bluuebunny/crossref_metadata_2025 huggingface dataset:
Sec14-nodulin proteins and the patterning of phosphoinositide landmarks for developmental control of membrane morphogenesis
Authors: Ghosh Ratna , de Campos Marília K. F. , Huang Jin , Huh Seong K. , Orlowski Adam , Yang Yuan , Tripathi Ashutosh , Nile Aaron , Lee Hsin-Chieh , Dynowski Marek , Schäfer Helen , Róg Tomasz , Lete Marta G. , Ahyayauch Hasna , Alonso Alicia , Vattulainen Ilpo , Igumenova Tatyana I. , Schaaf Gabriel , Bankaitis Vytas A.
Published: March 2015

Polarized membrane morphogenesis is a fundamental activity of eukaryotic cells. This process is essential for the biology of cells and tissues, and its execution demands exquisite temporal coordination of functionally diverse membrane signaling reactions with high spatial resolution. Moreover, mechanisms must exist to establish and preserve such organization in the face of randomizing forces that would diffuse it. Here we identify the conserved AtSfh1 Sec14-nodulin protein as a novel effector of phosphoinositide signaling in the extreme polarized membrane growth program exhibited by growing Arabidopsis root hairs. The data are consistent with Sec14-nodulin proteins controlling the lateral organization of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) landmarks for polarized membrane morphogenesis in plants. This patterning activity requires both the PtdIns(4,5)P2 binding and homo-oligomerization activities of the AtSfh1 nodulin domain and is an essential aspect of the polarity signaling program in root hairs. Finally, the data suggest a general principle for how the phosphoinositide signaling landscape is physically bit mapped so that eukaryotic cells are able to convert a membrane surface into a high-definition lipid-signaling screen.
WS1: one more new Galactic bona fide luminous blue variable
Authors: Kniazev A. Y. , Gvaramadze V. V. , Berdnikov L. N.
Published: March 2015

In this Letter, we report the results of spectroscopic and photometric monitoring of the candidate luminous blue variable (LBV) WS1, which was discovered in 2011 through the detection of a mid-infrared circular shell and follow-up optical spectroscopy of its central star. Our monitoring showed that WS1 brightened in the B, V and I bands by more than 1 mag during the last three years, while its spectrum revealed dramatic changes during the same time period, indicating that the star became much cooler. The light curve of WS1 demonstrates that the brightness of this star has reached maximum in 2013 December and then starts to decline. These findings unambiguously proved the LBV nature of WS1 and added one more member to the class of Galactic bona fide LBVs, bringing their number to sixteen (an updated census of these objects is provided).
Anachronism
Authors: De Grazia Margreta
Published: March 2015

To an age enjoined to “Always Historicize,” anachronism is an embarrassment. It is not merely getting a date wrong, a chronological error. It is mistaking some aspect of a period’s regulative conceptualization of the world. It typically occurs when we impose our own modern conceptions onto the workings of the past. Sensitivity to anachronism and an understanding of history has generally been regarded as one of the defining features of the Renaissance, much to the detriment of the Medieval, that thereby becomes historically insensitive. This essay works to loosen our disciplinary commitment to chronology and periods by looking at other ways of relating to the past, beginning with a radical reconstrual of Lorenzo Valla’s exposure of the Donation of Constantine. It is not violations of chronology that Valla exposes but bad rhetoric. And it is from the arts of language that the essay hints at alternative ways of relating to the past, through narrative and figuration rather than numerical timelines and metaphysical periods.
Historiography
Authors: Lander Jesse
Published: March 2015

During the Reformation, arguments over the near and distant past are crucial for making people increasingly aware of the plurality of competing, even contradictory, accounts of the past. This article examines the way in which historical accounts of Richard III’s reign point to the emergence of a historiographical consciousness, an awareness that written history is partial in both senses of the word. It considers the extent of John Foxe’s influence on English history writing and how he made revisionist history mainstream. It analyses chronicle history plays, especially The True Tragedie of Richard III, as evidence that historiographical consciousness was widespread in the period. It also treats the connection between dissimulation and conspiracy in Thomas More’s History and cites George Buck’s The History of King Richard III(1619) as a remarkable example of revisionism that deploys historical learning against received opinion.
Literary Histories
Authors: Lerer Seth
Published: March 2015

Literary history has had a mixed history among the readers and the writers of the European traditions. For William Warburton, an eighteenth-century ecclesiast and critic, literary history was “the most agreeable subject in the world.” However, the early nineteenth-century German poet Heinrich Heine describes literary history as a “morgue where each seeks out the friend he most loved.” The complex connotation of literary history stems in part from the modern European understanding of the place of literature in the formation of national identity. This article examines how the history of medieval literature was received during the Renaissance. It first looks at the regulations of late Henrician reading, particularly the 1543 Act for the Advancement of True Religion, before focusing on Miles Hogarde and his poetry. It then discusses Richard Tottel’s Miscellany in the context of English literature and its past, along with the poetry of love and loss that follows Tottel.
Enclosed Spaces
Authors: Staley Lynn
Published: March 2015

