bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Generalized Exanthematous Pustulosis Due to Labetalol Drug Fever and Leukocytosis Caused by Tigecycline Toxic Hepatitis Induced by Methylprednisolone Intravenous Pulse Dosing Mitoxantrone-Related Osteonecrosis of the Jaw Medications with Anticholinergic Effects and Their Implications in the Elderly
Authors: Mancano Michael A.
Published: June 2016

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MEDWATCH program (800-FDA-1088). If you have reported an interesting, preventable ADR to MEDWATCH, please consider sharing the account with our readers.
Carboplatin and Liposomal Doxorubicin for Ovarian Cancer
Authors: Nguyen Jamie , Solimando Dominic A. , Waddell J. Aubrey
Published: June 2016

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
Reducing Readmission at an Academic Medical Center: Results of a Pharmacy-Facilitated Discharge Counseling and Medication Reconciliation Program
Authors: Zemaitis Christopher T. , Morris Ginger , Cabie Maribeth , Abdelghany Osama , Lee Lorraine
Published: June 2016

Background

Hospital readmission has been identified as a key quality indicator and a target for reducing health care spending.

Objective

To evaluate the impact of a pharmacy-facilitated medication reconciliation and patient education model with post discharge follow-up on 30-day readmissions.

Methods

This prospective, historical control study included all patients admitted during a 6-month period to a general medicine unit with the highest 30-day readmission rate at Yale-New Haven Hospital. Patients were excluded if they expired prior to discharge, transferred, left against medical advice, were discharged to hospice, or were previously enrolled in the study. Upon admission, pharmacy technicians compiled the medication reconciliation information. Interventions were made by the pharmacist communicating with the patient's primary team. Medication and disease state counseling and final medication reconciliation were performed by the pharmacist before discharge. The primary outcome measure was 30-day readmission rates during the intervention period compared to the preceding 6 months and the same time period the previous year. Secondary outcomes included the total number of pharmacist-identified medication reconciliation interventions, total pharmacy resource utilization, and identification of patients at high risk for readmission.

Results

Study outcomes showed a 27% reduction in readmission during the intervention period. The pharmacist made a total of 546 medication interventions. The average pharmacist and pharmacy technician time per patient were 28.9 and 23.7 minutes, respectively.

Conclusions

Pharmacy-facilitated medication reconciliation and patient education of medicine patients decreased 30-day readmission rates.
Uridine Triacetate
Authors: Cada Dennis J. , Mbogu Uzoma , Bindler Ross J. , Baker Danial E.
Published: June 2016

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. The June 2016 monograph topics are elbasvir/grazoprevir, ixekizumab, brivaracetam, reslizumab, and sofosbuvir/velpatasvir. The Safety MUE is on reslizumab.
Review of the 2015 Drug Supply Chain Security Act
Authors: Brechtelsbauer Erich D. , Pennell Benjamin , Durham Mary , Hertig John B. , Weber Robert J.
Published: June 2016

The integrity of the pharmaceutical supply chain is threatened by medication counterfeiting, importation of unapproved and substandard drugs, and grey markets – all of which have the potential to distribute drug products with the potential for serious harm. On November 27, 2013, President Obama signed into law Title II of the Drug Quality and Security Act, now known as the Drug Supply Chain Security Act (DSCSA). Over the next 10 years, the DSCSA will require the pharmaceutical supply chain to implement medication tracking and tracing; serialization, verification, and detection of suspicious products; and strict guidelines for wholesaler licensing and reporting. This article reviews the important aspects of the DSCSA and outlines the role of health-system pharmacy leaders in ensuring compliance to the DSCSA. By verifying that medication supplies are free from adulteration and tampering, the DSCSA serves as a foundational law to ensure quality in providing patient-centered pharmacy services.
Digital Health Solutions: An Important Tool in Patient Engagement
Authors: Fox Brent I. , Pinto Brian
Published: June 2016

Hospitals and health systems are facing increased pressure to improve quality and outcomes while reducing expense. Quality-based reimbursement models are providing the necessary incentives for health care institutions to focus on issues such as avoidable hospital-acquired conditions and 30-day readmission rates. While our health care facilities certainly play a vital role in achieving optimal outcomes, patient engagement remains at the center of these efforts.
La responsabilidad pedagógica de los profesores de educación especial: una investigación desde el método «FH» de Max van Manen
Authors: Jordán Sierra José Antonio , Arriagada Vidal Jessica Jeannette
Published: June 2016

Este articulo muestra, de forma sintética, una investigación realizada por los autores sobre lo más esencial de la responsabilidad pedagógica de los profesores de educación especial implicados en su relación educativa con sus alumnos con discapacidad intelectual. Los 30 profesores elegidos para participar en tal investigación fueron tanto de Cataluña como de Chile. La metodología investigadora utilizada ha sido poco aplicada –hasta el presente– en España y en Latinoamérica: se trata del «método fenomenológico-hermenéutico», según lo concibe y lo aplica el pedagogo Max van Manen. Tras el breve marco teórico y la descripción de la metodología aplicada, se aporta –en vez de los «análisis de resultados y las conclusiones» de una investigación más convencional– una «muestra selectiva y significativa» del «texto fenomenológico», que tiene como misión sacar a la luz de manera evocadora y formativa los hallazgos esenciales del fenómeno en este caso estudiado.
Dimensiones de la inclusión de las TIC en el currículo educativo: una aproximación teórica
Authors: Urueña López Sergio
Published: June 2016

