bluuebunny/crossref_metadata_2025 huggingface dataset:
What Are the Experiences and Training Needs of Home-Based Carers in Dealing With Diabetes in a Rural Village in South Africa? An Explorative Study
Authors: Bopape Mamare A. , Mothiba Tebogo. M. , Bastiaens Hilde
Published: February 2019

Type 2 Diabetes Mellitus is a difficult chronic condition associated with morbidity, mortality and loss of quality of life. In Sub-Saharan African countries, HBC (Home-Based Carers) play an important role in the care of people diagnosed with chronic illnesses like diabetes. However, home-based carers seem to lack knowledge to care of people with diabetes because they have not been not formally trained. The aim of this study is to explore and describe the practices, knowledge and learning needs of Home-Based Carers (HBCs) of people with diabetes. A qualitative explorative approach was taken, holding interviews with 15 HBCs at the 4 clinics in the Ga-Dikgale village. The purposive sampling method was used to select participants for this study. Four themes are described: activities performed by HBCs during the care of diabetes patients, existing structures and sources of information for HBCs on the management of diabetic patients, challenges experienced by HBCs during the provision of care to diabetes patients and the learning needs of HBCs, based on how they want their training to be organised. HBCs execute various activities during the care of PWD (patients with diabetes) including providing nutritional advice, medication support, helping with household chores, accompanying patients to healthcare services and dressing their wounds. However, they lack knowledge of issues related to the care of PWD, which makes their role very difficult and challenging.
Iterative Approaches to Handling Heteroscedasticity With Partially Known Error Variances
Authors: Marzjarani Morteza
Published: February 2019

Heteroscedasticity plays an important role in data analysis. In this article, this issue along with a few different approaches for handling heteroscedasticity are presented. First, an iterative weighted least square (IRLS) and an iterative feasible generalized least square (IFGLS) are deployed and proper weights for reducing heteroscedasticity are determined. Next, a new approach for handling heteroscedasticity is introduced. In this approach, through fitting a multiple linear regression (MLR) model or a general linear model (GLM) to a sufficiently large data set, the data is divided into two parts through the inspection of the residuals based on the results of testing for heteroscedasticity, or via simulations. The first part contains the records where the absolute values of the residuals could be assumed small enough to the point that heteroscedasticity would be ignorable. Under this assumption, the error variances are small and close to their neighboring points. Such error variances could be assumed known (but, not necessarily equal).The second or the remaining portion of the said data is categorized as heteroscedastic. Through real data sets, it is concluded that this approach reduces the number of unusual (such as influential) data points suggested for further inspection and more importantly, it will lowers the root MSE (RMSE) resulting in a more robust set of parameter estimates.
On the Dynamic of Country Development
Authors: Rakotoarivelo Onialisoa Mirana , Ravelonirina Hanitriniaina Sammy Grégoire
Published: February 2019

In this work, we study the dynamics of the development of a country P. We find that this dynamic is governed by forces called development forces. There are three different types: natural force, exterior force, and interior force of development. They all have three components: human, economic and political. Depending on the intensity of these three forces, the resilience to natural and negative exterior forces, the level of development of P varies between two consecutive periods. This study allows us to conclude that development relies essentially on the interior force.
Monitoring and Evaluation on Effective Delivery of Social Studies for Improved Academic Performance
Authors: Loveth Chukwu, Chinyere , I. Mezieobi, Dan , Ejiofor Uguwanyi, Benedict , Chukwudi Okpoebo, Casmir
Published: February 2019

Monitoring and evaluation is very crucial in attaining targeted goals, especially in social studies. Social studies teacher mode of service delivery rub-off on the level of academic performance of students. It is very imperative that monitoring and evaluation mechanism be put in place to check how social studies lecturers in institutions of higher learning execute their lecture. In primary and secondary levels of education, the Ministry of education, from time to time send inspectors to schools to supervise the teaching and learning processes going on in schools. School heads are also mandated to supervise teaching and learning processes in their schools, this mechanism goes a long way to checkmate teachers’ excesses but this is lacking in institutions of higher learning, and appears to be responsible for the lackadaisical attitude to work by some lecturers. Such attitudes include absent from lecture, late coming to lecture among others. This paper therefore looked at the importance of monitoring and evaluation of teaching processes of social studies in higher institutions of learning, uses of monitoring and evaluation, among others and conclude that internal monitoring and evaluation team be established in higher institutions, to ensure adequate monitoring and evaluation of teaching and learning of social studies in institutions of higher learning for effective implementation of social studies contents among others.
Nitric Oxide and Oxidative Stress-Mediated Cardiovascular Functionality: From Molecular Mechanism to Cardiovascular Disease
Authors: He Weilue , Paula Kwesiga Maria , Gebreyesus Eyerusalem , Liu Sijia
Published: February 2019