Bede described Britain as a bountiful and beautiful island characterized by ethnic diversity, whereas Gildas viewed it as a fallen garden or bride. Bede and Gildas established the foundations of a nation whose boundaries enclosed people or peoples, a site of the struggles between individuals and of individuals. English historians from Gervase of Canterbury to Ralph of Diceto, William of Malmesbury, and William of Newburgh look at the history of Britain as a history instituted by Bede and Gildas, whose impulses to write geography as narrative are evident in the two most important histories of the later Middle Ages: Brut and Ranulf Higden’s Polychronicon. This article examines Britain as an enclosed space protected by the sea. It begins with an analysis of Andrew Marvell’s poem “Upon Appleton House” and locates Marvell within the company of those who wrote Britain’s history through its geography, particularly William Langland and Geoffrey Chaucer. It then describes the Wilton Diptych as an icon of sacred kingship and sacred geography.
The Eucharist
Authors: Aers David , Beckwith Sarah
Published: March 2015

This chapter explores theological and ethical dimensions of the Eucharist in the later Middle Ages and in the Reformation. The exploration introduces a number of genres and practices, because the Eucharist was a central and pervasive presence in Christian cultures, including those opposing medieval liturgy and teaching. One of the focal points of the study is the emergence of the doctrine and practice of transubstantiation, a language that became enshrined in thirteenth century orthodoxy. The chapter sets out with St. Augustine, who did not know either this doctrine, or the theological questions it sponsored (such as, what happens when a mouse eats the consecrated host), or its practice, together with its rich visionary accompaniments (such as bleeding hosts and manifestations of bleeding parts of the body of Christ or the Infant Jesus). After Augustine, a cluster of medieval writers and performances are addressed. The chapter concludes with commentary on the Reformation, and some rumination of Shakespeare, especially The Tempest.
Folly
Authors: Walker Greg
Published: March 2015

According to the chronicler Edward Hall, the execution of Sir Thomas More, who was sentenced to die on the gallows for refusing to acknowledge the Royal Supremacy, was characterized by a characteristically frivolous lack of decorum on the part of More himself, most notably on the scaffold itself. Both More’s evangelical opponents and his catholic allies noted his merry disposition. This article examines how the ideas of mirth and folly are woven through both More’s public career and the life of his close contemporary and nephew, the Catholic writer and playwright John Heywood. It considers the two men’s adoption and adaptation of classical and medieval notions of foolishness and comedy for their own ends in the dangerous years of Henry VIII’s Reformation. To understand More’s alleged lapse in judgment during his own execution and what this might suggest about the uses of mirth in pre-modern culture more generally, the article analyzes it in the context of his attitude towards theater and his Utopia as a satire for and of humanists.
Passion
Authors: Targoff Ramie
Published: March 2015

During the Renaissance, erotic love emerged as a favorite theme of Italian intellectuals. From the Neoplatonic treatises of Marsilio Ficino and Pico della Mirandola, to the works of Petrarch and Dante, the paintings of Botticelli and Raphael, the trattati d’amore (treatises of love) by Pietro Bembo and Leone Ebreo, the learned commentaries on the sonnets of Michelangelo and Lorenzo de Medici, or the medical writings on lovesickness, Italy’s obsession with the subject of love was evident. Italian poets such as Dante were particularly preoccupied with the female beloved, whom they typically idealized as a kind of angelic lady (donna angelicata), a heavenly character, rather than an object of sensual appetite and affection. Thomas Wyatt translated Petrarch’s sonnets, including Rime Sparse, by stripping from them one of their most fundamental features: the idea that erotic love could transcend the beloved’s death. This article examines Wyatt’s erotic poetry, how his Protestantism influenced his translations of Petrarchan lyrics, and his attitude toward Neoplatonism.
Metamemory and Affect
Authors: Efklides Anastasia
Published: March 2015

Research in the last decade has produced growing evidence on relations of metamemory with affect, particularly in a self-regulation framework. The chapter presents an overview of empirical evidence suggesting that (a) affect (e.g., mood, stimulus emotionality) can have an impact on metamemory, and particularly on metacognitive experiences such as feeling of difficulty, mental effort, or confidence; (b) metacognitive experiences can have an impact on affect (e.g., feeling of not knowing can trigger curiosity); and (c) cognitive events or states (e.g., interruption) can trigger both affective and metacognitive responses, such as surprise and feeling of difficulty. The mechanism underlying the interrelations between metamemory and affect involves, besides fluency/disfluency and related experiences, metacognitive knowledge (including remembered utility) and self-concept. The theoretical implications of empirical findings on the interrelations between metamemory and affect are discussed and challenges for future research on metamemory pointed out.
Poised in the Creative Now
Authors: Guerrero Nina , Marcus David , Turry Alan
Published: March 2015

