hematopoietic stem cells (HSCs). In mouse models of acute myeloid leukemia (AML), loss of G9a significantly delays disease progression and reduces leukemia stem cell (LSC) frequency. We connect this function of G9a to its methyltransferase activity and its interaction with the leukemogenic transcription factor HoxA9 and provide evidence that primary human AML cells are sensitive to G9A inhibition. Our results highlight a clinical potential of G9A inhibition as a means to counteract the proliferation and self-renewal of AML cells by attenuating HoxA9-dependent transcription.
Crystal structures of substrate-bound chitinase from the psychrophilic bacterium Moritella marina and its structure in solution
Authors: Malecki Piotr H. , Vorgias Constantinos E. , Petoukhov Maxim V. , Svergun Dmitri I. , Rypniewski Wojciech
Published: February 2014

The four-domain structure of chitinase 60 from Moritella marina (MmChi60) is outstanding in its complexity. Many glycoside hydrolases, such as chitinases and cellulases, have multi-domain structures, but only a few have been solved. The flexibility of the hinge regions between the domains apparently makes these proteins difficult to crystallize. The analysis of an active-site mutant of MmChi60 in an unliganded form and in complex with the substrates NAG4 and NAG5 revealed significant differences in the substrate-binding site compared with the previously determined complexes of most studied chitinases. A SAXS experiment demonstrated that in addition to the elongated state found in the crystal, the protein can adapt other conformations in solution ranging from fully extended to compact.
Structural insights into the molecular mechanism of Escherichia coli SdiA, a quorum-sensing receptor
Authors: Kim Truc , Duong Thao , Wu Chun-ai , Choi Jongkeun , Lan Nguyen , Kang Sung Wook , Lokanath Neratur K. , Shin DongWoo , Hwang Hye-Yeon , Kim Kyeong Kyu
Published: February 2014

Escherichia coli SdiA is a quorum-sensing (QS) receptor that responds to autoinducers produced by other bacterial species to control cell division and virulence. Crystal structures reveal that E. coli SdiA, which is composed of an N-terminal ligand-binding domain and a C-terminal DNA-binding domain (DBD), forms a symmetrical dimer. Although each domain shows structural similarity to other QS receptors, SdiA differs from them in the relative orientation of the two domains, suggesting that its ligand-binding and DNA-binding functions are independent. Consistently, in DNA gel-shift assays the binding affinity of SdiA for the ftsQP2 promoter appeared to be insensitive to the presence of autoinducers. These results suggest that autoinducers increase the functionality of SdiA by enhancing the protein stability rather than by directly affecting the DNA-binding affinity. Structural analyses of the ligand-binding pocket showed that SdiA cannot accommodate ligands with long acyl chains, which was corroborated by isothermal titration calorimetry and thermal stability analyses. The formation of an intersubunit disulfide bond that might be relevant to modulation of the DNA-binding activity was predicted from the proximal position of two Cys residues in the DBDs of dimeric SdiA. It was confirmed that the binding affinity of SdiA for the uvrY promoter was reduced under oxidizing conditions, which suggested the possibility of regulation of SdiA by multiple independent signals such as quorum-sensing inducers and the oxidation state of the cell.
Role of κ→λ light-chain constant-domain switch in the structure and functionality of A17 reactibody
Authors: Ponomarenko Natalia , Chatziefthimiou Spyros D. , Kurkova Inna , Mokrushina Yuliana , Mokrushina Yuliana , Stepanova Anastasiya , Smirnov Ivan , Avakyan Marat , Bobik Tatyana , Mamedov Azad , Mitkevich Vladimir , Belogurov Alexey , Fedorova Olga S. , Dubina Michael , Golovin Andrey , Lamzin Victor , Friboulet Alain , Makarov Alexander A. , Wilmanns Matthias , Gabibov Alexander
Published: February 2014

The engineering of catalytic function in antibodies requires precise information on their structure. Here, results are presented that show how the antibody domain structure affects its functionality. The previously designed organophosphate-metabolizing reactibody A17 has been re-engineered by replacing its constant κ light chain by the λ chain (A17λ), and the X-ray structure of A17λ has been determined at 1.95 Å resolution. It was found that compared with A17κ the active centre of A17λ is displaced, stabilized and made more rigid owing to interdomain interactions involving the CDR loops from the VL and VH domains. These VL/VH domains also have lower mobility, as deduced from the atomic displacement parameters of the crystal structure. The antibody elbow angle is decreased to 126° compared with 138° in A17κ. These structural differences account for the subtle changes in catalytic efficiency and thermodynamic parameters determined with two organophosphate ligands, as well as in the affinity for peptide substrates selected from a combinatorial cyclic peptide library, between the A17κ and A17λ variants. The data presented will be of interest and relevance to researchers dealing with the design of antibodies with tailor-made functions.
Ensemble refinement shows conformational flexibility in crystal structures of human complement factor D
Authors: Forneris Federico , Burnley B. Tom , Gros Piet
Published: February 2014