The underlying pathology of most cardiovascular diseases (CVDs) such as coronary artery disease, high blood pressure, and stroke involves decreased cardiovascular contractility and anatomic alterations in cardiovascular structures. Nitric oxide (NO) regulates vascular tone and contractile function of myocardium and maintains blood vessel homeostasis. Interestingly, the effect of NO is like a double-edged sword in the body. Insufficient NO causes hypertension and atherosclerosis, while an overproduction of NO may foster inflammation and cause heart infarction and shock. In addition, growing evidences have shown that oxidative stress plays pivotal roles in the initiation and progression of CVDs. This chapter will discuss in detail the roles NO plays in the cardiovascular system under both physiological and pathological conditions. We will focus on: (1) the molecular mechanism of cardiovascular contraction, (2) NO/Ca2+-induced muscle relaxation, (3) NO-related structural change in blood vessels, and (4) redox balance in the cardiovascular system. The relationships between these molecular mechanisms and the characteristics of CVDs will be highlighted.
Longueur du mot et déficit accentuel: le cas de la clausule du trimètre et du choliambe
Authors: Borea Marco
Published: February 2019

Les mots longs sont rares à la clausule dutrimètre iambique grec. Leur longueur compense en quelquesorte le déficit accentuel qu’ils entraînent. Le choliambe,quant à lui, s’écarte de cette tendance et affectionne untype prosodique précis, le trisyllabe, en le dotant d’unepolymorphie accentuelle remarquable.Longs words seldom occur in the clausula ofthe iambic trimeter. Word length is offset by the accentualdeficiency they bring about. The choliambus, though, quitediverges from this tendency and show a preference for aspecific prosodic type, the trisyllable, which it provides witha relevant accentual polymorphism.
Algunas consideraciones para el estudio de la métrica española
Authors: Domínguez Caparrós José
Published: February 2019

En este trabajo se dan unas notas que quierenservir de prolegómeno para orientar a quien vaya a empezarel estudio de la métrica española. Se trata fundamentalmentede observaciones acerca de las clases de estudios de métrica,el carácter del verso español, su estructura y su relación conel verso europeo. A lo largo de la explicación se dan las referenciasde las obras esenciales para el conocimiento de laversificación española.In this work some notes that want to serve as aprelude to guide who is going to start the study of the Spanishmetrics are given. It is mainly about observations about theclasses of metrical studies, the character of the Spanishverse, its structure and its relation with the European verse.Throughout the explanation are given the references of theessential works for the knowledge of Spanish versification.
Endecasílabos fragmentados
Authors: Pardo Arcadio
Published: February 2019

El verso endecasílabo puede quedarfragmentado en dos, tres o más unidades por la inclusiónen su interior de uno o más incisos o fragmentos de variableextensión. Se observan también las distintas posiciones delos fragmentos en el verso.Hendecasyllables can be phrased as two,three or more units by inserting one or more digressions ofvarying length into the verse. The different positions theseinterpolations can occupy in the verse are also taken intoaccount.
Esteban Torre:"LXII Sonetos". Prólogo de M.ª Victoria Utrera Torremocha. Sevilla: Renacimiento, Colección Mediodía, 2018
Authors: Romero Luque Manuel
Published: February 2019

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Celebrating 7 Years and Counting! Continuing to Grow Our MTE Community
Authors: Crespo Sandra , Bieda Kristen
Published: February 2019

This editorial closes our 4-year tenure as editors of the MTE journal. Although time has surely flown, we have much to celebrate and to reflect on as we bid farewell to our editorial office. We have had the privilege and responsibility to continue the legacy of the founding editors (Peg Smith and Melissa Boston) and develop our vision for increasing the visibility and impact of this journal as well as to grow the diversity of perspectives, authors, and reviewers of the journal. With this editorial, we celebrate our journey, highlighting our top three accomplishments, and then outline top priorities for the journal as it moves forward under the editorship of the new incoming editors.
Ensino de Semiótica aplicada através da Aprendizagem Baseada em Projetos (PjBL): uma proposta metodológica
Authors:   Pontifícia Universidade Católica do Paraná - PUCPR, Maziero Lucia Teresinha Peixe
Published: February 2019

Este artigo discute a aprendizagem baseada em projetos – PjBL (Project-Based Learning), que se desenvolve sob o processo de obtenção de um produto final, a qual foi utilizada como metodologia norteadora da disciplina de semiótica aplicada no curso de Design de Moda. Apresentam-se aqui as ações de ensino por meio de aprendizagem ativa que levaram os estudantes à formulação do problema de pesquisa, às análises e resultados, e a escrita de um artigo com potencial de publicação científica. Como objeto de estudo para a pesquisa foram analisadas publicidades de joias, veiculadas em revista de moda, analisadas por meio de duas vertentes semióticas: Peirce e Greimas.
Design e Filosofia: Formação de um grupo de estudo como prática pedagógica
Authors:   Universidade Anhembi Morumbi, Barbosa Carlos Alberto
Published: February 2019

Este artigo apresenta o relato de uma experiência de formação do Grupo de Estudo Design e Filosofia, constituído por alunas do curso de bacharelado em Design de Moda da Universidade Anhembi Morumbi. A formação desse grupo, e a proposta de projeto derivada de suas discussões, permitiu ainda uma reflexão acerca da importância da formação cultural dos alunos de cursos superiores, e como um olhar para o horizonte de práticas interdisciplinares e transdisciplinar permite reestabelecer a relação entre o objeto de estudo e a reflexão. Durante o ano em que foi possível acompanhar o desenvolvimento dessa experiência pedagógica, foi notado que as alunas de fato assumiram a posição de protagonistas diante das demandas de leituras e sugestões de projetos, o que instigou a busca de conteúdos e de soluções para problemas envolvendo diferentes especialidades do design, notadamente o design de moda e o design digital.
Mapas mentais e painéis de imagem: o estudo semiológico na definição do conceito em Moda
Authors: Pereira Camila Konradt , Ruthschilling Anne Anicet
Published: February 2019