Nordoff-Robbins music therapy was founded through the pioneering collaboration between Paul Nordoff (1909–1977), an accomplished composer and pianist, and Clive Robbins (1927–2011), an innovative special educator. Their partnership began in 1959 at Sunfield Children’s Homes in Worcestershire, England, and they worked together for approximately 16 years in Europe and the United States. In 1975, formal training began at the newly opened Nordoff-Robbins Music Therapy Centre in London. In the same year, Clive Robbins formed a new music therapy team with his wife Carol Robbins (1942–1996). The Robbins’ developed and disseminated the Nordoff-Robbins model, and in 1990 they established the Nordoff-Robbins Center for Music Therapy at New York University’s Steinhardt School of Culture, Education, and Human Development. Throughout its history, the clinical techniques, training methods, and research within this model have been based in close engagement with clinical work.
Information Structure and Presupposition
Authors: Sæbø Kjell Johan
Published: March 2015

This article surveys and discusses the core points of contact between notions of information structure and notions of presupposition. Section 1 is devoted to the ‘weak’ presuppositional semantics for focus developed by Mats Rooth, describing its properties with regard to verification and accommodation and showing that it can successfully account for a wide range of phenomena. Section 2 examines the stronger thesis that focus–background structures give rise to existential presuppositions, and finds the counterarguments that have been raised to carry considerable weight. Section 3 looks into the relationship between Givenness and run-of-the-mill presuppositions, finding that this relationship is looser than might be expected, mainly because a presupposition may be in need of focus marking instead of givenness marking.
Discourse Functions
Authors: Kiss Katalin É.
Published: March 2015

The chapter first summarizes the syntactic, semantic, and pragmatic properties of the topic–comment structure in the Hungarian sentence. It describes the topic as a constituent external to the extended verbal projection, binding an empty argument in the comment, derived by topic movement or base-generated in situ. The topic functions as the logical subject of predication. Then the chapter discusses the focus–background articulation of the comment. The Hungarian sentence structure contains a designated focus position at the left edge of the comment. The focus elicits verb movement. The Hungarian focus construction, expressing exhaustive identification, is analysed as a predication structure both syntactically and semantically. It is claimed to represent specificational predication, with the background determining a set, and the focus referentially identifying its members.
Youth and Interfaith Conflict Transformation
Authors: Patel Eboo , Meyer Cassie
Published: March 2015

This chapter explores “interfaith leadership,” a framework for religious peacebuilding across lines of religious diversity. Drawing on the example of Martin Luther King Jr., it articulates a constructive theory of interfaith leadership and reflects on its application, particularly in the current climate of religious diversity within the United States. The chapter considers the possibility of a movement or critical mass of individuals committed to building “religious pluralism,” and focuses on young people as potential agents of such social change. The authors write from their location as interfaith practitioners, working for the Chicago-based nonprofit Interfaith Youth Core, which focuses on building religious pluralism on American college and university campuses; here they seek to put this work in conversation with relevant peacebuilding literature.
Hume on Is and Ought
Authors: Pigden Charles
Published: March 2015

Hume contends that you can’t get an ought from an is. Searle professed to prove otherwise, deriving a conclusion about obligations from premises about promises. Since can’t derive a substantive ought from an is by logic alone, Searle is best construed as claiming that there are analytic bridge principles linking premises about promises to conclusions about obligations. But we can no more derive a moral obligation to pay up from the fact that a promise has been made than we can derive a duty to fight a duel from the fact that a challenge has been issued—just conclusions about what we ought to do according to the rules of the relevant games. Hume suggests bridge principles that would take us from the rules of the games to conclusions about duties, but these are distinctly dubious. The argument features an obtreperous earl, an anarchist philosopher and a dueling Prime Minister.
Freedom of the Press
Authors: Graber Doris A.
Published: March 2015

Freedom of the press has become a popular idea throughout the world. The promise of free expression, however, is not necessarily realized when governments feel that security and stability are threatened. This chapter explains the concept of freedom of the press. The theories and assumptions about freedom of the press, balancing conflicting rights, and societal constraints are reviewed. The chapter then shows how that concept is implemented, discussing legal, political, and economic factors for evaluation. The environmental factors are compared, and the reason behind press freedom violations by governments is discussed. Questions for the future of research on freedom of the press are offered.
Becoming Israel in the Wilderness of Numbers
Authors: Leveen Adriane
Published: March 2015

Numbers describes the building of an Israelite collective in the wilderness. A fledgling people struggle mightily to form themselves into a unity but are overcome by their own complaints, desires for a past they leave behind in Egypt and doubts of their ability to conquer the promised land. Several stories highlight the dramatic pressures both internal (how they saw themselves) and external (how they imagined others saw them) that influence the successes and failures of a unified Israel. Yet the self-critique embedded in the tale of the journey leads a new generation to replace dissatisfaction and dissent with a shared determination. A tale of struggles overcome gives the children of Israel a chance to reach for a different future, imagined but not yet fulfilled.
Silicon-Induced Systemic Defense Responses in Perennial Ryegrass Against Infection by Magnaporthe oryzae
Authors: Rahman Alamgir , Wallis Christopher M. , Uddin Wakar
Published: March 2015

