bluuebunny/crossref_metadata_2025 huggingface dataset:
Falsafa and Law
Authors: March Andrew
Published: March 2016

This article examines the place of law in the falsafa (philosophy) tradition. Political philosophy was largely a derivative topic for the philosophers of the Islamic world. One indication of this is that the falsafa tradition did not produce a coherent philosophy of law that would concern itself with the meaning, essence, source, and forms of “law”: as such. This article looks at several philosophers in the Islamic tradition who are associated with political philosophy, including Abu Nasr al-Farabi and Ibn Sina, with particular emphasis on their view that the highest form of human existence consists in intellectual and spiritual perfection. It also considers the views of Ibn Bajja, Ibn Tufayl, and Ibn Rushd.
Computational Pragmatics
Authors: Bunt Harry
Published: March 2016

This chapter presents a characterisation of the field of computational pragmatics, discusses some of the fundamental issues in the field, and provides a survey of recent developments. Central to computational pragmatics is the development and use of computational tools and models for studying the relations between utterances and their context of use. Essential for understanding these relations are the use of inference and the description of language use as actions inspired by the context, and intended to influence the context. The chapter therefore focuses on recent work in the use of inference for utterance interpretation and in dialogue modeling in terms of dialogue acts, viewed as context-changing actions. The chapter concludes with a survey of recent activities concerning the construction and use of resources in computational pragmatics, in particular annotation schemes, annotated corpora, and tools for corpus construction and use.
Speech Acts
Authors: Levinson Stephen C.
Published: March 2016

The essential insight of speech act theory was that when we use language, we perform actions—in a more modern parlance, core language use in interaction is a form of joint action. Over the last thirty years, speech acts have been relatively neglected in linguistic pragmatics, although important work has been done especially in conversation analysis. Here we review the core issues—the identifying characteristics, the degree of universality, the problem of multiple functions, and the puzzle of speech act recognition. Special attention is drawn to the role of conversation structure, probabilistic linguistic cues, and plan or sequence inference in speech act recognition, and to the centrality of deep recursive structures in sequences of speech acts in conversation.
Client, Therapist, and Treatment Variables
Authors: Kimpara Satoko , Holt Hannah , Alsante Julianne , Beutler Larry E.
Published: March 2016

Consideration of the client–therapist match as a contributor, predictor, and optimizer of therapeutic change is not new in the behavioral health field. Indeed, it has evolved from two interactive and co-acting histories: (a) changing practices in psychotherapy research and (b) corresponding changes in the way that clinicians have viewed the role of theory in their practices. In the past three and a half decades, research emphasis has changed to increasingly reflect the roles played by client diagnoses, brands of interventions, and the theories that underlie their use. This chapter reviews the history of psychotherapy research and randomized controlled trials (RCTs). It then describes a contemporary view of RCT design that attempts to incorporate contemporary research developments that are bringing together research and practice.
Evaluating Treatments and Interventions
Authors: Jobe-Shields Lisa , Costello Amanda , Jackson Carrie , Hanson Rochelle F.
Published: March 2016

This chapter provides an overview of the evidence-based treatment (EBT) paradigm, beginning with definitional issues, followed by a discussion on use of the iterative process and the importance of strong academic–practice partnerships to inform the development, selection, and implementation of EBTs. The discussion then turns to the importance of attaining, measuring, and sustaining fidelity to the treatment models; and identifying common barriers to sustained EBT use. Drawing from our expertise related to interventions for children and adolescents, a few dissemination/implementation models are highlighted as examples of current efforts to achieve sustained use of EBTs among practitioners, within agencies, and across communities. This involves keeping up to date with the research and integrating the available evidence base with clinical expertise and patient characteristics, including cultural considerations and client preferences for treatment. The chapter concludes with directions for the future, including considerations for practitioners, referring agents, and agency senior leaders to promote, support, and sustain EBTs.
Dose Response and the Shape of Change
Authors: Nielsen Stevan Lars , Bailey Russell J. , Nielsen Dianne , Pedersen Tyler R.
Published: March 2016

Decades of research have demonstrated that psychotherapy is generally effective: symptoms change for the better and most clients feel and perform better after talk therapy (Lambert, 2013). In this chapter, we examine the relationship between number of therapy sessions and symptom change. We will focus on the primary claims of the two competing views of this relationship. The dose–effect (DE) model proposes that sessions are like doses; more session-doses cause more improvement. The good-enough-improvement (GEI) model proposes that clients persist in therapy until they improve enough to meet their goals; symptom change controls session attendance. We compare these competing models by examining patterns in the treatment we have provided at our counseling center. Our primary goal was to answer what we consider the most important question about session totals and symptom change: Do session totals cause symptom change, as proposed by the DE model, or is the reverse true: does symptom change control session totals, as proposed by the GEI model? At our counseling center both models fit the data. Greater session totals are associated with more improvement for some clients and other clients leave treatment when they improve enough to meet their treatment goals.
A Multidisciplinary, Biopsychosocial Approach to Treatment
Authors: Maltzman Sara
Published: March 2016