Este trabalho apresenta uma proposta metodológica para o desenvolvimento de mapas mentais e painéis de imagens a partir da leitura da análise semiológica saussuriana e de metodologias projetuais. O problema deste artigo surge da inserção de conteúdos teóricos em disciplinas de projeto e da necessidade de dinâmicas que permitam a construção conjunta de conhecimentos, além da elaboração do projeto com base em uma aprendizagem significativa. Para tanto, buscou-se aliar o estudo da semiologia à utilização de mapas mentais em metodologias de design com vistas à definição de parâmetros para a formulação do conceito do projeto. Como resultado, apresentamos a aplicação das etapas de desenvolvimento identificadas no estudo para a geração do conceito e das imagens inspiracionais de uma coleção por estudantes de projeto de moda de um curso de graduação em Design de Moda de uma faculdade privada do Brasil.
Educar para reconocer:
Authors: Rodríguez Almansa Andrés , Costa Casais Manuela , López Facal Ramón
Published: February 2019

Una de las singularidades del paisaje costero de Galicia es la amplia presencia de depósitos edafo-sedimentarios cuaternarios, de extraordinaria calidad en cuanto a la información que aportan. Una diferencia respecto al ámbito atlántico europeo. Registran la memoria de la tierra y pueden contemplarse como archivos que documentan cambios paleo-ambientales a escala local, regional y global y contextos geomorfológicos relacionados con la historia humana.

Imbuido por una renovada concepción del patrimonio, que valora las formaciones naturales más allá de su apreciación estética, el pensamiento científico ha comenzado a considerar estos depósitos como un bien patrimonial. Sin embargo, se produce una total desconexión entre estas aspiraciones y el reconocimiento de administración y ciudadanía.

Desde la convicción de que solo se producirá un reajuste a través de una educación generadora de conciencia social sobre los paisajes geomorfológicos, en este trabajo se plantea la relevancia de una educación patrimonial de índole crítica; se propone un modelo de actuación focalizado en la formación inicial del profesorado y se avanzan algunos datos que muestren sus resultados

One of the distinctive features of the coastal landscape of Galicia is its great number of quaternary pedosedimentary deposits, which are of extraordinary quality in terms of the information which, they provide, making them stand out from the rest of the European Atlantic coast. They record the memory of the land and can be considered to be repositories documenting paleoenvironmental changes on local, regional and global levels, as well as geomorphological contexts related with human history.

Imbued with a renewed understanding of heritage, which values natural formations beyond the appreciation of their aesthetic aspect, scientific thinking has begun to consider these deposits as cultural assets. However, a total disconnection arises between these aspirations and the recognition of such assets by the political administration and citizens.

In the belief that a change in this situation will only be brought about via an education which generates a social conscience regarding geomorphological landscapes, this study examines the relevance of a form of heritage education which is critical in nature; an approach focused on initial teacher training is proposed and data showing the results of this approach are presented.
Investigación de impacto sobre la formación en mediación y educación en museos: análisis de la Web of Science
Authors: Alvarez-Rodríguez Dolores , Marfil-Carmona Rafael , Báez-García Cinta
Published: February 2019

La mediación educativa en el ámbito de la Educación No Formal y de las industrias culturales es, cada vez más importante, especialmente a la hora de llegar con eficacia a los públicos y la ciudadanía por parte de las instituciones vinculadas al patrimonio, el arte y la creatividad. De forma específica, los museos requieren de una formación y capacitación en la función mediadora y educativa. Este trabajo, basado en una revisión bibliográfica de artículos en revistas de impacto, analiza las publicaciones científicas en la Web of Science (WOS) vinculadas a la formación de educadores en museos. El análisis cuantitativo y cualitativo de las características principales de estos contenidos nos lleva a afirmar que la educación en museos y patrimonio es una línea emergente de investigación, aunque se trata de un sector en el que existen dificultades para trasladar al mundo académico e investigador la riqueza y diversidad de la educación en museos. En concreto, la WOS no cuenta con un contenido destacado en la temática general de mediación en museos y, particularmente, de la formación de ese colectivo profesional. En la selección final de 51 artículos, las publicaciones procedentes de universidades o instituciones españolas tienen un peso destacado. En resumen, es imprescindible apostar por la presencia de la realidad profesional de los museos en los circuitos de investigación, mejorando la reflexión y el análisis sobre la preparación y capacitación de estos profesionales.