Sustainable integrated disease management for gray leaf spot of perennial ryegrass may involve use of plant defense elicitors with compatible traditional fungicides to reduce disease incidence and severity. Silicon (Si) has previously been identified as a potential inducer or modulator of plant defenses against different fungal pathogens. To this end, perennial ryegrass was inoculated with the causal agent of gray leaf spot, Magnaporthe oryzae, when grown in soil that was nonamended or amended with three different levels of calcium silicate (1, 5, or 10 metric tons [t]/ha). When applied at a rate of 5 t/ha, calcium silicate was found to significantly suppress gray leaf spot in perennial ryegrass, including a significant reduction of disease incidence (39.5%) and disease severity (47.3%). Additional studies observed nonpenetrated papillae or cell-wall appositions harboring callose, phenolic autofluorogens, and lignin-associated polyphenolic compounds in grass grown in the Si-amended soil. Regarding defense-associated enzyme levels, only following infection did grass grown in Si-amended soil exhibit greater activities of peroxidase and polyphenol oxidase than equivalent inoculated control plants. Also following infection with M. oryzae, grass levels of several phenolic acids, including chlorogenic acid and flavonoids, and relative expression levels of genes encoding phenylalanine ammonia lyase (PALa and PALb) and lipoxygenase (LOXa) significantly increased in Si-amended plants compared with that of nonamended control plants. These results suggest that Si-mediated increase of host defense responses to fungal pathogens in perennial ryegrass has a great potential to be part of an effective integrated disease management strategy against gray leaf spot development.
Body mass estimates of an exceptionally completeStegosaurus(Ornithischia: Thyreophora): comparing volumetric and linear bivariate mass estimation methods
Authors: Brassey Charlotte A. , Maidment Susannah C. R. , Barrett Paul M.
Published: March 2015

Body mass is a key biological variable, but difficult to assess from fossils. Various techniques exist for estimating body mass from skeletal parameters, but few studies have compared outputs from different methods. Here, we apply several mass estimation methods to an exceptionally complete skeleton of the dinosaurStegosaurus. Applying a volumetric convex-hulling technique to a digital model ofStegosaurus, we estimate a mass of 1560 kg (95% prediction interval 1082–2256 kg) for this individual. By contrast, bivariate equations based on limb dimensions predict values between 2355 and 3751 kg and require implausible amounts of soft tissue and/or high body densities. When corrected for ontogenetic scaling, however, volumetric and linear equations are brought into close agreement. Our results raise concerns regarding the application of predictive equations to extinct taxa with no living analogues in terms of overall morphology and highlight the sensitivity of bivariate predictive equations to the ontogenetic status of the specimen. We emphasize the significance of rare, complete fossil skeletons in validating widely applied mass estimation equations based on incomplete skeletal material and stress the importance of accurately determining specimen age prior to further analyses.
Reproductive interference explains persistence of aggression between species
Authors: Drury Jonathan P. , Okamoto Kenichi W. , Anderson Christopher N. , Grether Gregory F.
Published: March 2015

Interspecific territoriality occurs when individuals of different species fight over space, and may arise spontaneously when populations of closely related territorial species first come into contact. But defence of space is costly, and unless the benefits of excluding heterospecifics exceed the costs, natural selection should favour divergence in competitor recognition until the species no longer interact aggressively. Ordinarily males of different species do not compete for mates, but when males cannot distinguish females of sympatric species, females may effectively become a shared resource. We model how reproductive interference caused by undiscriminating males can prevent interspecific divergence, or even cause convergence, in traits used to recognize competitors. We then test the model in a genus of visually orienting insects and show that, as predicted by the model, differences between species pairs in the level of reproductive interference, which is causally related to species differences in female coloration, are strongly predictive of the current level of interspecific aggression. Interspecific reproductive interference is very common and we discuss how it may account for the persistence of interspecific aggression in many taxonomic groups.
Broad supernatural punishment but not moralizing high gods precede the evolution of political complexity in Austronesia
Authors: Watts Joseph , Greenhill Simon J. , Atkinson Quentin D. , Currie Thomas E. , Bulbulia Joseph , Gray Russell D.
Published: March 2015

Supernatural belief presents an explanatory challenge to evolutionary theorists—it is both costly and prevalent. One influential functional explanation claims that the imagined threat of supernatural punishment can suppress selfishness and enhance cooperation. Specifically, morally concerned supreme deities or ‘moralizing high gods' have been argued to reduce free-riding in large social groups, enabling believers to build the kind of complex societies that define modern humanity. Previous cross-cultural studies claiming to support the MHG hypothesis rely on correlational analyses only and do not correct for the statistical non-independence of sampled cultures. Here we use a Bayesian phylogenetic approach with a sample of 96 Austronesian cultures to test the MHG hypothesis as well as an alternative supernatural punishment hypothesis that allows punishment by a broad range of moralizing agents. We find evidence that broad supernatural punishment drives political complexity, whereas MHGs follow political complexity. We suggest that the concept of MHGs diffused as part of a suite of traits arising from cultural exchange between complex societies. Our results show the power of phylogenetic methods to address long-standing debates about the origins and functions of religion in human society.
Evolution of hosts paying manifold costs of defence
Authors: Cressler Clayton E. , Graham Andrea L. , Day Troy
Published: March 2015