El presente artículo tiene como principal objetivo analizar desde un punto de vista teórico la triple dimensión que supone la inclusión completa de las Tecnologías de la Información y la Comunicación (TIC) en el currículo educativo. La primera de las dimensiones hace referencia a la inclusión de las tic como herramientas didácticas para el apoyo del ejercicio docente. La segunda alude a su integración como medida de fomento de un uso eficiente de las mismas. Desde la tercera, se sugiere la inclusión de las TIC como objetos de análisis crítico y de conocimiento. Las dos últimas dimensiones señaladas, las más olvidadas aunque no por ello las menos importantes, resultan fundamentales de cara a la promoción de ciudadanos críticos capaces de tomar decisiones razonables e informadas en lo que respecta a la evaluación, diseño, control e implementación de las nuevas tecnologías.
Sobre el potencial crítico de los enfoques sociomateriales en educación
Authors: Decuypere Mathias , Simons Maarten
Published: June 2016

Este artículo tiene como argumento central que el recientemente emergente enfoque sociomaterial tiene un inherente potencial crítico para la educación, pero esta capacidad no ha sido completamente puesta en práctica o explorada en estudios educativos. Para argumentar estas ideas, este artículo empieza, en primer lugar, con una concisa descripción de representacionalismo en contraposición al pensamiento relacional, y propone que los estudios sociomateriales deben situarse en esta última corriente. En consecuencia, la función crítica que es ampliamente apoyada en el pensamiento representacional –que es una función principalmente dirigida a desacreditar y develar– requiere ser repensada. Para concebir nuevamente esta función, el artículo en segundo lugar profundiza sobre las principales características de los estudios sociomateriales en educación para demostrar que tal pensamiento relacional toma forma dentro y durante la realización de la investigación sociomaterial. Estas características son decisivas para aprehender completamente la perspectiva crítica de los enfoques sociomateriales en educación. La función de la crítica, entonces, equivale a una actitud comprometida con las prácticas objeto de investigación y dirige la atención hacia la creatividad crítica que ofrece algunos horizontes de cambio.
Reliability of the predicted stand structure for clear-cut stands using optional methods: airborne laser scanning-based methods, smartphone-based forest inventory application Trestima and pre-harvest measurement tool EMO
Authors: Siipilehto Jouni , Lindeman Harri , Vastaranta Mikko , Yu Xiaowei , Uusitalo Jori
Published: June 2016

Accurate timber assortment information is required before cuttings to optimize wood allocation and logging activities. Timber assortments can be derived from diameter-height distribution that is most often predicted from the stand characteristics provided by forest inventory. The aim of this study was to assess and compare the accuracy of three different pre-harvest inventory methods in predicting the structure of mainly Scots pine-dominated, clear-cut stands. The investigated methods were an area-based approach (ABA) based on airborne laser scanning data, the smartphone-based forest inventory Trestima app and the more conventional pre-harvest inventory method called EMO. The estimates of diameter-height distributions based on each method were compared to accurate tree taper data measured and registered by the harvesterâs measurement systems during the final cut. According to our results, grid-level ABA and Trestima were generally the most accurate methods for predicting diameter-height distribution. ABA provides predictions for systematic 16 m Ã 16 m grids from which stand-wise characteristics are aggregated. In order to enable multimodal stand-wise distributions, distributions must be predicted for each grid cell and then aggregated for the stand level, instead of predicting a distribution from the aggregated stand-level characteristics. Trestima required a sufficient sample for reliable results. EMO provided accurate results for the dominating Scots pine but, it could not capture minor admixtures. ABA seemed rather trustworthy in predicting stand characteristics and diameter distribution of standing trees prior to harvesting. Therefore, if up-to-date ABA information is available, only limited benefits can be obtained from stand-specific inventory using Trestima or EMO in mature pine or spruce-dominated forests.
Entre os sentidos atribuídos à colaboração e a possibilidade de mudança
Authors: Macário Maria João Bártolo , Sá Cristina Manuela
Published: June 2016

Dada a importância fundamental das representações na vida dos indivíduos e, particularmente, na profissão docente, enquanto influenciadoras da sua ação didática, desenvolveu-se um estudo no âmbito da formação inicial deste grupo profissional. A finalidade era a de compreender as dinâmicas de influência entre as representações, a possibilidade de mudança e a adoção de trabalho colaborativo. Participaram dois grupos de estudantes de uma unidade curricular de um mestrado profissionalizante em Educação Pré-escolar e Ensino no 1º Ciclo do Ensino Básico de uma universidade portuguesa, no ano letivo de 2010/2011. Disponibilizou-se um questionário online no início do estudo e, no fim, deste os estudantes conceberam uma reflexão escrita individual sobre a vivência numa unidade curricular em que se promovia a colaboração. Neste artigo pretendemos apresentar e discutir as representações destas duas fases do estudo. Os resultados apontam para a influência das representações sobre colaboração na adoção dessa modalidade de trabalho e a dificuldade de mudança, ainda que essa possibilidade fique em aberto, como veremos. Daqui emergiram algumas sugestões pedagógico-didáticas com vista à promoção de práticas inovadoras no Ensino Superior, centradas na aprendizagem dos estudantes e no desenvolvimento da colaboração, particularmente na formação inicial de professores.
Estudo de adaptação e validação de uma escala de perceção de liderança ética para líderes portugueses
Authors: Neves Maria de Lurdes Gomes , Jordão Filomena , Pina e Cunha Miguel , Vieira Diana Aguiar , Coimbra Joaquim Luís
Published: June 2016