Educational mediation in non-formal education and cultural industries contexts is increasingly important, especially when institutions of heritage, art and creativity try to reach effectively the public and citizenship. Specifically, museums require training and instruction in mediation and the educational role. This work, based on a bibliographic review of articles in impact journals, analyses the scientific publications on the Web of Science (WOS) linked to the training of educators in museums. The quantitative and qualitative analysis of the main characteristics of these contents leads us to affirm that education on museums and heritage is an emerging line of research. Although it is a sector in which there are some difficulties translating the richness and diversity of education in museums to the academic and researcher world. In particular, the WOS does not have a prominent content in the general theme of mediation in museums and, in particular, the training of these professionals. In the final 51 articles selected, the publications coming from Spanish universities or institutions have an outstanding weight. In summary, it is necessary to support the presence of the professional reality of museums in academic research circuits, improving reflection and analysis on the preparation and training of these professionals.
Patrimonio, curriculum y formación del profesorado de Educación Primaria en México
Authors: Luna Úrsula , Vicent Naiara , Reyes Cabrera William , Quiñonez Pech Sergio Humberto
Published: February 2019

Este trabajo busca conocer cuál es la presencia del patrimonio en el curriculum de Educación Primaria en México, para posteriormente analizar su incidencia en los programas y planes de estudio de la formación del profesorado de esta etapa. Para ello, se ha llevado a cabo un análisis de contenidos para la identificación y categorización de una serie de términos vinculados al patrimonio. Posteriormente, se ha realizado un análisis de frecuencias de estos términos tanto en la ley educativa vigente en México como en los planes de estudio de las licenciaturas de Educación Primaria. Por último, se ha analizado la correspondencia entre la presencia del patrimonio en el curriculum mexicano de Educación Primaria y los planes formativos de los futuros maestros. Los resultados muestran mayor presencia del patrimonio en el curriculum de Educación Básica, y una mayor correspondencia entre los contenidos de éste y la Licenciatura de Educación Primaria Intercultural Bilingüe. Además, la presencia de términos tradicionales es mayor en áreas como historia y artes, mientras que otros como identidad o tradición se presentan en áreas como la de lengua.

This work aims at getting to know which the presence of heritage in the Elementary Education curriculum in Mexico is, to ultimately analyze its impact in the programs and syllabuses in the formation of teachers at this stage. For this purpose, an analysis of contents has been carried out so as to identify and categorize a series of terms linked to heritage. Afterwards, an analysis of the frequency of use of these terms has been carried out, not only in the Education Law in force in Mexico, but also in the syllabuses of the degrees for Elementary Education. Lastly, a final analysis has been done regarding the correspondence between the presence of heritage in the curriculums and its presence in the formative plans for future Elementary School teachers. The results portray a greater presence of heritage in the Basic Education curriculum, and a bigger correspondence between its contents and that of the Intercultural Bilingual Primary Education Degree. On top of that, the presence of traditional terms is bigger in areas such as History and Art, whereas other terms such as identity or tradition are more prominent in areas such as Language.
«LA LETRA… POR LA VISTA ENTRA». A PROPÓSITO DE LA NUEVA NORMATIVA SOBRE EL USO DE LAS MAYÚSCULAS Y SU APLICACIÓN EN LOS TEXTOS DE ENSEÑANZA
Authors: Ricós Vidal Amparo , García Valle Adela
Published: February 2019

El propósito de este artículo consiste en analizar el uso de las mayúsculas en una serie de manuales posteriores a 2010 y determinar los aspectos que plantean mayores problemas u ofrecen diferentes soluciones, con la finalidad última de divulgar los aspectos pendientes de una mejor regulación, hacer hincapié en la importancia de criterios claros en la aplicación práctica de las normas y en la responsabilidad de los profesionales del sector editorial, puesto que en la adquisición y aprendizaje de la ortografía es fundamental la memoria visual. El análisis muestra que las mayores dificultades se hallan en la función identificativa de las mayúsculas y se centran en los aspectos más novedosos y con mayor repercusión social (tratamientos, títulos o cargos). La causa de estos errores se puede explicar por la densidad y complejidad de la obra académica, que no favorece su consulta, y por la necesidad de conocimientos extralingüísticos en algunas opciones, no siempre al alcance de un público medio no experto. Por último, si bien se señala la responsabilidad de muchas de las editoriales en la salvaguarda de las normas ortográficas, cabe insistir en la necesidad de directrices claras en los libros de estilo de las editoriales para evitar soluciones diversas en un mismo manual, además de un mayor cuidado en las reediciones de los textos, entre otras cuestiones.
Comparative study on the composition of four different varieties of garlic
Authors: Chen Cun , Cai Jing , Liu Song-qing , Qiu Guo-liang , Wu Xiao-gang , Zhang Wei , Chen Cheng , Qi Wei-liang , Wu Yong , Liu Zhi-bin
Published: February 2019

Garlic is used as a medicinal seasoning worldwide. The aim of this work was to compare four varieties of garlic: ‘Taicangbaipi’, ‘Ershuizao’, ‘Hongqixing’, and ‘Single-clove’; among them, ‘Ershuizao’ and ‘Hongqixing’ are unique to the Sichuan Province of China. Firstly, soluble sugar, starch, and the protein content of the garlic were analysed. There was more soluble sugar in ‘Single-clove’, total starch in ‘Hongqixing’, and protein content in ‘Ershuizao’ relative to the other three varieties, respectively. Gas chromatography–mass spectrometry analysis showed that ‘Ershuizao’ and ‘Hongqixing’ contained high levels of 5-hydroxymethylfurfural, which has antitumor, antioxidant, and cytoprotective effects. Indeed, the extracts from these two types of garlic were more effective at inhibiting tumour growth than that from the others. Moreover, the sulphide content and antimicrobial effects of ‘Ershuizao’ and ‘Hongqixing’ garlic were also higher than those of the other two types of garlic. In addition, changes observed in the membrane permeability and protein leakage suggest that the antimicrobial activity of the ‘Ershuizao’ and ‘Hongqixing’ extracts may be due to the destruction of the structural integrity of the cell membranes, leading to cell death.
Moisture Absorption Behaviour, Extract Yields and Sensory Evaluation of Soaked Cyperus esculentus
Authors: Elutade Olayinka O. , Oyawoye Olubukola M. , Agbo Ediga B.
Published: February 2019