Hosts are expected to incur several physiological costs in defending against parasites. These include constitutive energetic (or other resource) costs of a defence system, facultative resource costs of deploying defences when parasites strike, and immunopathological costs of collateral damage. Here, we investigate the evolution of host recovery rates, varying the source and magnitude of immune costs. In line with previous work, we find that hosts paying facultative resource costs evolve faster recovery rates than hosts paying constitutive costs. However, recovery rate is more sensitive to changes in facultative costs, potentially explaining why constitutive costs are hard to detect empirically. Moreover, we find that immunopathology costs which increase with recovery rate can erode the benefits of defence, promoting chronicity of infection. Immunopathology can also lead to hosts evolving low recovery rate in response to virulent parasites. Furthermore, when immunopathology reduces fecundity as recovery rate increases (e.g. as for T-cell responses to urogenital chlamydiosis), then recovery and reproductive rates do not covary as predicted in eco-immunology. These results suggest that immunopathological and resource costs have qualitatively different effects on host evolution and that embracing the complexity of immune costs may be essential for explaining variability in immune defence in nature.
Sensitivity analysis of Wntβ-catenin based transcription complex might bolster power-logarithmic psychophysical law & reveal preserved gene gene interactions
Authors: Sinha Shriprakash
Published: March 2015

Recently, psychophysical laws have been observed to be functional in certain factors working downstream of the Wnt pathway. This work tests the veracity of the prevalence of such laws, albeit at a coarse level, using sensitivity analysis on biologically inspired epigenetically influenced computational causal models. In this work, the variation in the effect of the predictive behaviour of the transcription complex (TRCMPLX) conditional on the evidences of gene expressions in normal/tumor samples is observed by varying the initially assigned values of conditional probability tables (cpt) for TRCMPLX. Preliminary analysis shows that the variation in predictive behaviour of TRCMPLX follows power-logarithmic psychophysical law, crudely. More recently, wet lab experiments have proved the existence of sensors that behave in a logarithmic fashion thus supporting the earlier proposed postulates based on computational sensitivity analysis of this manuscript regarding the existence of logarithmic behaviour in the signaling pathways. It also signifies the importance of systems biology approach where in silico experiments combined with in vivo/in vitro experiments have the power to explore the deeper mechanisms of a signaling pathway. Additionally, it is hypothesized that these laws are prevalent at gene-gene interaction level also. The interactions were obtained by thresholding the inferred conditional probabilities of a gene activation given the status of another gene activation. The deviation in the interactions in normal/tumor samples was similarly observed by varying the initially assigned values of conditional probability tables (cpt) for TRCMPLX. Analysis of deviation in interactions show prevalence of psychophysical laws and is reported for interaction between elements of pairs (SFRP3, MYC), (SFRP2, CD44) and (DKK1, DACT2). Based on crude static models, it is assumed that dynamic models of Bayesian networks might reveal the phenomena in a better way.
A pan-cancer catalogue of driver protein interaction interfaces
Authors: Porta-Pardo Eduard , Hrabe Thomas , Godzik Adam
Published: March 2015

Despite their critical importance in maintaining the integrity of all cellular pathways, the specific role of mutations on protein-protein interaction (PPI) interfaces as cancer drivers, though known for some specific examples, has not been systematically studied. We analyzed missense somatic mutations in a pan-cancer cohort of 5,989 tumors from 23 projects of The Cancer Genome Atlas (TCGA) for enrichment on PPI interfaces using e-Driver, an algorithm to analyze the mutation pattern of specific protein regions such as PPI interfaces. We identified 128 PPI interfaces enriched in somatic cancer mutations. Our results support the notion that many mutations in well-established cancer driver genes, particularly those in critical network positions, act by altering PPI interfaces. Finally, focusing on individual interfaces we are also able to show how tumors driven by the same gene can have different behaviors, including patient outcomes, depending on whether specific interfaces are mutated or not.
Identification of novel transcriptional regulators of PKA subunits inSaccharomyces cerevisiaeby Quantitative Promoter–Reporter Screening
Authors: Pautasso C , Chatfield-Reed K , Chua G , Zaremberg V , Rossi S
Published: March 2015