This concluding chapter of theOxford Handbook of Treatment Processes and Outcomes in Psychologydescribes the importance of breaking down research and practice silos in favor of a multidisciplinary and biopsychosocial approach regarding human physical and mental health. The chapter summarizes why we can have more confidence in treatments and interventions that “fit” within the context of converging lines of evidence across these multilevel systems. What multidisciplinary research tells us is that treatmentdoesmatter, as evidenced by multiple lines of research in animal models, particularly in fear-based and anxiety disorders. This research affirms that psychological/behavioral treatments are active and not reducible to nonspecific placebo effects. However, data indicate that placebo may prove valuable as a deliberately applied adjunct to psychological/behavioral and pharmacological treatments. Individual differences in self-regulation and temperament; genetic and epigenetic factors that influence resilience or maladaptive responses to adverse conditions; the buffering effects of social support; and how these factors may influence treatment process and outcomes are reviewed. Research evaluating pharmacological adjuncts to psychological/behavioral treatment underscores the complexity of delivering optimal treatment. Newer methodologies, such as neuroimaging, will assist in explicating the above complex interrelationships. This chapter also calls attention to research evaluating treatment outcomes, including dose response relationships and the importance of evaluating the therapist’s unique contribution to outcomes.
Treating the Child and Adolescent in the Family and Social Context
Authors: Lochman John E. , Powell Nicole , Boxmeyer Caroline , Sallee Meghan L. , Dillon Casey , Powe Cameron
Published: March 2016

Conduct problems and depression are two commonly occurring mental health problems affecting youth. For both conduct problems and depression, risk factors in the family, peer, and school contexts can contribute to the development and maintenance of these disorders in young people. Addressing contextual risk factors can lead to improvements in conduct problems and symptoms of depression. This chapter provides an overview of contextual risk factors for conduct problems and depression, and it reviews several effective interventions for treating each disorder. Outcome results are summarized for these interventions, as well as some of the major activities and objectives. The role of family, peer, and school contexts in the treatment of conduct problems and depression is highlighted.
World Englishes and Sociolinguistic Theory
Authors: Sharma Devyani
Published: March 2016

This chapter reviews the relationship between sociolinguistic theory and the empirical domain of World Englishes. Despite considerable potential for mutual exchange, sociolinguistic theory has not been the primary analytic model for World Englishes. Using examples from multilingual cultures around the world, the chapter illustrates how postcolonial English contexts can test the validity of classic tenets of sociolinguistic theory. These include principles pertaining to class, gender, style, age, network, peer effects, apparent time, and identity, all of which were initially based on observations in monolingual urban Western contexts. The discussion then turns to the importance of such testable theoretical claims for deeper understandings of the social dynamics of variation and change in World Englishes.
Political Communication
Authors: Kenski Kate , Jamieson Kathleen Hall
Published: March 2016

Two recent changes in the political arena should prompt a rethinking of our theories and definitions of political communication: the emergence of trans-national and non-national actors on the international political stage and the enhanced ability of individuals to convey messages to large scale audiences. For example, the entity called IS, ISIL or ISIS has demonstrated that it can set the agendas of both legacy media and elected leaders with evocative messaging that reaches a mass public while at the same time bypassing traditional media gatekeepers. This chapter argues that our theories about the altered relationships among leaders, media, and publics should forsake key assumptions in the “transmission” model, are amendable to a focus on message, and reconsider concepts such as the two-step flow. This changed environment requires as well that a definition of political communication include a concept of power not predicated on top-down models of understanding.
Improvisation in Freestyle Rap
Authors: Hisama Ellie M.
Published: March 2016

This chapter explores the process of improvisation by emcees in freestyle, or improvised, rap. Drawing on interviews with and writings by freestyle practitioners as well as on recent scholarship in linguistic anthropology, social psychology, and sociology, it argues that freestyle is an everyday activity and a fundamentally social act. The chapter examines a recent study that uses functional magnetic resonance imaging (fMRI) to measure cognitive activity of improvising emcees, and it suggests that the study’s physical constraints on the emcees, its focus on emcees in isolation rather than on those improvising in a cipher (a group of people who take turns improvising rhymes), and its lack of attention to the effects of gender, race, ethnicity, and other identifications on freestyle performance limit the force of its conclusions.
Pacifism
Authors: Ryan Cheyney
Published: March 2016

Pacifism is the alternative to just war theory. In its strongest form, it is fundamentally opposed to war, unconditionally and absolutely. Because the pacifist position is undertheorised, a principal aim of this chapter is to review its main elements with an eye to further discussion. Two types of pacifism, personal and political, are discussed. The first is more religiously based and opposes war because it opposes all individual acts of killing. The second emerges from the Enlightenment, then coalesces in the nineteenth century. It opposes war because it opposes the war system and all acts of war as instances of that system. Some classical objections to pacifism are considered, as well as some new developments, such as ‘contingent pacifism’. Ultimately, the quarrel between just war theory and pacifism can only be resolved by expanding the discussion of war to include historical and institutional considerations.
Sex, Sexual Orientation, and Depression
Authors: McLaughlin Katie , Hatzenbuehler Mark L.
Published: March 2016