This work investigated the comparison in the moisture absorption behavior, the extract yields and sensory evaluation of brown and yellow varieties of tiger nut (Cyperus esculentus) tubers when soaked in water for tiger nut beverage production. For each tuber variety, 3 g of it was steeped in 30 ml of distilled water for 5 days and periodically re-weighed at 24-hour intervals until the tubers had attained saturated moisture content. Furthermore, 200 g of each variety was steeped in 800 ml of sterile distilled water for periods of 0 hour (control), 24 hours, 48 hours and 96 hours, respectively. At the end of each time interval, the tubers were removed, ground in 800 ml sterile distilled water, sieved, and the beverage liquid filtrate obtained measured as the percentage extract yield for the tuber sample. Aroma, colour, taste and acceptance were the parameters used for sensory evaluation. The brown tubers showed a significantly (P≤0.05) higher moisture absorption behavior than the yellow tubers; the brown and yellow had the highest rate of moisture absorption ability of 52.22% and 35.56%, respectively, occurring after soaking for 24 hours. At same 24 hours of the soaking period, the resultant extracts obtained from the brown and yellow tubers were at a significant peak yields of 92% and 89.5%, respectively. Extracts from the brown tubers were preferred in taste and colour to those from the yellow variety. Water absorption potentials of tiger nut tubers during soaking process, has potential effects on the beverage extraction and quality.
Estimation and Assessment of Soil Erosion Risk of Nun Watershed Using Remote Sensing and GIS
Authors: Kale V. B.
Published: February 2019

This study aims to investigate the soil erosion from selected watershed from Dehradun area having hilly terrain and human’s development activities The remote sensing based model was decided to perform the estimations and assessment of soil eroded from watershed. The Nun river watershed was selected for study. From the estimated quantity of soil eroded we can predict the risk due degraded soil in terms of decreasing crop productivity. The present study assists to decide the optimum land use for specific purpose at the Nun watershed in Deharadun, Uttarakhand. The major objective of the study is to assess the soil erosion risk in the study area.
Synergetic Functional Nanocomposites Enhance Immunotherapy in Solid Tumors by Remodeling the Immunoenvironment
Authors: Yang Linnan , Sun Jing , Liu Qiang , Zhu Rongrong , Yang Qiannan , Hua Jiahui , Zheng Longpo , Li Kun , Wang Shilong , Li Ang
Published: February 2019

Checkpoint blockade immunotherapy has demonstrated significant clinical success in various malignant tumors. However, the therapeutic response is limited due to the immunosuppressive tumor microenvironment (ITM). In this study, a functional nanomaterial, layered double hydroxides (LDHs), carrying specific functional miR155 is developed to modulate ITM by synergistically repolarizing tumor associated macrophages (TAMs) to M1 subtype. LDH nanoparticles loaded with miR155 (LDH@155) exhibit superior ability in cellular uptake by murine macrophages, miR escape into the cytoplasm and TAMs specific delivery when introtumoral administration. Meanwhile, upon exposure to LDH@155, TAMs are significantly skewed to M1 subtype, which markedly inhibits myeloid‐derived suppressor cells (MDSCs) formation and stimulates T‐lymphocytes to secrete more interferon‐γ (IFN‐γ) cytokines in vitro. Introtumoral administration of LDH@155 reduces the percentage of TAMs and MDSCs in the tumor and elevates CD4+ and CD8+ T cell infiltration and activation, which can promote therapeutic efficiency of α‐PD‐1 antibody immunotherapy. Furthermore, it is found that LDH@155 significantly decreases the expression level of phosphorylated STAT3 and ERK1/2 and activates NF‐κB expression in TAMs, indicating that the STAT3, ERK1/2, and NF‐κB signaling pathways may involve in LDH@155‐induced macrophage polarization. Overall, the results suggest that LDH@155 nanoparticles may, in the future, function as a promising agent for cancer combinational immunotherapy.
Circle of Willis variations in migraine patients with ischemic stroke
Authors: Hamming Arend M. , van Walderveen Marianne A. A. , Mulder Inge A. , van der Schaaf Irene C. , Kappelle L. Jaap , Velthuis Birgitta K. , Ferrari Michel D. , Terwindt Gisela M. , Visser Marieke C. , Schonewille Wouter , Algra Ale , Wermer Marieke J. H. ,   the Dutch acute Stroke Study (DUST) investigators
Published: February 2019

Objectives

Migraine is a risk factor for stroke, which might be explained by a higher prevalence in anatomical variants in the circle of Willis (CoW). Here, we compared the presence of CoW variants in patients with stroke with and without migraine.