The cAMP dependent protein kinase (PKA) signaling is a broad specificity pathway that plays important roles in the transduction of environmental signals triggering precise physiological responses. cAMP-signal transduction specificity is achieved and controlled at several levels. TheSaccharomyces cereviciaePKA holoenzyme consists of two catalytic subunits encoded byTPK1,TPK2andTPK3genes, and two regulatory subunits encoded byBCY1gene. In this work we studied the activity of these gene promoters using a reporter-synthetic genetic array screen, with the goal of identifying novel regulators of PKA subunits expression. Gene ontology (GO) analysis of the regulators identified showed that these regulators were enriched for annotations associated with roles in several GO biological process, as lipid and phosphate metabolism or transcription regulation and regulate all or some of the four promoters. Further characterization of the effect of these pathways on promoter activity and mRNA levels pointed to inositol, inositol polyphosphates, choline and phosphate as novel upstream signals that regulate transcription of PKA subunit genes. In addition, within each category there are genes that regulate only one of the promoters and genes that regulate more than one of them at the same time. These results support the role of transcription regulation of each PKA subunit in cAMP specificity signaling. Interestingly, many of the known targets of PKA phosphorylation are associated with the identified pathways, opening the possibility of a reciprocal regulation in which PKA would be coordinating different metabolic pathways and these processes would in turn, regulate expression of the kinase subunits.
Selection and explosive growth may hamper the performance of rare variant association tests
Authors: Uricchio Lawrence H. , Witte John S. , Hernandez Ryan D.
Published: March 2015

Much recent debate has focused on the role of rare variants in complex phenotypes. However, it is well known that rare alleles can only contribute a substantial proportion of the phenotypic variance when they have much larger effect sizes than common variants, which is most easily explained by natural selection constraining trait-altering alleles to low frequency. It is also plausible that demographic events will influence the genetic architecture of complex traits. Unfortunately, most rare variant association tests do not explicitly model natural selection or non-equilibrium demography. Here, we develop a novel evolutionary model of complex traits. We perform numerical calculations and simulate phenotypes under this model using inferred human demographic and selection parameters. We show that rare variants only contribute substantially to complex traits under very strong assumptions about the relationship between effect size and selection strength. We then assess the performance of state-of-the-art rare variant tests using our simulations across a broad range of model parameters. Counterintuitively, we find that statistical power is lowest when rare variants make the greatest contribution to the additive variance, and that power is substantially lower under our model than previously studied models. While many empirical studies have attempted to identify causal loci using rare variant association methods, few have reported novel associations. Some authors have interpreted this to mean that rare variants contribute little to heritability, but our results show that an alternative explanation is that rare variant tests have less power than previously estimated.
Lobbying on the integrated reporting framework
Authors: Reuter Marek , Messner Martin
Published: March 2015

Purpose

– The purpose of this paper is to examine formal participation in the early phase of the International Integrated Reporting Council’s (IIRC’s) standard-setting. The objective of the paper is to shed light on the characteristics of lobbying parties and the determinants of their lobbying behavior toward the IIRC. Additionally, the most important points of contestation regarding the IIRC’s initial proposal for integrated reporting are identified and discussed.

Design/methodology/approach

– The authors analyze comment letters issued toward the IIRC’s 2011 discussion paper on the basis of a content analysis. The analysis is guided mainly by Sutton’s (1984) rational-choice model of lobbying and by findings from extant financial accounting lobbying research. The analysis of the data is both quantitative and qualitative.

Findings

– The paper improves the understanding of the political nature of standard-setting in the context of integrated reporting. Among other things, the authors find that comment letters toward the IIRC’s discussion paper are mainly written by large multinational firms (as opposed to small- and medium-sized ones) and by preparers (as opposed to users). The authors also observe active lobbying by sustainability service firms and professional bodies which tend to take a critical position vis-à-vis the discussion paper’s emphasis on investor needs and shareholder value creation. Moreover, the qualitative analysis reveals that respondents voice different concerns regarding, for instance, the scope of audience of integrated reporting, issues of materiality and the relationship between integrated reporting and other existing reporting frameworks.

Research limitations/implications

– The analysis is limited to a consideration of the 2011 discussion paper of the IIRC. The IIRC’s more recent and forthcoming proposals will likely provide a basis to extend the paper’s findings and allow investigation of the role of lobbying for the further development of the framework.

Originality/value

– The paper is, to the best of the knowledge, the first one to explore lobbying behavior by means of comment letters in the context of integrated reporting.
A day in the life of a Peer Support Worker: One of those make or break visits
Authors: Watson Emma
Published: March 2015

Purpose

– The purpose of this paper is to describe the experience of being a peer support worker (PSW).

Design/methodology/approach

– Narrative account of a one to one meeting with a peer written from the perspective of a PSW.

Findings

– Key reflections centre on the importance of establishing and maintaining boundaries, the role of trust, and a different understanding of what constitutes risk.

Originality/value

– While there is a great deal written about the theory of peer support work, little is published about PSWs experience. This paper provides important insights into the nature of peer support work.
Real lives: promoting recovery through personalisation and peer support
Authors: Perkins Rachel , Atkins Julie , Hunter Nicole , Repper Poppy , Robertson Peter David , Thornton Phoebe , Thornton Sue
Published: March 2015

Purpose

– The purpose of this paper is to describe the development of Real Lives: a community interest company that provides peer support for people who face significant mental health challenges using personal budgets.