Os líderes influenciam o comportamento individual e organizacional, incluindo a dimensão ética, sendo igualmente influenciados pela suas expetativas, interpretações e interações com os outros (Glynn & Jamerson, 2006; Kellerman, 2004).Frequentemente intervêm em diferentes contextos éticos, o que torna difícil para as pessoas "boas" tomarem boas decisões em situações más" (Glynn & Jamerson, 2006, p. 154).A liderança ética pode ser considerada como a "demonstração de conduta normativamente adequada através de ações pessoais e das relações interpessoais, assim como a promoção de tal conduta para os liderados através de uma comunicação bidireccional, reforço e tomada de decisão" (Brown, Trevino & Harrison, 2005, 9.120).O estudo aqui apresentado teve como objetivo desenvolver uma escala de liderança ética (Hanges & Dickson, 2004) para líderes portugueses com base na adaptação e validação da escala realizada por De Hoog e Den Hartog (2008).Os resultados obtidos evidenciam qualidades psicométicas adequadas, com um valor elevado de consistência interna. As análises fatoriais exploratórias revelam uma estrutura que aponta para a existência de dois fatores para a escala definidos como Liderança Ètica e Liderança Despótica que integram as respetivas dimensões.Importa, futuramente realizar uma análise da estabilidade das escalas com outra amostra por forma a verificar-se a consistência do s valores obtidos.
Escala do Controlo Sociopolítico para Adolescentes: SPCS-Y
Authors: Rodrigues Sofia Dos Santos , Coimbra Joaquim Luís , Correia Alice Natália , Sousa Vânia Ernestina
Published: June 2016

Este estudo tem como intuito a adaptação e validação da Escala de Controlo Sociopolítico (SPCS-Y) a uma amostra de adolescentes. Participaram 393 estudantes de 8º e 9º ano de quatro escolas públicas da Região Norte de Portugal, distrito do Porto, com idades entre 13 e 14 anos. Realizou-se a Análise Fatorial Confirmatória para a validação dos dados. Num total de 17 itens, mantiveram-se 12 itens, distribuídos na mesma estrutura fatorial de dois fatores. As qualidades psicométricas do instrumento permitem-nos afirmar que a SPCS-Y é uma escala que evidencia validade e fiabilidade para avaliar as dimensões da liderança e controlo sociopolítico em adolescentes.
Adaptação da Escala de Empatia com Animais (EEA) para a população portuguesa
Authors: Emauz Ana , Gaspar Augusta , Esteves Francisco , Carvalhosa Susana Fonseca
Published: June 2016

O interesse pelo estudo das relações entre humanos e animais tem vindo a crescer nos últimos anos, mas a empatia para com animais é um tema ainda recente na literatura, levando a uma maior necessidade de desenvolver instrumentos adequados para a medir. A Escala de Empatia para com Animais (EEA, Paul, 2000) é o instrumento mais utilizado, tendo por isso sido escolhido para o presente estudo. Através de uma análise exploratória e confirmatória obteve-se um modelo estrutural com dois componentes, denominados de Desvinculação Emocional (DE) e Preocupação Empática com os Animais (PEA). A estrutura final reporta um modelo bem ajustado, com um bom nível de consistência interna, tanto da escala global, como das suas subescalas. Foi encontrada uma correlação positiva entre a EEA e outra escala de empatia traço dirigida a humanos (IRI), o que  veio reforçar a validade de construto deste instrumento para a sua utilização no panorama nacional.
O estilo de reminiscência nas interações mãe-criança e pai-criança
Authors: Rebelo Ana , Maia Joana , Gatinho Ana , Coelho Leandra , Torres Nuno , Veríssimo Manuela
Published: June 2016