Materials and Methods

Participants were recruited from the prospective Dutch acute Stroke Study. All participants underwent CT angiography on admission. Lifetime migraine history was assessed with a screening questionnaire and confirmed by an interview based on International Classification of Headache Disorders criteria. The CoW was assessed for incompleteness/hypoplasia (any segment <1 mm), for anterior cerebral artery asymmetry (difference > 1/3), and for posterior communicating artery (Pcom) dominance (Pcom–P1 difference > 1/3). Odds ratios with adjustments for age and sex (aOR) were calculated with logistic regression.

Results

We included 646 participants with stroke, of whom 52 had a history of migraine. Of these, 45 (87%) had an incomplete or hypoplastic CoW versus 506 (85%) of the 594 participants without migraine (aOR: 1.47; 95% CI: 0.63–3.44). There were no differences between participants with and without migraine in variations of the anterior or posterior CoW, anterior cerebral artery asymmetry (aOR: 0.86; 95% CI: 0.43–1.74), or Pcom dominance (aOR: 0.64; 95% CI: 0.32–1.30). There were no differences in CoW variations between migraine patients with or without aura.

Conclusion

We found no significant difference in the completeness of the CoW in acute stroke patients with migraine compared to those without.
Incomplete estimates of genetic diversity within species: Implications for DNA barcoding
Authors: Phillips Jarrett D. , Gillis Daniel J. , Hanner Robert H.
Published: February 2019

DNA barcoding has greatly accelerated the pace of specimen identification to the species level, as well as species delineation. Whereas the application of DNA barcoding to the matching of unknown specimens to known species is straightforward, its use for species delimitation is more controversial, as species discovery hinges critically on present levels of haplotype diversity, as well as patterning of standing genetic variation that exists within and between species. Typical sample sizes for molecular biodiversity assessment using DNA barcodes range from 5 to 10 individuals per species. However, required levels that are necessary to fully gauge haplotype variation at the species level are presumed to be strongly taxon‐specific. Importantly, little attention has been paid to determining appropriate specimen sample sizes that are necessary to reveal the majority of intraspecific haplotype variation within any one species. In this paper, we present a brief outline of the current literature and methods on intraspecific sample size estimation for the assessment of COI DNA barcode haplotype sampling completeness. The importance of adequate sample sizes for studies of molecular biodiversity is stressed, with application to a variety of metazoan taxa, through reviewing foundational statistical and population genetic models, with specific application to ray‐finned fishes (Chordata: Actinopterygii). Finally, promising avenues for further research in this area are highlighted.
Contrasting effects of habitat discontinuity on three closely related fungivorous beetle species with diverging host‐use patterns and dispersal ability
Authors: Kobayashi Takuya , Sota Teiji
Published: February 2019

Understanding how landscape structure influences biodiversity patterns and ecological processes are essential in ecological research and conservation practices. Forest discontinuity is a primary driver affecting the population persistence and genetic structure of forest‐dwelling species. However, the actual impacts on populations are highly species‐specific. In this study, we tested whether dispersal capability and host specialization are associated with susceptibility to forest discontinuity using three closely related, sympatric fungivorous ciid beetle species (two host specialists, Octotemnus assimilis and O. crassus; one host generalist, O. kawanabei). Landscape genetic analyses and the estimation of effective migration surfaces (EEMS) method consistently demonstrated contrasting differences in the relationships between genetic structure and configuration of forest land cover. Octotemnus assimilis, one of the specialists with a presumably higher dispersal capability due to lower wing loading, lacked a definite spatial genetic structure in our study landscape. The remaining two species showed clear spatial genetic structure, but the results of landscape genetic analyses differed between the two species: while landscape resistance appeared to describe the spatial genetic structure of the specialist O. crassus, genetic differentiation of the generalist O. kawanabei was explained by geographic distance alone. This finding is consistent with the prediction that nonforest areas act more strongly as barriers between specialist populations. Our results suggest that differences in host range can influence the species‐specific resistance to habitat discontinuity among closely related species inhabiting the same landscape.
Can employee ownership and human resource management policies clash in worker cooperatives? Lessons from a defunct cooperative
Authors: Basterretxea Imanol , Heras‐Saizarbitoria Iñaki , Lertxundi Aitziber
Published: February 2019

The article analyzes the interaction between employee ownership, HRM policies and practices, and HRM outcomes in what was the world's biggest industrial worker cooperative for decades, and now defunct, Fagor Electrodomésticos. Using longitudinal internal data and detailed interviews with key stakeholders, this paper sheds light on how employee ownership conditioned HRM policies. HRM outcomes—such as job satisfaction and absenteeism—are also analyzed over a long period of time. Chronic nepotism when recruiting new members, failures in the training policy, impoverished and Taylorist working systems, and reverse dominance hierarchies are analyzed as factors that increased free riding and caused low satisfaction and the disengagement of working members. This case study contributes to the literature on HRM and worker cooperatives as it provides some insights that are rarely found in that literature. It also provides guidance to worker cooperatives about increasing the fit between employee ownership and HRM policies and outcomes.
Krill faecal pellets drive hidden pulses of particulate organic carbon in the marginal ice zone
Authors: Belcher A. , Henson S. A. , Manno C. , Hill S. L. , Atkinson A. , Thorpe S. E. , Fretwell P. , Ireland L. , Tarling G. A.
Published: February 2019