Females and lesbian, gay, and bisexual (LGB) populations are twice as likely to develop depression as males and heterosexuals, respectively. This chapter reviews the descriptive epidemiology of sex and sexual orientation differences in depression, and discusses explanations for these group differences, including neurobiological (e.g., differences in limbic system reactivity), individual (e.g., cognitive and affective processes), and interpersonal processes (e.g., victimization experiences), as well as structural influences (e.g., state-level policies that differentially target gays and lesbians for social exclusion). The chapter summarizes common vulnerabilities to depression in females and sexual minorities and offers several directions for future research, including the need for multimethod, multilevel approaches that can increase our understanding of the emergence and persistence of differences in depression based on sex and sexual orientation.
Dying Children and the Kindness of Strangers
Authors: Lantos John
Published: March 2016

This chapter examines kindness to strangers as a modern way of death for terminally ill children, whereby the latter are moved out of their own community and into the strange world of the tertiary-care medical center. Drawing on fiction, poetry, film, and memoir, it discusses the implications of the kindness-to-strangers approach and what the experience is like for the parents and families. It also looks at the tension between despair and hope as a central problem for physicians and parents who care for dying children, as well as the emotions felt by the parents—denial, profound grief, uncertainty, and isolation. In addition, the author considers how medical centers have tried to address the unique challenges that come with caring for dying children. Finally, it reviews some studies of pediatric palliative care offered by children’s hospitals.
Suzaku follow-up of heavily obscured active galactic nuclei detected in Swift/BAT survey: NGC 1106, UGC 03752, and NGC 2788A
Authors: Tanimoto Atsushi , Ueda Yoshihiro , Kawamuro Taiki , Ricci Claudio
Published: March 2016

We present the broad-band (0.5–100 keV) spectra of three heavily obscured active galactic nuclei (AGNs), NGC 1106, UGC 03752, and NGC 2788A, observed with Suzaku and the Swift/Burst Alert Telescope (BAT). The targets are selected from the Swift/BAT 70-month catalog on the basis of their high hardness ratio between above and below 10 keV, and their X-ray spectra are reported here for the first time. We apply three models: a conventional model utilizing an analytic reflection code, and two Monte Carlo based torus models with a doughnut-like geometry (MYTorus: Murphy & Yaqoob, 2009, MNRAS, 397, 1549) and with a nearly spherical geometry (Ikeda torus: Ikeda et al., 2009, ApJ, 692, 608). The three models can successfully reproduce the spectra, and the Ikeda torus model gives a better description than the MYTorus model in all targets. We identify NGC 1106 and NGC 2788A as Compton-thick AGNs. We point out that the common presence of unabsorbed reflection components below 7.1 keV in obscured AGNs, as observed from UGC 03752, is evidence for clumpy tori. This implies that detailed studies utilizing clumpy torus models are required to reach correct interpretation of the X-ray spectra of AGNs.
Measuring the Unequal Gains from Trade
*
Authors: Fajgelbaum Pablo D. , Khandelwal Amit K.
Published: March 2016

Individuals that consume different baskets of goods are differentially affected by relative price changes caused by international trade. We develop a methodology to measure the unequal gains from trade across consumers within countries. The approach requires data on aggregate expenditures and parameters estimated from a nonhomothetic gravity equation. We find that trade typically favors the poor, who concentrate spending in more traded sectors.
Allometric scaling of intraspecific space use
Authors: Rosten Carolyn M. , Gozlan Rodolphe E. , Lucas Martyn C.
Published: March 2016

Allometric scaling relationships enable exploration of animal space-use patterns, yet interspecific studies cannot address many of the underlying mechanisms. We present the first intraspecific study of home range (HR) allometry relative to energetic requirements over several orders of magnitude of body mass, using as a model the predatory fish, pike
Esox lucius
. Analogous with interspecific studies, we show that space use increases more rapidly with mass (exponent = 1.08) than metabolic scaling theories predict. Our results support a theory that suggests increasing HR overlap with body mass explains many of these differences in allometric scaling of HR size. We conclude that, on a population scale, HR size and energetic requirement scale allometrically, but with different exponents.
Debunking the viper's strike: harmless snakes kill a common assumption
Authors: Penning David A. , Sawvel Baxter , Moon Brad R.
Published: March 2016

To survive, organisms must avoid predation and acquire nutrients and energy. Sensory systems must correctly differentiate between potential predators and prey, and elicit behaviours that adjust distances accordingly. For snakes, strikes can serve both purposes. Vipers are thought to have the fastest strikes among snakes. However, strike performance has been measured in very few species, especially non-vipers. We measured defensive strike performance in harmless Texas ratsnakes and two species of vipers, western cottonmouths and western diamond-backed rattlesnakes, using high-speed video recordings. We show that ratsnake strike performance matches or exceeds that of vipers. In contrast with the literature over the past century, vipers do not represent the pinnacle of strike performance in snakes. Both harmless and venomous snakes can strike with very high accelerations that have two key consequences: the accelerations exceed values that can cause loss of consciousness in other animals, such as the accelerations experienced by jet pilots during extreme manoeuvres, and they make the strikes faster than the sensory and motor responses of mammalian prey and predators. Both harmless and venomous snakes can strike faster than the blink of an eye and often reach a target before it can move.
Differential scaling within an insect compound eye
Authors: Perl Craig D. , Niven Jeremy E.
Published: March 2016