Nas últimas décadas, a investigação na área da reminiscência adulto-criança tem-se debruçado, essencialmente, sobre a forma como as mães conversam sobre eventos passados com os seus filhos. Contudo,mais recentemente, os investigadores têm procurado compreender a importância do pai no desenvolvimento da comunicação infantil. O presente estudo explora as diferenças do estilo de reminiscência nas díades mãe-criança e pai-criança, em função do sexo desta. Participaram 79 crianças portuguesas (40raparigas e 39 rapazes), com uma média de 56.93 meses de idade, e respectivas figuras parentais (mãe, n=75 e pai, n=57), 53 destas tinham dados com as díades mãe e pai. As díades participaram separadamente, numa tarefa de reminiscência sobre três eventos passados partilhados. Investigadores independentes transcreveram as conversas e cotaram o estilo de reminiscência dos pais, das mães e dacriança. Os resultados evidenciam que tanto os pais, como as mães não diferem grandemente na forma como falam do passado com as crianças, no entanto as mães utilizam um discurso mais repetitivo do que os pais. As crianças apresentam uma tendência para falar mais com os pais, do que com as mães, independentemente do sexo. Estes dados reforçam a importância do papel do pai como agente de socialização, desde os primeiros anos, promotor da comunicação da criança com o mundo exterior.
The Number of Pain Sites and Other Non‐pain Symptoms are Important Clues for Diagnosis: A Cross‐sectional Study of Outpatients with Multiple Somatic Complaints
Authors: Kita Keiichiro , Nagatsuma Masahiro , Wakaguri Akira , Sekijima Azusa , Watanabe Fumiko , Kuroiwa Maiko , Miura Taro , Koura Tomoyuki , Yoshida Kiichiro , Kuroiwa Shota , Yamashiro Seiji
Published: June 2016

Background: In general practice, a wide variety of patients often present with various complaints. Some of them have multiple somatic symptoms, and it is possible for a general practitioner to miss an organic disease. In this cross‐sectional study, we retrospectively examined the correlation between the number of complaints and the prevalence of diseases in order to elucidate clues to help detect organic diseases in patients with multiple somatic complaints.

Method: We evaluated 386 new walk‐in outpatients who presented to the department of general medicine at the Toyama University Hospital between January 2014 and December 2014 with pain symptoms. Symptoms were classified by the number of pain sites (NPS) and the number of other non‐pain complaints (NOC). Then we examined the association between these two variables and the final diagnosis.

Results: The prevalence of organic diseases in the four and more NPS group was significantly higher than that of the three or less NPS group (66.7% and 27.5%, respectively). Psychiatric diseases were more prevalent in the group who had three and more NOC than in the patient population with two or less NOC (36.4% and 4.4%, respectively).

Conclusion: Counting NPS and NOC could contribute to proper management of patients with multiple somatic complaints.
Los recursos didácticos de matemáticas en las aulas de educación primaria en América Latina: Disponibilidad e incidencia en el aprendizaje de los estudiantes
Authors: Murillo Torrecilla Francisco Javier , Román Carrasco Marcela , Atrio Cerezo Santiago
Published: June 2016

En este artículo se busca describir la disponibilidad de diferentes recursos didácticos de Matemáticas en las aulas de primaria de América Latina, y determinar si la misma incide en el desempeño de los estudiantes en matemáticas. Para ello se usan los datos del SERCE, desarrollado por la UNESCO, utilizando modelos multinivel de 4 niveles. La muestra está conformada por más de 8.000 aulas de 3º y 6º de primaria de unas 3.000 escuelas de 16 países de América Latina y los 180.000 estudiantes que allí estudian. Los resultados evidencian, por una parte, las importantes carencias y diferencias en el acceso a recursos didácticos específicos con que cuentan los estudiantes latinoamericanos en las aulas de primaria. Por otra, se demuestra que en las aulas donde se dispone de diferentes recursos los estudiantes de primaria obtienen mejores resultados.
Economising, Strategising and the Vertical Boundaries of the firm
Authors: Leahy Dermot , Montagna Catia
Published: June 2016

We bridge the organisational economics and industrial economics literatures on the vertical boundaries of the firm by contextualising the transaction cost approach to the make-or-buy decision within an oligopolistic market structure. Firms invest in the quality of the intermediate resulting in the endogenous determination of the price of the intermediate and marginal production cost of the final good. We highlight new strategic incentives to outsource and/or vertically integrate and show how these incentives can result in asymmetric-mode-of-operations, investment and costs. We apply our model to a number of different international trading setups.
A Marxist Argumentative Scheme on Basic Income and Wage Share in an Anti-capitalist Agenda
Authors: Manjarin Edgar , Szlinder Maciej
Published: June 2016

In this article, we present an anti-capitalist argument for basic income based on its predicted effects on the wage share dynamics and its relation with the working class’ bargaining power. Our considerations are located in the Marxist tradition and based mainly on contributions to the Marxist analytical framework made by Rosa Luxemburg and Michał Kalecki. We argue that basic income should lead to a rise of the share of wages in the GDP, by significantly improving workers’ bargaining position in various ways: through increasing the effective demand and investments by redistributing income to the advantage of the poorer groups of the society; through guaranteeing the realisation of basic needs outside the labour market; through positive influence on the collective bargaining power, especially during a strike; and through enhancing engagement in alternative relations of production as well as in political struggle for a better situation of working people. We also distinguish some necessary conditions in a realistic historical scenario where the positive, anti-capitalist dynamic launched by basic income could be set into motion.
Subsequent and Subsidiary? Rethinking the Role of Applications in Establishing Quantum Mechanics
Authors: James Jeremiah , Joas Christian
Published: June 2016