Design/methodology/approach

– The paper offers a descriptive summary of the vision behind Real Lives and the successful realisation of this vision in practice based on interviews by the first author with the directors, Operational Manager, Cafe Manager and “Peers and Allies for in Living” who provide support to clients.

Findings

– The successful development of Real Lives shows that it is possible to utilise peer support and personal budgets to a create small, values based, financially viable organisation outside the statutory sector that is part of its community and can provide outside the statutory sector. A service for people facing significant mental health challenges that is personalised, recovery-focused and puts the client in control and is focused on helping them to do the things they want to do and pursue their aspirations.

Originality/value

– Real Lives is an innovative recovery-focused service that is part of its community and offers a model for utilising Self-Directed Support and personal budgets and that might be replicated by others.
Remarkable lives: Spencer Insley in conversation with Jerome Carson
Authors: Insley Spencer , Carson Jerome
Published: March 2015

Purpose

– The purpose of this paper is to provide a profile of Spencer Insley.

Design/methodology/approach

– Spencer gives a short biographical account and is then interviewed by Jerome. Areas covered in the narrative are the misery of mental illness, the prodromal signs of illness, hospital admission and discharge to supported accommodation.

Findings

– Apart from the losses resulting from a diagnosis of major mental disorder, Spencer also talks about the loss of friendships. His admission to hospital was especially traumatic, leaving him frightened and confused and feeling he was treated like an animal.

Research limitations/implications

– While Spencer's is only one story of many, his experiences have a sorry familiarity to them.

Practical implications

– Too long denied in the history of psychiatry, service user narratives help us understand the nature of mental suffering and the often inadequate nature of service responses to mental distress.

Social implications

– Involuntary admissions to hospital need to be handled in a more therapeutic manner.

Originality/value

– So often it is nurses and occupational therapists who have the most impact on the lives of those with lived experience. Psychiatrists were felt not to be interested in Spencer, whereas his community mental health nurse “Had a genuine interest in what I was doing and how I was getting along”.
How does enforcement of smoke free grounds in acute mental health settings sit with “recovery” focused practice? A personal view
Authors: Hurley Di
Published: March 2015

Purpose

– The purpose of this paper is to outline, from the perspective of someone involved in smoking cessation, concerns about the intention to make all hospital grounds “smoke free”.

Design/methodology/approach

– This paper takes the form of a narrative account.

Findings

– Reflective account offering a personal point of view – no findings presented.

Originality/value

– An important viewpoint relating to an issue of great concern to many people working in and using mental health services.
Malassezia species and their associated skin diseases
Authors: Harada Kazutoshi , Saito Mami , Sugita Takashi , Tsuboi Ryoji
Published: March 2015

Malassezia spp. are lipophilic fungi that occur on all skin surfaces of humans and animals as commensal and pathogenic organisms. In the 2000s, several new species were added to the Malassezia genus by Japanese researchers. The genus Malassezia now includes 14 species of basidiomycetous yeast. Culture‐independent molecular analysis clearly demonstrated that the DNA of Malassezia spp. was predominantly detected in core body and arm sites, suggesting that they are the dominant fungal flora of the human body. Malassezia spp. have been implicated in skin diseases including pityriasis versicolor (PV), Malassezia folliculitis (MF), seborrheic dermatitis (SD) and atopic dermatitis (AD). While Malassezia spp. are directly responsible for the infectious diseases, PV and MF, they act as an exacerbating factor in AD and SD. The fatty acids generated by Malassezia lipase can induce inflammation of the skin, resulting in development of SD. Patch and serum immunoglobulin E tests revealed that AD patients were hypersensitive to Malassezia. However, these findings only partially elucidated the mechanism by which Malassezia spp. induce inflammation in the skin; understanding of the pathogenetic role of Malassezia spp. in SD or AD remains incomplete. In this article, the latest findings of Malassezia research are reviewed with special attention to skin diseases.
Immunoresponses in dermatomycoses
Authors: Hau Carren Sy , Tada Yayoi , Kanda Naoko , Watanabe Shinichi
Published: March 2015

Contact with fungal pathogens initiates a series of host responses beginning with innate immunity, which leads to fungal recognition and microbial killing. The innate immune system also modulates the adaptive immune responses, leading to the establishment of immunological memory and protection against pathogens. In the case of dimorphic fungi such as Candida albicans and Malassezia, the immune system plays an important role in tolerance and resistance when managing the organisms either as commensal microbiota or invading pathogens, and disruption of this balance can result in pathological consequences for the host. In addition, Malassezia and dermatophytes have immunomodulatory capabilities that allow them to adapt to their environments and they may exert different effects in healthy and diseased skin. Here, we discuss the host immune responses to dermatomycoses caused by dimorphic fungi such as C. albicans and Malassezia as well as dermatophytes such as Trichophyton spp. and Arthroderma benhamiae to gain a better understanding of the mechanisms of the host–dermatomycosis interaction.
Simulated microgravity promotes monocyte adhesion to rat aortic endothelium via nuclear factor‐κB activation
Authors: Liu Huan , Wang Zhong‐Chao , Bai Yun‐Gang , Cai Yue , Yu Jin‐Wen , Zhang Hai‐Jun , Bao Jun‐Xiang , Ren Xin‐Ling , Xie Man‐Jiang , Ma Jin
Published: March 2015