Environmental and genetic influences cause individuals of a species to differ in size. As they do so, organ size and shape are scaled to available resources whilst maintaining function. The scaling of entire organs has been investigated extensively but scaling within organs remains poorly understood. By making use of the structure of the insect compound eye, we show that different regions of an organ can respond differentially to changes in body size. Wood ant (Formica rufa) compound eyes contain facets of different diameters in different regions. When the animal body size changes, lens diameters from different regions can increase or decrease in size either at the same rate (a ‘grade’ shift) or at different rates (a ‘slope’ shift). These options are not mutually exclusive, and we demonstrate that both types of scaling apply to different regions of the same eye. This demonstrates that different regions within a single organ can use different rules to govern their scaling, responding differently to their developmental environment. Thus, the control of scaling is more nuanced than previously appreciated, diverse responses occurring even among homologous cells within a single organ. Such fine control provides a rich substrate for the diversification of organ morphology.
The rediscovery of Palmyra and its dissemination in
Philosophical Transactions
Authors: Astengo Gregorio
Published: March 2016

This paper examines the first publicly documented western encounter with the ancient city of Palmyra as an archaeological site. This encounter was achieved in the late seventeenth century by a group of British merchants, who reached Palmyra and made drawings and reports of its ruins. The reports were then published in
Philosophical Transactions
in the mid 1690s. This paper points to the ways in which such accounts came into being, as well as how the city was described and publicly communicated for the first time in
Philosophical Transactions
. These articles had a great impact throughout the following centuries as a reference for the study of Palmyra. This paper therefore also stresses the pivotal role of
Philosophical Transactions
for the production and dissemination of Palmyra's archaeological legacy, as well as for the development of early modern archaeology within the early Royal Society.
Divergent polo box domains underpin the unique kinetoplastid kinetochore
Authors: Nerusheva Olga O. , Akiyoshi Bungo
Published: March 2016

Kinetochores are macromolecular machines that drive eukaryotic chromosome segregation by interacting with centromeric DNA and spindle microtubules. While most eukaryotes possess conventional kinetochore proteins, evolutionarily distant kinetoplastid species have unconventional kinetochore proteins, composed of at least 19 proteins (KKT1–19). Polo-like kinase (PLK) is not a structural kinetochore component in either system. Here, we report the identification of an additional kinetochore protein, KKT20, inTrypanosoma brucei. KKT20 has sequence similarity with KKT2 and KKT3 in the Cys-rich region, and all three proteins have weak but significant similarity to the polo box domain (PBD) of PLK. These divergent PBDs of KKT2 and KKT20 are sufficient for kinetochore localizationin vivo. We propose that the ancestral PLK acquired a Cys-rich region and then underwent gene duplication events to give rise to three structural kinetochore proteins in kinetoplastids.
Cytokine responses in birds challenged with the human food-borne pathogenCampylobacter jejuniimplies a Th17 response
Authors: Reid William D. K. , Close Andrew J. , Humphrey Suzanne , Chaloner Gemma , Lacharme-Lora Lizeth , Rothwell Lisa , Kaiser Pete , Williams Nicola J. , Humphrey Tom J. , Wigley Paul , Rushton Stephen P.
Published: March 2016

Development of process orientated understanding of cytokine interactions within the gastrointestinal tract during an immune response to pathogens requires experimentation and statistical modelling. The immune response against pathogen challenge depends on the specific threat to the host. Here, we show that broiler chickens mount a breed-dependent immune response toCampylobacter jejuniinfection in the caeca by analysing experimental data using frequentist and Bayesian structural equation models (SEM). SEM provides a framework by which cytokine interdependencies, based on prior knowledge, can be tested. In both breeds important cytokines including pro-inflammatory interleukin (IL)-1β, , IL-4, IL-17A, interferon (IFN)-γ and anti-inflammatory IL-10 and transforming growth factor (TGF)-β4 were expressed post-challenge. The SEM revealed a putative regulatory pathway illustrating a T helper (Th)17 response and regulation of IL-10, which is breed-dependent. The prominence of the Th17 pathway indicates the cytokine response aims to limit the invasion or colonization of an extracellular bacterial pathogen but the time-dependent nature of the response differs between breeds.
InGaAs/InAlAs single photon avalanche diode for 1550 nm photons
Authors: Meng Xiao , Xie Shiyu , Zhou Xinxin , Calandri Niccolò , Sanzaro Mirko , Tosi Alberto , Tan Chee Hing , Ng Jo Shien
Published: March 2016