As part of an attempt to establish a new understanding of the earliest applications of quantum mechanics and their importance to the overall development of quantum theory, this paper reexamines the role of research on molecular structure in the transition from the so-called old quantum theory to quantum mechanics and in the two years immediately following this shift (1926–1928). We argue on two bases against the common tendency to marginalize the contribution of these researches. First, because these applications addressed issues of longstanding interest to physicists, which they hoped, if not expected, a complete quantum theory to address, and for which they had already developed methods under the old quantum theory that would remain valid under the new mechanics. Second, because generating these applications was one of, if not the, principal means by which physicists clarified the unity, generality, and physical meaning of quantum mechanics, thereby reworking the theory into its now commonly recognized form, as well as developing an understanding of the kinds of predictions it generated and the ways in which these differed from those of the earlier classical mechanics. More broadly, we hope with this article to provide a new viewpoint on the importance of problem solving to scientific research and theory construction, one that might complement recent work on its role in science pedagogy.
Fundamental Disputations
Authors: Martin Joseph D.
Published: June 2016

A philosophical debate between particle physicists and solid state physicists roiled as these subdisciplines competed for financial support, social approbation, and intellectual prestige through the second half of the twentieth century. Their disagreement hinged on the nature of fundamental research. The particle physics community adopted a reductionist approach, arguing that the fundamental physical laws were those governing the smallest constituents of matter and energy. Partly in response to this position, solid state physicists developed a range of more permissive perspectives on what type of physics could be fundamental, all of which stressed the importance of higher-level characteristics, maintaining that investigations at many levels of complexity might yield fundamental insight. This paper traces the dispute over fundamentality, which grew both from the specific problems physicists encountered while building their professional infrastructure, and from the demands of funding their research in Cold War America. Through an exploration of how physicists developed philosophical positions within institutional contexts and deployed those positions in their rhetoric, I argue first that professional pressures both motivated and exerted influence over the construction of such views, second that philosophical views had a reciprocal guiding effect on the institutional and professional development of Cold War physics, and third that these views were further bent, blunted, and reshaped when deployed in high-stakes rhetorical discourse. The case studies through which this story unfolds indicate that further attention to such philosophical commitments is warranted when examining the historical development of scientific institutions, communities, and hierarchies.
The Consultants
Authors: Wilson Benjamin
Published: June 2016

After the laser was first demonstrated in 1960, many American defense officials hoped it would become a revolutionary new weapon. At the Institute for Defense Analyses (IDA), a nonprofit advisory corporation contracted to the Defense Department, experts studied the possibility of using lasers to defend against nuclear-tipped ballistic missiles. A few academic consultants for IDA (among them physicists Nicolaas Bloembergen, Charles Townes, Keith Brueckner, and Norman Kroll) began to think about how to generate laser pulses of enormous power and propagate them through the atmosphere. Along the way, in a mix of classified discussions and reports, and through a series of important publications in the open literature, the consultants laid the foundations of a new field: nonlinear optics. Nonlinear optics is the science of the interaction between matter and intense light, and it became a major branch of physics in the 1960s. The field’s history calls for deeper consideration of the ways in which powerful institutions and the production of knowledge were joined in the Cold War era. Though nonlinear optics was every bit “Cold War science,” the conventional and widely used concept of “patronage” seems inadequate for understanding the origins and development of the field. A product of neither government contracts nor innovations in technology alone, nonlinear optics was fashioned by a close-knit and elite community of experts straddling the classified and unclassified domains. The field took its peculiar shape and content within this unique social space—the social world of the Cold War defense consultant.
Associating Physics and Chemistry to Dissociate Molecules
Authors: Petit Axel
Published: June 2016

A case study of the Clausius-Williamson hypothesis sheds light on the development of the physical sciences during the nineteenth century. In the 1850s, Rudolf Clausius and Alexander William Williamson independently developed similar hypotheses at a time when physics and chemistry were beginning to be considered independent endeavors. Some thirty years later, after specialization took root, their names were associated; the two hypotheses became the hypothesis of Clausius-Williamson. How and why were these distinct investigations conducted in the 1850s unified in the 1880s? The current historiography addresses the Clausius-Williamson hypothesis as it is featured in subsequent interpretations by Svante Arrhenius, but does not thoroughly analyze the published writings of Clausius and Williamson themselves. This paper reappraises Clausius’s and Williamson’s works in their original context and analyzes how their hypotheses came to be associated. This case study emphasizes how the relationship between physics and chemistry evolved in the nineteenth century. More specifically, it underscores the limited communication between these disciplines in the 1850s and the rise of interdisciplinarity in the 1880s, which led to the creation of a new field: physical chemistry. From the study of the emergence and success of the theory of ionic dissociation and physical chemistry, I show that referring to the authoritative figures of Clausius and Williamson legitimized and valorized investigations at the borderlands of physics and chemistry in a context of increased specialization.
RNF123 has an E3 ligase‐independent function in RIG‐I‐like receptor‐mediated antiviral signaling
Authors: Wang Shuai , Yang Yong‐Kang , Chen Tao , Zhang Heng , Yang Wei‐Wei , Song Sheng‐Sheng , Zhai Zhong‐He , Chen Dan‐Ying
Published: June 2016