Microgravity‐induced vascular remodelling may play an important role in post‐spaceflight orthostatic intolerance. In this study, we aimed to investigate the effects of simulated microgravity on monocyte adhesion to aortic endothelium in hindlimb unweighted rats and to elucidate the underlying mechanisms associated with this event. Sprague–Dawley rats were subjected to 4‐week hindlimb unweighting to simulate microgravity. The recruitment of monocytes to the abdominal aorta was investigated by en face immunofluorescence staining and monocyte binding assays. The expression of the adhesion molecules E‐selectin and vascular cell adhesion molecule‐1 as well as the cytokine monocyte chemoattractant protein (MCP)‐1 was evaluated by immunohistochemical staining, western blot, and quantitative reverse transcription polymerase chain reaction analyses. Additionally, nuclear factor‐κB (NF‐κB) activation and the messenger RNA expression levels of E‐selectin, vascular cell adhesion molecule‐1, and MCP‐1 were assessed with the administration of an NF‐κB inhibitor, pyrrolidine dithiocarbamate. Results showed that simulated microgravity significantly increased monocyte recruitment to the aortic endothelium, protein expression of E‐selectin and MCP‐1, and NF‐κB activation in the abdominal aorta of rats. Pyrrolidine dithiocarbamate treatment not only significantly inhibited NF‐κB activity but also reduced the messenger RNA levels of E‐selectin, vascular cell adhesion molecule‐1, and MCP‐1 as well as monocyte recruitment in the abdominal aorta of hindlimb unweighted rats. These results suggest that simulated microgravity increases monocyte adhesion to rat aortic endothelium via the NF‐κB‐mediated expression of the adhesion molecule E‐selectin and the cytokine MCP‐1. Therefore, an NF‐κB‐mediated inflammatory response may be one of the cellular mechanisms responsible for arterial remodelling during exposure to microgravity.
Curcumin ameliorates asthmatic airway inflammation by activating nuclear factor‐E2‐related factor 2/haem oxygenase (HO)‐1 signalling pathway
Authors: Liu Liyun , Shang Yunxiao , Li Miao , Han Xiaohua , Wang Jia , Wang Juan
Published: March 2015

Previous studies have shown that curcumin alleviates asthma in vivo. However, the relationship between curcumin and the nuclear factor‐E2‐related factor 2 (Nrf2)/haem oxygenase (HO)‐1 pathway in asthma treatment remains unknown. The aim of the present study was to investigate the mechanisms of curcumin involved in the amelioration of airway inflammation in a mouse asthma model. Curcumin was administrated to asthmatic mice, and bronchoalveolar lavage fluid was collected. Inflammatory cell infiltration was measured by Giemsa staining. Immunoglobulin E production in bronchoalveolar lavage fluid was measured by enzyme–linked immunosorbent assay. Histological analyses were evaluated with haematoxylin‐eosin and periodic acid‐Schiff staining. Airway hyperresponsiveness was examined by whole‐body plethysmography. Nuclear factor‐E2‐related factor 2, HO‐1, nuclear factor‐κB and inhibitory κB/p‐inhibitory κB levels in lung tissues were detected by western blot, and Nrf2 activity was measured by electrophoretic mobility shift assay. Tumour necrosis factor‐α, interleukin (IL)‐1β, and IL‐6 levels in the small interfering RNA‐transfected cells were detected by enzyme–linked immunosorbent assay. Curcumin treatment significantly reduced immunoglobulin E production, attenuated inflammatory cell accumulation and goblet cell hyperplasia, and ameliorated mucus secretion and airway hyperresponsiveness. Nuclear factor‐E2‐related factor 2 and HO‐1 levels in lung tissues were significantly increased. Meanwhile, Nrf2 activity was enhanced. Nuclear factor‐κB and p‐inhibitory κB levels were elevated in the lung tissue of ovalbumin‐challenged mice. Both were restored to normal levels after curcumin treatment. Haem oxygenase‐1 and nuclear Nrf2 levels were enhanced in dose‐ and time‐dependent manners in curcumin‐treated RAW264.7 cells. Curcumin blocked lipopolysaccharide‐upregulated expression of tumour necrosis factor‐α, IL‐1β, and IL‐6. After the cells were transfected with HO‐1 or Nrf2 small interfering RNA, lipopolysaccharide‐induced pro‐inflammation cytokine expression was significantly restored. In summary, curcumin might alleviate airway inflammation in asthma through the Nrf2/HO‐1 pathway, potentially making it an effective drug in asthma treatment.