A single photon avalanche diode (SPAD) with an InGaAs absorption region, and an InAlAs avalanche region was designed and demonstrated to detect 1550 nm wavelength photons. The characterization included leakage current, dark count rate and single photon detection efficiency as functions of temperature from 210 to 294 K. The SPAD exhibited good temperature stability, with breakdown voltage dependence of approximately 45 mV K
−1
. Operating at 210 K and in a gated mode, the SPAD achieved a photon detection probability of 26% at 1550 nm with a dark count rate of 1 × 10
8
 Hz. The time response of the SPAD showed decreasing timing jitter (full width at half maximum) with increasing overbias voltage, with 70 ps being the smallest timing jitter measured.
An integrated approach to historical population assessment of the great whales: case of the New Zealand southern right whale
Authors: Jackson Jennifer A. , Carroll Emma L. , Smith Tim D. , Zerbini Alexandre N. , Patenaude Nathalie J. , Baker C. Scott
Published: March 2016

Accurate estimation of historical abundance provides an essential baseline for judging the recovery of the great whales. This is particularly challenging for whales hunted prior to twentieth century modern whaling, as population-level catch records are often incomplete. Assessments of whale recovery using pre-modern exploitation indices are therefore rare, despite the intensive, global nature of nineteenth century whaling. Right whales (Eubalaenaspp.) were particularly exploited: slow swimmers with strong fidelity to sheltered calving bays, the species made predictable and easy targets. Here, we present the first integrated population-level assessment of the whaling impact and pre-exploitation abundance of a right whale, the New Zealand southern right whale (E. australis). In this assessment, we use a Bayesian population dynamics model integrating multiple data sources: nineteenth century catches, genetic constraints on bottleneck size and individual sightings histories informing abundance and trend. Different catch allocation scenarios are explored to account for uncertainty in the population's offshore distribution. From a pre-exploitation abundance of 28 800–47 100 whales, nineteenth century hunting reduced the population to approximately 30–40 mature females between 1914 and 1926. Today, it stands at less than 12% of pre-exploitation abundance. Despite the challenges of reconstructing historical catches and population boundaries, conservation efforts of historically exploited species benefit from targets for ecological restoration.
Histology and affinity of anaspids, and the early evolution of the vertebrate dermal skeleton
Authors: Keating Joseph N. , Donoghue Philip C. J.
Published: March 2016

The assembly of the gnathostome bodyplan constitutes a formative episode in vertebrate evolutionary history, an interval in which the mineralized skeleton and its canonical suite of cell and tissue types originated. Fossil jawless fishes, assigned to the gnathostome stem-lineage, provide an unparalleled insight into the origin and evolution of the skeleton, hindered only by uncertainty over the phylogenetic position and evolutionary significance of key clades. Chief among these are the jawless anaspids, whose skeletal composition, a rich source of phylogenetic information, is poorly characterized. Here we survey the histology of representatives spanning anaspid diversity and infer their generalized skeletal architecture. The anaspid dermal skeleton is composed of odontodes comprising spheritic dentine and enameloid, overlying a basal layer of acellular parallel fibre bone containing an extensive shallow canal network. A recoded and revised phylogenetic analysis using equal and implied weights parsimony resolves anaspids as monophyletic, nested among stem-gnathostomes. Our results suggest the anaspid dermal skeleton is a degenerate derivative of a histologically more complex ancestral vertebrate skeleton, rather than reflecting primitive simplicity. Hypotheses that anaspids are ancestral skeletonizing lampreys, or a derived lineage of jawless vertebrates with paired fins, are rejected.
Perspectives on optimal control of varicella and herpes zoster by mass routine varicella vaccination
Authors: Betta Monica , Laurino Marco , Pugliese Andrea , Guzzetta Giorgio , Landi Alberto , Manfredi Piero
Published: March 2016

Herpes zoster arises from reactivation of the varicella–zoster virus (VZV), causing varicella in children. As reactivation occurs when cell-mediated immunity (CMI) declines, and there is evidence that re-exposure to VZV boosts CMI, mass varicella immunization might increase the zoster burden, at least for some decades. Fear of this natural zoster boom is the main reason for the paralysis of varicella immunization in Europe. We apply optimal control to a realistically parametrized age-structured model for VZV transmission and reactivation to investigate whether feasible varicella immunization paths that are optimal in controlling both varicella and zoster exist. We analyse the optimality system numerically focusing on the role of the cost functional, of the relative zoster–varicella cost and of the planning horizon length. We show that optimal programmes will mostly be unfeasible for public health owing to their complex temporal profiles. This complexity is the consequence of the intrinsically antagonistic nature of varicella immunization programmes when aiming to control both varicella and zoster. However, we show that gradually increasing—hence feasible—vaccination schedules can perform better than routine programmes with constant vaccine uptake. Finally, we show the optimal profiles of feasible programmes targeting mitigation of the post-immunization natural zoster boom with priority.
Royal decree: gene expression in transgenerationally immune primed bumblebee workers mimics a primary immune response
Authors: Barribeau Seth M , Schmid-Hempel Paul , Sadd Ben M
Published: March 2016