Retinoic acid‐inducible gene I (RIG‐I) and melanoma differentiation‐associated gene 5 (MDA5) are cytoplasmic sensors crucial for recognizing different species of viral RNAs, which triggers the production of type I interferons (IFNs) and inflammatory cytokines. Here, we identify RING finger protein 123 (RNF123) as a negative regulator of RIG‐I and MDA5. Overexpression of RNF123 inhibits IFN‐β production triggered by Sendai virus (SeV) and encephalomyocarditis picornavirus (EMCV). Knockdown or knockout of endogenous RNF123 potentiates IFN‐β production triggered by SeV and EMCV, but not by the sensor of DNA viruses cGAS. RNF123 associates with RIG‐I and MDA5 in both endogenous and exogenous cases in a viral infection‐inducible manner. The SPRY and coiled‐coil, but not the RING, domains of RNF123 are required for the inhibitory function. RNF123 interacts with the N‐terminal CARD domains of RIG‐I/MDA5 and competes with the downstream adaptor VISA/MAVS/IPS‐1/Cardif for RIG‐I/MDA5 CARD binding. These findings suggest that RNF123 functions as a novel inhibitor of innate antiviral signaling mediated by RIG‐I and MDA5, a function that does not depend on its E3 ligase activity.
Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms
Authors: Dove Katja K , Stieglitz Benjamin , Duncan Emily D , Rittinger Katrin , Klevit Rachel E
Published: June 2016

RING‐in‐between‐RING (RBR) ubiquitin (Ub) ligases are a distinct class of E3s, defined by a RING1 domain that binds E2 Ub‐conjugating enzyme and a RING2 domain that contains an active site cysteine similar to HECT‐type E3s. Proposed to function as RING/HECT hybrids, details regarding the Ub transfer mechanism used by RBRs have yet to be defined. When paired with RING‐type E3s, E2s perform the final step of Ub ligation to a substrate. In contrast, when paired with RBR E3s, E2s must transfer Ub onto the E3 to generate a E3~Ub intermediate. We show that RBRs utilize two strategies to ensure transfer of Ub from the E2 onto the E3 active site. First, RING1 domains of HHARI and RNF144 promote open E2~Ubs. Second, we identify a Ub‐binding site on HHARI RING2 important for its recruitment to RING1‐bound E2~Ub. Mutations that ablate Ub binding to HHARI RING2 also decrease RBR ligase activity, consistent with RING2 recruitment being a critical step for the RBR Ub transfer mechanism. Finally, we demonstrate that the mechanism defined here is utilized by a variety of RBRs.
MEC-10 and MEC-19 Reduce the Neurotoxicity of the MEC-4(d) DEG/ENaC Channel inCaenorhabditis elegans
Authors: Chen Yushu , Bharill Shashank , O’Hagan Robert , Isacoff Ehud Y , Chalfie Martin
Published: June 2016

The Caenorhabditis elegans DEG/ENaC proteins MEC-4 and MEC-10 transduce gentle touch in the six touch receptor neurons . Gain-of-function mutations of mec-4 and mec-4(d) result in a hyperactive channel and neurodegeneration in vivo. Loss of MEC-6, a putative DEG/ENaC-specific chaperone, and of the similar protein POML-1 suppresses the neurodegeneration caused by a mec-4(d) mutation. We find that mutation of two genes, mec-10 and a new gene mec-19 (previously named C49G9.1), prevents this action of POML-1, allowing the touch receptor neurons to die in poml-1mec-4(d) animals. The proteins encoded by these genes normally inhibit mec-4(d) neurotoxicity through different mechanisms. MEC-10, a subunit of the mechanosensory transduction channel with MEC-4, inhibits MEC-4(d) activity without affecting MEC-4 expression. In contrast, MEC-19, a membrane protein specific to nematodes, inhibits MEC-4(d) activity and reduces MEC-4 surface expression.
Haplotag: Software for Haplotype-Based Genotyping-by-Sequencing Analysis
Authors: Tinker Nicholas A , Bekele Wubishet A , Hattori Jiro
Published: June 2016

Genotyping-by-sequencing (GBS), and related methods, are based on high-throughput short-read sequencing of genomic complexity reductions followed by discovery of single nucleotide polymorphisms (SNPs) within sequence tags. This provides a powerful and economical approach to whole-genome genotyping, facilitating applications in genomics, diversity analysis, and molecular breeding. However, due to the complexity of analyzing large data sets, applications of GBS may require substantial time, expertise, and computational resources. Haplotag, the novel GBS software described here, is freely available, and operates with minimal user-investment on widely available computer platforms. Haplotag is unique in fulfilling the following set of criteria: (1) operates without a reference genome; (2) can be used in a polyploid species; (3) provides a discovery mode, and a production mode; (4) discovers polymorphisms based on a model of tag-level haplotypes within sequenced tags; (5) reports SNPs as well as haplotype-based genotypes; and (6) provides an intuitive visual “passport” for each inferred locus. Haplotag is optimized for use in a self-pollinating plant species.
The Arabidopsis Auxin Receptor F-Box Proteins AFB4 and AFB5 Are Required for Response to the Synthetic Auxin Picloram
Authors: Prigge Michael J , Greenham Kathleen , Zhang Yi , Santner Aaron , Castillejo Cristina , Mutka Andrew M , O’Malley Ronan C , Ecker Joseph R , Kunkel Barbara N , Estelle Mark
Published: June 2016