Human factor D (FD) is a self-inhibited thrombin-like serine proteinase that is critical for amplification of the complement immune response. FD is activated by its substrate through interactions outside the active site. The substrate-binding, or `exosite', region displays a well defined and rigid conformation in FD. In contrast, remarkable flexibility is observed in thrombin and related proteinases, in which Na+ and ligand binding is implied in allosteric regulation of enzymatic activity through protein dynamics. Here, ensemble refinement (ER) of FD and thrombin crystal structures is used to evaluate structure and dynamics simultaneously. A comparison with previously published NMR data for thrombin supports the ER analysis. The R202A FD variant has enhanced activity towards artificial peptides and simultaneously displays active and inactive conformations of the active site. ER revealed pronounced disorder in the exosite loops for this FD variant, reminiscent of thrombin in the absence of the stabilizing Na+ ion. These data indicate that FD exhibits conformational dynamics like thrombin, but unlike in thrombin a mechanism has evolved in FD that locks the unbound native state into an ordered inactive conformation via the self-inhibitory loop. Thus, ensemble refinement of X-ray crystal structures may represent an approach alternative to spectroscopy to explore protein dynamics in atomic detail.
The structure of an authentic spore photoproduct lesion in DNA suggests a basis for recognition
Authors: Singh Isha , Lian Yajun , Li Lei , Georgiadis Millie M.
Published: February 2014

The spore photoproduct lesion (SP; 5-thymine-5,6-dihydrothymine) is the dominant photoproduct found in UV-irradiated spores of some bacteria such as Bacillus subtilis. Upon spore germination, this lesion is repaired in a light-independent manner by a specific repair enzyme: the spore photoproduct lyase (SP lyase). In this work, a host–guest approach in which the N-terminal fragment of Moloney murine leukemia virus reverse transcriptase (MMLV RT) serves as the host and DNA as the guest was used to determine the crystal structures of complexes including 16 bp oligonucleotides with and without the SP lesion at 2.14 and 1.72 Å resolution, respectively. In contrast to other types of thymine–thymine lesions, the SP lesion retains normal Watson–Crick hydrogen bonding to the adenine bases of the complementary strand, with shorter hydrogen bonds than found in the structure of the undamaged DNA. However, the lesion induces structural changes in the local conformation of what is otherwise B-form DNA. The region surrounding the lesion differs significantly in helical form from B-DNA, and the minor groove is widened by almost 3 Å compared with that of the undamaged DNA. Thus, these unusual structural features associated with SP lesions may provide a basis for recognition by the SP lyase.
1-(2-Methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl acetate
Authors: Shahid Hafiz Abdullah , Hussain Ejaz , Jahangir Sajid , Yousuf Sammer
Published: February 2014

In the title compound, C9H13N3O4, an ester of the anti-infection drug secnidazole, the dihedral angle between the nitroimidazole mean plane (r.m.s. deviation = 0.028 Å) and the pendant acetate group is 43.17 (11)°. In the crystal, inversion dimers linked by pairs of C—H...O interactions generateR22(10) loops and further C—H...O hydrogen bonds link the dimers into [100] chains. Weak aromatic π–π stacking interactions with a centroid–centroid distance of 3.7623 (11) Å are also observed.
2-Bromo-1-(1-phenylsulfonyl-1H-indol-3-yl)propan-1-one
Authors: Ramathilagam C. , Umarani P. R. , Saravanan V. , Mohanakrishnan A. K. , Gunasekaran B. , Manivannan V.
Published: February 2014

In the title compound, C17H14BrNO3S, the phenyl ring makes a dihedral angle of 89.78 (16)° with the plane of the indole ring system. The terminal Br atom and the methyl group are disordered over two sets of sites, with site occupancies of 0.860 (2) and 0.140 (2). In the crystal, molecules are linked into a chain along theb-axis direction by weak C—H...O hydrogen bonds. The chains are further linked by C—H...π interactions, forming layers parallel to thebcplane.