Invertebrates lack the cellular and physiological machinery of the adaptive immune system, but show specificity in their immune response [1, 2] and immune priming [3-11]. Functionally, immune priming is comparable to immune memory in vertebrates. Individuals that have survived exposure to a given parasite are better protected against subsequent exposures. Protection may be cross-reactive (e.g. [12]), but demonstrations of persistent and specific protection in invertebrates are increasing [3, 5]. This immune priming can cross generations ("trans-generational" immune priming) [4, 8], preparing offspring for the prevailing parasite environment. While these phenomena gain increasing support, the mechanistic foundations underlying such immune priming, both within and across generations, remain largely unknown. Using a transcriptomic approach, we show a bacterial challenge to bumblebee queens, known to induce trans-generational immune priming, alters daughter (worker) gene expression. Daughters, even when unchallenged themselves, constitutively express a core set of the genes induced upon direct bacterial exposure, including high expression of antimicrobial peptides, a beta-glucan receptor protein implicated in bacterial recognition and the induction of the toll signaling pathway[13], and slit-3 which is important in honeybee immunity[14]. Maternal challenge results in a distinct upregulation of their daughters' immune system, with a signature overlapping with the induced individual response to a direct immune challenge. This will mediate mother-offspring protection, but also associated costs related to reconfiguration of constitutive immune expression. Identification of conserved immune pathways in memory-like responses has important implications for our understanding of the innate immune system, including the innate components in vertebrates, which share many of these pathways[15].
Pathway-Structured Predictive Model for Cancer Survival Prediction: A Two-Stage Approach
Authors: Zhang Xinyan , Li Yan , Akinyemiju Tomi , Ojesina Akinyemi I. , Buckhaults Phillip , Liu Nianjun , Xu Bo , Yi Nengjun
Published: March 2016

Heterogeneity in terms of tumor characteristics, prognosis, and survival among cancer patients has been a persistent problem for many decades. Currently, prognosis and outcome predictions are made based on clinical factors and/or by incorporating molecular profiling data. However, inaccurate prognosis and prediction may result by using only clinical or molecular information directly. One of the main shortcomings of past studies is the failure to incorporate prior biological information into the predictive model, given strong evidence of pathway-based genetic nature of cancer, i.e. the potential for oncogenes to be grouped into pathways based on biological functions such as cell survival, proliferation and metastatic dissemination.

To address this problem, we propose a two-stage procedure to incorporate pathway information into the prognostic modeling using large-scale gene expression data. In the first stage, we fit all predictors within each pathway using penalized Cox model (Lasso, Ridge and Elastic Net) and Bayesian hierarchical Cox model. In the second stage, we combine the cross-validated prognostic scores of all pathways obtained in the first stage as new predictors to build an integrated prognostic model for prediction. We apply the proposed method to analyze breast cancer data from The Cancer Genome Atlas (TCGA), predicting overall survival using clinical data and gene expression profiling. The data includes ~20000 genes mapped into 109 pathways for 505 patients. The results show that the proposed approach not only improves survival prediction compared with the alternative analysis that ignores the pathway information, but also identifies significant biological pathways.
A proposed rule for updating of the head direction cell reference frame following rotations in three dimensions
Authors: Wilson Jonathan , Page Hector , Jeffery Kate J.
Published: March 2016

In the mammalian brain, allocentric (Earth-referenced) heading direction, called azimuth, is encoded by head direction (HD) cells, which fire according to the facing direction of the rat’s head. If the animal is on a horizontal surface then egocentric (self-referenced) rotations of the head around the dorso-ventral axis, called yaw, correspond to changes in azimuth, and elicit appropriate updating of the HD signal. However, if the surface is sloping steeply then yaw rotations no longer map linearly to changes in azimuth. The brain could avoid the complex computations needed to compute global azimuth simply by always firing according to direction on the local surface; however, if the animal moves between surfaces having different compass orientations then errors would accumulate in the subsequent azimuth signal. These errors could be avoided if the HD system instead combines two updating rules: yaw rotations around the D-V axisandrotations of the D-V axis around the gravity-defined vertical axis. We show here that when rats move between vertical walls of different orientations then HD cells indeed rotate their activity by an amount corresponding to the amount of vertical-axis rotation. With modelling, we then show how this reference-frame rotation, which may be driven by inputs from the vestibular nuclei or vestibulocerebellum, allows animals to maintain a simple yaw-based updating rule while on a given plane, but also to avoid accumulation of heading errors when moving between planes, thus facilitating orientation during complex real-world navigation.
Common species link global ecosystems to climate change
Authors: Hannisdal Bjarte , Haaga Kristian Agasøster , Reitan Trond , Diego David , Liow Lee Hsiang
Published: March 2016