The plant hormone auxin is perceived by a family of F-box proteins called the TIR1/AFBs. Phylogenetic studies reveal that these proteins fall into four clades in flowering plants called TIR1, AFB2, AFB4, and AFB6. Genetic studies indicate that members of the TIR1 and AFB2 groups act as positive regulators of auxin signaling by promoting the degradation of the Aux/IAA transcriptional repressors. In this report, we demonstrate that both AFB4 and AFB5 also function as auxin receptors based on in vitro assays. We also provide genetic evidence that AFB4 and AFB5 are targets of the picloram family of auxinic herbicides in addition to indole-3-acetic acid. In contrast to previous studies we find that null afb4 alleles do not exhibit obvious defects in seedling morphology or auxin hypersensitivity. We conclude that AFB4 and AFB5 act in a similar fashion to other members of the family but exhibit a distinct auxin specificity.
A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation inCaenorhabditis elegans
Authors: Neal Scott J , Park JiSoo , DiTirro Danielle , Yoon Jason , Shibuya Mayumi , Choi Woochan , Schroeder Frank C , Butcher Rebecca A , Kim Kyuhyung , Sengupta Piali
Published: June 2016

Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer) mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation.
A High-Density SNP Genetic Linkage Map and QTL Analysis of Growth-Related Traits in a Hybrid Family of Oysters (Crassostrea gigas × Crassostrea angulata) Using Genotyping-by-Sequencing
Authors: Wang Jinpeng , Li Li , Zhang Guofan
Published: June 2016

Oysters are among the most important species in global aquaculture. Crassostrea gigas, and its subspecies C. angulata, are the major cultured species. To determine the genetic basis of growth-related traits in oysters, we constructed a second-generation linkage map from 3367 single-nucleotide polymorphisms (SNPs) based on genotyping-by-sequencing, genotyped from a C. gigas × C. angulata hybrid family. These 3367 SNPs were distributed on 1695 markers, which were assigned to 10 linkage groups. The genetic linkage map had a total length of 1084.3 cM, with an average of 0.8 cM between markers; it thus represents the densest genetic map constructed for oysters to date. Twenty-seven quantitative trait loci (QTL) for five growth-related traits were detected. These QTL could explain 4.2–7.7% (mean = 5.4%) of the phenotypic variation. In total, 50.8% of phenotypic variance for shell width, 7.7% for mass weight, and 34.1% for soft tissue weight were explained. The detected QTL were distributed among eight linkage groups, and more than half (16) were concentrated within narrow regions in their respective linkage groups. Thirty-eight annotated genes were identified within the QTL regions, two of which are key genes for carbohydrate metabolism. Other genes were found to participate in assembly and regulation of the actin cytoskeleton, signal transduction, and regulation of cell differentiation and development. The newly developed high-density genetic map, and the QTL and candidate genes identified provide a valuable genetic resource and a basis for marker-assisted selection for C. gigas and C. angulata.
Synthetic Ligands of Cannabinoid Receptors Affect Dauer Formation in the NematodeCaenorhabditis elegans
Authors: Reis Rodrigues Pedro , Kaul Tiffany K , Ho Jo-Hao , Lucanic Mark , Burkewitz Kristopher , Mair William B , Held Jason M , Bohn Laura M , Gill Matthew S
Published: June 2016

Under adverse environmental conditions the nematode Caenorhabditis elegans can enter an alternate developmental stage called the dauer larva. To identify lipophilic signaling molecules that influence this process, we screened a library of bioactive lipids and found that AM251, an antagonist of the human cannabinoid (CB) receptor, suppresses dauer entry in daf-2 insulin receptor mutants. AM251 acted synergistically with glucose supplementation indicating that the metabolic status of the animal influenced the activity of this compound. Similarly, loss of function mutations in the energy-sensing AMP-activated kinase subunit, aak-2, enhanced the dauer-suppressing effects of AM251, while constitutive activation of aak-2 in neurons was sufficient to inhibit AM251 activity. Chemical epistasis experiments indicated that AM251 acts via G-protein signaling and requires the TGF-β ligand DAF-7, the insulin peptides DAF-28 and INS-6, and a functional ASI neuron to promote reproductive growth. AM251 also required the presence of the SER-5 serotonin receptor, but in vitro experiments suggest that this may not be via a direct interaction. Interestingly, we found that other antagonists of mammalian CB receptors also suppress dauer entry, while the nonselective CB receptor agonist, O-2545, not only inhibited the activity of AM251, but also was able to promote dauer entry when administered alone. Since worms do not have obvious orthologs of CB receptors, the effects of synthetic CBs on neuroendocrine signaling in C. elegans are likely to be mediated via another, as yet unknown, receptor mechanism. However, we cannot exclude the existence of a noncanonical CB receptor in C. elegans.
Patterns of Genome-Wide Variation inGlossina fuscipes fuscipesTsetse Flies from Uganda
Authors: Gloria-Soria Andrea , Dunn W Augustine , Telleria Erich L , Evans Benjamin R , Okedi Loyce , Echodu Richard , Warren Wesley C , Montague Michael J , Aksoy Serap , Caccone Adalgisa
Published: June 2016