The biological carbon pump drives a flux of particulate organic carbon (POC) through the ocean and affects atmospheric levels of carbon dioxide. Short term, episodic flux events are hard to capture with current observational techniques and may thus be underrepresented in POC flux estimates. We model the potential hidden flux of POC originating from Antarctic krill, whose swarming behaviour could result in a major conduit of carbon to depth through their rapid exploitation of phytoplankton blooms and bulk egestion of rapidly sinking faecal pellets (FPs). Our model results suggest a seasonal krill FP export flux of 0.039 GT C across the Southern Ocean marginal ice zone, corresponding to 17–61% (mean 35%) of current satellite-derived export estimates for this zone. The magnitude of our conservatively estimated flux highlights the important role of large, swarming macrozooplankton in POC export and, the need to incorporate such processes more mechanistically to improve model projections.
A framework for tracer-based metabolism in mammalian cells by NMR
Authors: Saborano Raquel , Eraslan Zuhal , Roberts Jennie , Khanim Farhat L. , Lalor Patricia F. , Reed Michelle A. C. , Günther Ulrich L.
Published: February 2019

Metabolism changes extensively during the normal proliferation and differentiation of mammalian cells, and in cancer and inflammatory diseases. Since changes in the metabolic network reflect interactions between genetic, epigenetic and environmental changes, it is helpful to study the flow of label from isotopically labelled precursors into other metabolites rather than static metabolite levels. For this Nuclear Magnetic Resonance (NMR) spectroscopy is an attractive technique as it can quantify site-specific label incorporation. However, for applications using human cells and cell lines, the challenge is to optimize the process to maximize sensitivity and reproducibility. Here we present a new framework to analyze metabolism in mammalian cell lines and primary cells, covering the workflow from the preparation of cells to the acquisition and analysis of NMR spectra. We have applied this new approach in hematological and liver cancer cell lines and confirm the feasibility of tracer-based metabolism in primary liver cells.
Molecular evolution of influenza B virus during 2011–2017 in Chaoyang, Beijing, suggesting the free influenza vaccine policy
Authors: Lei Na , Wang Hai-bin , Zhang Yu-song , Zhao Jian-hong , Zhong Yi , Wang Yuan-jie , Huang Li-yong , Ma Jian-xin , Sun Qiang , Yang Lei , Shu Yue-long , Li Shu-ming , Sun Ling-li
Published: February 2019

Two influenza B virus lineages, B/Victoria and B/Yamagata, are co-circulating in human population. While the two lineages are serologically distinct and TIV only contain one lineage. It is important to investigate the epidemiological and evolutionary dynamics of two influenza B virus lineages in Beijing after the free influenza vaccine policy from 2007. Here, we collected the nasopharyngeal swabs of 12657 outpatients of influenza-like illness and subtyped by real-time RT-PCR during 2011–2017. The HA and NA genes of influenza B were fully sequenced. The prevalence is the highest in the 6–17 years old group among people infected with influenza B. Yamagata-lineage virus evolved to two inter-clade from 2011–2014 to 2014–2017. The amino acids substitutions of HA1 region were R279K in strains of 2011–2014 and L173Q, M252V in strains of 2014–2017. Substitutions L58P, I146V were observed in HA1 region of Victoria-lineage virus in 2011–2012 and I117V, N129D were showed in 2015–2017. Phylogenetic analysis of NA showed Yamagata-Victoria inter-lineage reassortant occurred in 2013–2014. Influenza B mainly infect the school-aged children in Beijing and the free influenza vaccine inoculation does not seem to block school-age children from infection with influenza B. The antigen characteristics of circulating influenza B were different to the recommended vaccine strains. We concluded that the Victoria-lineage vaccine strain should been changed and the free influenza vaccine should be revalued.
Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen
Authors: Ariza Márquez Yeimy Viviana , Briceño Ignacio , Aristizábal Fabio , Niño Luis Fernando , Yosa Reyes Juvenal
Published: February 2019

Breast cancer is a group of multigenic diseases. It is the most common cancer diagnosed among women worldwide and is often treated with tamoxifen. Tamoxifen is catalysed by cytochrome P450 2D6 (CYP2D6), and inter-individual variations in the enzyme due to single nucleotide polymorphisms (SNPs) could alter enzyme activity. We evaluated SNPs in patients from Colombia in South America who were receiving tamoxifen treatment for breast cancer. Allelic diversity in the CYP2D6 gene was found in the studied population, with two patients displaying the poor-metaboliser phenotype. Molecular dynamics and trajectory analyses were performed for CYP2D6 from these two patients, comparing it with the common allelic form (CYP2D6*1). Although we found no significant structural change in the protein, its dynamics differ significantly from those of CYP2D6*1, the effect of such differential dynamics resulting in an inefficient enzyme with serious implications for tamoxifen-treated patients, increasing the risk of disease relapse and ineffective treatment.
Translocation of promoter-conserved hatching enzyme genes with intron-loss provides a new insight in the role of retrocopy during teleostean evolution
Authors: Nagasawa Tatsuki , Kawaguchi Mari , Yano Tohru , Isoyama Sho , Yasumasu Shigeki , Okabe Masataka
Published: February 2019