Common species shape the world around us, and changes in their commonness signify large-scale shifts in ecosystem structure and function1-4. Dominant taxa drive productivity and biogeochemical cycling, in direct interaction with abiotic components of the Earth system3,4. However, our understanding of the dynamic response of ecosystems to global environmental changes in the past is limited by our ability to robustly estimate fossil taxonomic richness5,6, and by our neglect of the importance of common species. To rectify this, we use observations of the most common and widespread species to track global changes in their distribution in the deep geological past. Our simple approach is robust to factors that bias richness estimators, including widely used sampling-standardization methods5, which we show are highly sensitive to variability in the species-abundance distribution. Causal analyses of common species frequency in the deep-sea sedimentary record detect a lagged response in the ecological prominence of planktonic foraminifera to oceanographic changes captured by deep-ocean temperature records over the last 65 million years, encompassing one of Earth's major climate transitions. Our results demonstrate that common species can act as tracers of a past global ecosystem and its response to physical changes in Earth's dynamic history.
Genetic predictors of gene expression associated with risk of bipolar disorder
Authors: Shah Kaanan P. , Wheeler Heather E. , Gamazon Eric R. , Nicolae Dan L. , Cox Nancy J. , Im Hae Kyung
Published: March 2016

Bipolar disorder (BD) affects the quality of life of approximately 1% of the population and represents a major public health concern. It is known to be highly heritable but large-scale genome-wide association studies (GWAS) have discovered only a handful of markers associated with the disease. Furthermore, the biological mechanisms underlying these markers need to be elucidated. We recently published a gene-level association test, PrediXcan that integrates transcriptome regulation data to characterize the function of these markers in a tissue specific manner. In this study, we developed prediction models for mRNA levels in 10 brain regions using data from the GTEx project and performed PrediXcan analysis in WTCCC as well as in an independent cohort, GAIN. We replicate the association between predicted expression ofPTPREand BD risk in whole blood and recapitulate the association in brain tissues.PTPREencodes the protein tyrosine phosphatase, receptor type E, that is known to be involved in RAS signaling and activation of voltage-gated K+ channels. We also found a new genome-wide significant association between lower predicted expression ofBBX(bobby sox homolog) in the anterior cingulate cortex region of the brain and increased risk of BD (pWTCCC= 7.02 x 10−6, pGAIN= 4.68 x 10−3,pmeta= 1.11 x 10−7). In sum, we used our mechanistically informed approach, PrediXcan, to identify and replicate two novel genome-wide significant genes using existing GWAS studies.
Local RhoA Activation Induces Cytokinetic Furrows Independent of Spindle Position and Cell Cycle Stage
Authors: Wagner Elizabeth , Glotzer Michael
Published: March 2016

Cytokinetic cleavage furrows assemble during anaphase at a site that is dictated by the position of the spindle. The GTPase RhoA promotes contractile ring assembly and furrow ingression during cytokinesis. While many factors that regulate RhoA during cytokinesis have been characterized, the spatiotemporal regulatory logic remains undefined. It is not known whether a local zone of RhoA activity is sufficient to induce furrow formation or whether the spindle modulates furrow assembly through other pathways. Similarly, it is not known whether the entire cortex is responsive to RhoA, nor whether contractile ring assembly is cell cycle regulated. Here, we have developed an optogenetic probe to gain tight spatial and temporal control of RhoA activity in mammalian cells and demonstrate that cytokinetic furrowing is primarily regulated at the level of RhoA activation. Light-mediated recruitment of a RhoGEF domain to the plasma membrane leads to rapid activation of RhoA, leading to assembly of cytokinetic furrows that partially ingress. Furthermore, furrow formation in response to RhoA activation is not spatially or temporally restricted. RhoA activation is sufficient to generate furrows at both the cell equator and at cell poles, in both metaphase and anaphase. Remarkably, furrow formation can be initiated in rounded interphase cells, but not adherent cells. These results indicate RhoA activation is sufficient to induce assembly of functional contractile rings and that cell rounding facilitates furrow formation.
Trophoblast survival signaling during human placentation requires HIF-induced transcription of HSP70
Authors: Jain Chandni V. , Jessmon Philip , Barrak Charbel T. , Bolnik Alan D. , Kilburn Brian A. , Hertz Michael , Randall Armant D.
Published: March 2016

Survival of trophoblast cells in the low oxygen environment of human placentation requires metalloproteinase-mediated shedding of HBEGF and downstream signaling. A matrix metalloproteinase (MMP) antibody array and quantitative RT-PCR revealed upregulation of MMP2 post-transcriptionally in human first trimester HTR-8/SVneo trophoblast cells and placental explants exposed to 2% O2. Specific MMP inhibitors established the requirement for MMP2 in HBEGF shedding and upregulation. Hypoxia inducible factors, HIF1A and EPAS1 (HIF2A), accumulated at 2% O2, and HIF target genes were identified by next-generation sequencing of RNA from trophoblast cells cultured at 2% O2for 0, 1, 2 and 4 hrs. Of nine genes containing HIF-response elements upregulated at 1 hour, only HSPA6 (HSP70B’) remained elevated after 4 hours. The HSP70 chaperone inhibitor VER155008 blocked upregulation of both MMP2 and HBEGF at 2% O2, and increased apoptosis. However, both HBEGF upregulation and apoptosis were rescued by exogenous MMP2. We propose that MMP2-mediated shedding of HBEGF, initiated by HSP70, contributes to trophoblast survival at the low O2levels encountered during the first trimester, and is essential for successful pregnancy outcomes.