The tsetse fly Glossina fuscipes fuscipes (Gff) is the insect vector of the two forms of Human African Trypanosomiasis (HAT) that exist in Uganda. Understanding Gff population dynamics, and the underlying genetics of epidemiologically relevant phenotypes is key to reducing disease transmission. Using ddRAD sequence technology, complemented with whole-genome sequencing, we developed a panel of ∼73,000 single-nucleotide polymorphisms (SNPs) distributed across the Gff genome that can be used for population genomics and to perform genome-wide-association studies. We used these markers to estimate genomic patterns of linkage disequilibrium (LD) in Gff, and used the information, in combination with outlier-locus detection tests, to identify candidate regions of the genome under selection. LD in individual populations decays to half of its maximum value (r2max/2) between 1359 and 2429 bp. The overall LD estimated for the species reaches r2max/2 at 708 bp, an order of magnitude slower than in Drosophila. Using 53 infected (Trypanosoma spp.) and uninfected flies from four genetically distinct Ugandan populations adapted to different environmental conditions, we were able to identify SNPs associated with the infection status of the fly and local environmental adaptation. The extent of LD in Gff likely facilitated the detection of loci under selection, despite the small sample size. Furthermore, it is probable that LD in the regions identified is much higher than the average genomic LD due to strong selection. Our results show that even modest sample sizes can reveal significant genetic associations in this species, which has implications for future studies given the difficulties of collecting field specimens with contrasting phenotypes for association analysis.
The Immature Fiber Mutant Phenotype of Cotton (Gossypium hirsutum) Is Linked to a 22-bp Frame-Shift Deletion in a Mitochondria Targeted Pentatricopeptide Repeat Gene
Authors: Thyssen Gregory N , Fang David D , Zeng Linghe , Song Xianliang , Delhom Christopher D , Condon Tracy L , Li Ping , Kim Hee Jin
Published: June 2016

Cotton seed trichomes are the most important source of natural fibers globally. The major fiber thickness properties influence the price of the raw material, and the quality of the finished product. The recessive immature fiber (im) gene reduces the degree of fiber cell wall thickening by a process that was previously shown to involve mitochondrial function in allotetraploid Gossypium hirsutum. Here, we present the fine genetic mapping of the im locus, gene expression analysis of annotated proteins near the locus, and association analysis of the linked markers. Mapping-by-sequencing identified a 22-bp deletion in a pentatricopeptide repeat (PPR) gene that is completely linked to the immature fiber phenotype in 2837 F2 plants, and is absent from all 163 cultivated varieties tested, although other closely linked marker polymorphisms are prevalent in the diversity panel. This frame-shift mutation results in a transcript with two long open reading frames: one containing the N-terminal transit peptide that targets mitochondria, the other containing only the RNA-binding PPR domains, suggesting that a functional PPR protein cannot be targeted to mitochondria in the im mutant. Taken together, these results suggest that PPR gene Gh_A03G0489 is involved in the cotton fiber wall thickening process, and is a promising candidate gene at the im locus. Our findings expand our understanding of the molecular mechanisms that modulate cotton fiber fineness and maturity, and may facilitate the development of cotton varieties with superior fiber attributes.
Multi-Population Selective Genotyping to Identify Soybean [Glycine max(L.) Merr.] Seed Protein and Oil QTLs
Authors: Phansak Piyaporn , Soonsuwon Watcharin , Hyten David L , Song Qijian , Cregan Perry B , Graef George L , Specht James E
Published: June 2016

Plant breeders continually generate ever-higher yielding cultivars, but also want to improve seed constituent value, which is mainly protein and oil, in soybean [Glycine max (L.) Merr.]. Identification of genetic loci governing those two traits would facilitate that effort. Though genome-wide association offers one such approach, selective genotyping of multiple biparental populations offers a complementary alternative, and was evaluated here, using 48 F2:3 populations (n = ∼224 plants) created by mating 48 high protein germplasm accessions to cultivars of similar maturity, but with normal seed protein content. All F2:3 progeny were phenotyped for seed protein and oil, but only 22 high and 22 low extreme progeny in each F2:3 phenotypic distribution were genotyped with a 1536-SNP chip (ca. 450 bimorphic SNPs detected per mating). A significant quantitative trait locus (QTL) on one or more chromosomes was detected for protein in 35 (73%), and for oil in 25 (52%), of the 48 matings, and these QTL exhibited additive effects of ≥ 4 g kg–1 and R2 values of 0.07 or more. These results demonstrated that a multiple-population selective genotyping strategy, when focused on matings between parental phenotype extremes, can be used successfully to identify germplasm accessions possessing large-effect QTL alleles. Such accessions would be of interest to breeders to serve as parental donors of those alleles in cultivar development programs, though 17 of the 48 accessions were not unique in terms of SNP genotype, indicating that diversity among high protein accessions in the germplasm collection is less than what might ordinarily be assumed.