The hatcing enzyme gene (HE) encodes a protease that is indispensable for the hatching process and is conserved during vertebrate evolution. During teleostean evolution, it is known that HE experienced a drastic transfiguration of gene structure, namely, losing all of its introns. However, these facts are contradiction with each other, since intron-less genes typically lose their original promoter because of duplication via mature mRNA, called retrocopy. Here, using a comparative genomic assay, we showed that HEs have changed their genomic location several times, with the evolutionary timings of these translocations being identical to those of intron-loss. We further showed that HEs maintain the promoter sequence upstream of them after translocation. Therefore, teleostean HEs are unique genes which have changed intra- (exon-intron) and extra-genomic structure (genomic loci) several times, although their indispensability for the reproductive process of hatching implies that HE genes are translocated by retrocopy with their promoter sequence.
Optimal design, anti-tumour efficacy and tolerability of anti-CXCR4 antibody drug conjugates
Authors: Costa Maria José , Kudaravalli Jyothirmayee , Ma Jing-Tyan , Ho Wei-Hsien , Delaria Kathy , Holz Charles , Stauffer Angela , Chunyk Allison Given , Zong Qing , Blasi Eileen , Buetow Bernard , Tran Thomas-Toan , Lindquist Kevin , Dorywalska Magdalena , Rajpal Arvind , Shelton David L. , Strop Pavel , Liu Shu-Hui
Published: February 2019

Antibody-drug conjugates (ADCs) are promising therapies for haematological cancers. Historically, their therapeutic benefit is due to ADC targeting of lineage-restricted antigens. TheC-X-Cmotif chemokinereceptor 4 (CXCR4) is attractive for targeted therapy of haematological cancers, given its expression in multiple tumour types and role in cancer “homing” to bone marrow. However, CXCR4 is also expressed in haematopoietic cells and other normal tissues, raising safety challenges to the development of anti-CXCR4 ADCs for cancer treatment. Here, we designed the first anti-CXCR4 ADC with favourable therapeutic index, effective in xenografts of haematopoietic cancers resistant to standard of care and anti-CXCR4 antibodies. We screened multiple ADC configurations, by varying type of linker-payload, drug-to-antibody ratio (DAR), affinity and Fc format. The optimal ADC bears a non-cleavable linker, auristatin as payload at DAR = 4 and a low affinity antibody with effector–reduced Fc. Contrary to other drugs targeting CXCR4, anti-CXCR4 ADCs effectively eliminated cancer cells as monotherapy, while minimizing leucocytosis. The optimal ADC selectively eliminated CXCR4+cancer cells in solid tumours, but showed limited toxicity to normal CXCR4+tissues, sparing haematopoietic stem cells and progenitors. Our work provides proof-of-concept that through empirical ADC design, it is possible to target proteins with broad normal tissue expression.
Discovery of ((1,2,4-oxadiazol-5-yl)pyrrolidin-3-yl)ureidyl derivatives as selective non-steroidal agonists of the G-protein coupled bile acid receptor-1
Authors: Di Leva Francesco Saverio , Festa Carmen , Carino Adriana , De Marino Simona , Marchianò Silvia , Di Marino Daniele , Finamore Claudia , Monti Maria Chiara , Zampella Angela , Fiorucci Stefano , Limongelli Vittorio
Published: February 2019

The G-protein bile acid receptor 1 (GPBAR1) has emerged in the last decade as prominent target for the treatment of metabolic and inflammatory diseases including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. To date numerous bile acid derivatives have been identified as GPBAR1 agonists, however their clinical application is hampered by the lack of selectivity toward the other bile acid receptors. Therefore, non-steroidal GPBAR1 ligands able to selectively activate the receptor are urgently needed. With this aim, we here designed, synthesized and biologically evaluated ((1,2,4-oxadiazol-5-yl)pyrrolidin-3-yl) urea derivatives as novel potent GPBAR1 agonists. Particularly, compounds 9 and 10 induce the mRNA expression of the GPBAR1 target gene pro-glucagon and show high selectivity over the other bile acid receptors FXR, LXRα, LXRβ and PXR, and the related receptors PPARα and PPARγ. Computational studies elucidated the binding mode of 10 to GPBAR1, providing important structural insights for the design of non-steroidal GPBAR1 agonists. The pharmacokinetic properties of 9 and 10 suggest that the ((1,2,4-oxadiazol-5-yl)pyrrolidin-3-yl)ureydil scaffold might be exploited to achieve effective drug candidates to treat GPBAR1 related disorders.
Slight changes in the chemical structure of haemanthamine greatly influence the effect of the derivatives on rumen fermentation in vitro
Authors: Ramos-Morales Eva , Tibble-Howlings Jamie , Lyons Laura , Ogbu Magnus O. , Murphy Patrick J. , Braganca Radek , Newbold Charles James
Published: February 2019

Although the potential of plants extracts to improve feed efficiency and animal productivity and decrease methane emissions by enteric fermentation has been shown, the information available is often contradictory which has been attributed to differences in the complex mixture of bioactive compounds and their interactions. Understanding the degree to which structural features in a compound may affect the biological activity of an extract is essential. We hypothesised that relative small variations in the structure of a compound can have a significant influence on the ability of the derivatives to alter fermentation in the rumen. Nine compounds were synthetized from the natural alkaloid haemanthamine and tested in vitro for their effects on rumen protozoa and fermentation parameters. Our results showed that simple esterifications of haemanthamine or its derivative dihydrohaemanthamine with acetate, butyrate, pivalate or hexanoate led to compounds that differed in their effects on rumen fermentation.