Summary Statement

Trophoblast survival during human placentation, when oxygenation is minimal, required HIF-induced transcription of HSP70, which mediated MMP2 accumulation and the transactivation of anti-apoptotic ERBB signaling by HBEGF shedding.
Left-right leaf asymmetry in decussate and distichous phyllotactic systems
Authors: Martinez Ciera C. , Chitwood Daniel H. , Smith Richard S. , Sinha Neelima R.
Published: March 2016

Leaves in plants with spiral phyllotaxy exhibit directional asymmetries, such that all the leaves originating from a meristem of a particular chirality are similarly asymmetric relative to each other. Models of auxin flux capable of recapitulating spiral phyllotaxis predict handed auxin asymmetries in initiating leaf primordia with empirically verifiable effects on superficially bilaterally symmetric leaves. Here, we extend a similar analysis of leaf asymmetry to decussate and distichous phyllotaxy. We found that our simulation models of these two patterns predicted mirrored asymmetries in auxin distribution in leaf primordia pairs. To empirically verify the morphological consequences of asymmetric auxin distribution, we analyzed the morphology of a tomatosister-of-pinformed1a(sopin1a) mutant,entire-2, in which spiral phyllotaxy consistently transitions to a decussate state. Shifts in the displacement of leaflets on the left and right sides ofentire-2leaf pairs mirror each other, corroborating predicted model results. We then analyze the shape of >800 commonivy (Hedera helix) and >3,000 grapevine (VitisandAmpelopsisspp.) leaf pairs and find statistical enrichment of predicted mirrored asymmetries. Our results demonstrate that left-right auxin asymmetries in models of decussate and distichous phyllotaxy successfully predict mirrored asymmetric leaf morphologies in superficially symmetric leaves.
Transdermal electrical neuromodulation of the trigeminal sensory nuclear complex improves sleep quality and mood
Authors: Boasso Alyssa M. , Mortimore Hailey , Silva Rhonda , Aven Linh , Tyler William J.
Published: March 2016

Achieving optimal human performance that involves cognitive or physical work requires quality sleep and a positive mental attitude. The ascending reticular activating system (RAS) represents a powerful set of endogenous neuromodulatory circuits that gate and tune global brain responses to internal and external cues, thereby regulating consciousness, alertness, and attention. The activity of two major RAS nuclei, the locus coeruleus (LC) and pedunculopontine nucleus (PPN), can be altered by trigeminal nerve modulation. Monosynaptic afferent inputs from the sensory components of trigeminal nerve branches project to the trigeminal sensory nuclear complex (TSNC), which has direct and polysynaptic connections to the LC and PPN. We previously found high-frequency (7 – 11 kHz) transdermal electrical neuromodulation (TEN) of the trigeminal nerve rapidly induces physiological relaxation, dampens sympathetic nervous system responses to acute stress, and suppresses levels of noradrenergic biomarkers. Given the established roles of LC and PPN neuronal activity in sleep regulation, psychophysiological arousal, and stress, we conducted three studies designed to test hypotheses that modulation of the TSNC can improve sleep quality and mood in healthy individuals (n = 99). Across a total of 1,386 days monitored, we observed TEN modulation of trigeminal and cervical nerves prior to sleep onset produced significant improvements in sleep quality and affective states, quantified using clinically validated surveys, overnight actigraph and heart rate recordings, and biochemical analyses compared to baseline or sham controls. Moreover, we observed some frequency dependence in that TEN delivered at lower frequencies (TENLF; 0.50 – 0.75 kHz) was significantly more effective at improving sleep quality and reducing anxiety than higher frequency TEN waveforms. Collectively our results indicate that transdermal electrical neuromodulation of trigeminal and cervical nerve branches can influence TSNC activity in a manner that significantly improves sleep quality and significantly reduces stress. We conclude that biasing RAS network activity to optimize sleep efficiency and enhance mood by electrically modulating TSNC activity through its afferent inputs holds tremendous potential for optimizing mental health and human performance.
Crystal structure of histone-like protein fromStreptococcus mutansrefined to 1.9 Å resolution
Authors: O'Neil Pierce , Lovell Scott , Mehzabeen Nurjahan , Battaile Kevin , Biswas Indranil
Published: March 2016

Nucleoid-associated proteins (NAPs) in prokaryotes play an important architectural role in DNA bending, supercoiling and DNA compaction. In addition to architectural roles, some NAPs also play regulatory roles in DNA replication and repair, and act as global transcriptional regulators in many bacteria. Bacteria encode multiple NAPs and some of them are even essential for survival.Streptococcus mutans, a dental pathogen, encodes one such essential NAP called histone-like protein (HLP). Here, the three-dimensional structure ofS. mutansHLP has been determined to 1.9 Å resolution. The HLP structure is a dimer and shares a high degree of similarity with other bacterial NAPs, including HU. Since HLPs are essential for the survival of pathogenic streptococci, this structure determination is potentially beneficial for future drug development against these pathogens.