bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell cycle regulation and novel structural features of thymidine kinase, an essential enzyme in Trypanosoma brucei
Authors: Valente Maria , Timm Jennifer , Castillo‐Acosta Víctor M. , Ruiz‐Pérez Luis M. , Balzarini Tom , Nettleship Joanne E. , Bird Louise E. , Rada Heather , Wilson Keith S. , González‐Pacanowska Dolores 
Published: July 2016

SummaryThymidine kinase (TK) is a key enzyme in the pyrimidine salvage pathway which catalyzes the transfer of the γ‐phosphate of ATP to 2′‐deoxythymidine (dThd) forming thymidine monophosphate (dTMP). Unlike other type II TKs, the Trypanosoma brucei enzyme (TbTK) is a tandem protein with two TK homolog domains of which only the C‐terminal one is active. In this study, we establish that TbTK is essential for parasite viability and cell cycle progression, independently of extracellular pyrimidine concentrations. We show that expression of TbTK is cell cycle regulated and that depletion of TbTK leads to strongly diminished dTTP pools and DNA damage indicating intracellular dThd to be an essential intermediate metabolite for the synthesis of thymine‐derived nucleotides. In addition, we report the X‐ray structure of the catalytically active domain of TbTK in complex with dThd and dTMP at resolutions up to 2.2 Å. In spite of the high conservation of the active site residues, the structures reveal a widened active site cavity near the nucleobase moiety compared to the human enzyme. Our findings strongly support TbTK as a crucial enzyme in dTTP homeostasis and identify structural differences within the active site that could be exploited in the process of rational drug design.
A study with pharyngeal and esophageal 24‐hour pH–impedance monitoring in patients with laryngopharyngeal symptoms refractory to proton pump inhibitors
Authors: Dulery C. , Lechot A. , Roman S. , Bastier P.‐L. , Stoll D. , de Gabory L. , Zerbib F. 
Published: July 2016

AbstractBackgroundThe role of gastroesophageal reflux in chronic laryngeal symptoms is difficult to establish. The aim of this study was to characterize pharyngeal and esophageal pH–impedance reflux patterns in a group of patients with suspected laryngopharyngeal reflux and to determine predictive factors of response to proton pump inhibitors.MethodsPatients with chronic pharyngolaryngeal symptoms were evaluated with a symptom score questionnaire, laryngoscopy, and 24‐hour pharyngeal and esophageal pH–impedance monitoring at baseline and after 8‐week treatment with esomeprazole 40 mg b.i.d. Response to treatment was defined by a diminution of more than 50% of the score for the primary symptom. Reflux patterns and baseline impedance values were compared to those obtained in 46 healthy subjects.Key ResultsTwenty‐four patients were included (17 women, median age 54 years), all previously refractory to antisecretory therapy. Symptom scores were 46 (32–62) and 40 (27–76) off and on therapy, respectively (P=.1). There was no significant difference between patients and controls for pH–impedance reflux parameters and baseline values off and on therapy in distal and proximal esophagus and in the pharynx. Median numbers of pharyngeal reflux were 0 and 0 off and on therapy, respectively. Only two patients were responders to treatment, both with excessive distal reflux but no pharyngeal reflux. Only one patient had abnormal pharyngeal reflux but did not respond to proton pump inhibitors.ConclusionsPatients with suspected laryngopharyngeal reflux refractory to therapy do not exhibit abnormal pharyngeal or esophageal pH–impedance reflux. In these patients, laryngopharyngeal reflux is unlikely.
Molecular genetics and evolution of disease resistance in cereals
Authors: Krattinger Simon G. , Keller Beat 
Published: July 2016

SummaryCereal crops produce a large part of the globally consumed food and feed. Because of the constant presence of devastating pathogens, the molecular characterization of disease resistance is a major research area and highly relevant for breeding. There has been recent and accelerating progress in the understanding of three distinct resistance mechanisms in cereals: resistance conferred by plasma membrane‐localized receptor proteins; race‐specific resistance conferred by intracellular immune receptors; and quantitative disease resistance. Intracellular immune receptors provide a particularly rich source for evolutionary studies, and have, for example, resulted in the recent discovery of a novel detection mechanism based on integrated decoy domains. Evolutionary studies have also revealed the origins of active resistance genes in both wild progenitors of today's cereals as well as in cultivated forms. In addition, independent evolution of orthologous genes in related cereals has resulted in resistance to different pathogen species. Quantitative resistance genes have been best characterized in wheat. The quantitative resistance genes identified so far in wheat encode transporter proteins or unusual kinase proteins. The recent discoveries in these three different resistance mechanisms have contributed to the basic molecular understanding of cereal immunity against pathogens and have suggested novel applications for resistance breeding.

Contents

Summary
320

I.
Introduction
320

II.
Immunity in plants
321

III.
Receptors in the plant plasma membrane – the importance of monitoring the extracellular space
321

IV.
Inside the cell – the role of intracellular immune receptors in cereals
322

V.
NLR evolution in Triticeae
324

VI.
Quantitative disease resistance – why plasma membrane‐localized receptors and NLRs are not sufficient to explain disease resistance in cereals
328

VII.
Conclusions: evolutionary studies of cereal resistance genes contribute to both basic research and breeding
329

Acknowledgements
330

References
330
Resting blood pressure differentially predicts time course in a tonic pain experiment
Authors: Horing Bjoern , McCubbin James A. , Moore Dewayne , Muth Eric R. 
Published: July 2016

AbstractResting blood pressure (BP) shows a negative relationship with pain sensitivity (BP‐related hypoalgesia). In chronic pain conditions, this relationship is inverted. The precise mechanisms responsible for the inversion are unknown. Using a tonic pain protocol, we report findings closely resembling this inversion in healthy participants. Resting BP and state measures of anxiety and mood were assessed from 33 participants (21 female). Participants then immersed their dominant hand in painfully hot water (47 °C) for five trials of 1‐min duration, with 30‐s intertrial intervals. Throughout the trials, participants continually registered their pain. After a 35‐min intermission, the trial sequence was repeated. A disassociation of the negative relationship of resting systolic BP (as per Trial 1) was found using hierarchical linear modeling (p < .001, R2 = .07). The disassociation unfolds over each consecutive trial, with an increasingly positive relationship. In Sequence 2, the initially negative relationship is almost completely absent. Furthermore, the association of BP and pain was found to be moderated by anxiety, such that only persons with low anxiety exhibited BP hypoalgesia. Our findings expand the existing literature by incorporating anxiety as a moderator of BP hypoalgesia. Furthermore, the protocol emulates the changing relationship between BP and pain observed in chronic pain patients. The protocol has potential as a model for chronic pain; however, future research should determine if similar physiological systems are involved. The finding holds potential diagnostic or prognostic relevance for certain clinical pain conditions, especially those involving dysfunction of the descending modulation of pain.
A Comparison of Intergenerational Mobility Curves in Germany, Norway, Sweden, and the US
Authors: Bratberg Espen , Davis Jonathan , Mazumder Bhashkar , Nybom Martin , Schnitzlein Daniel D. , Vaage Kjell 
Published: July 2016

AbstractWe examine intergenerational mobility differences between Germany, Norway, Sweden, and the US. Using ranks, we find that the US is substantially less intergenerationally mobile than the three European countries and that the most mobile region of the US is less mobile than the least mobile regions of Norway and Sweden. Using a linear estimator of income share mobility, we find that the four countries have very similar rates of intergenerational mobility. However, when we use non‐parametric versions of rank and income share mobility, we find that the US tends to experience lower upward mobility at the bottom of the income distribution than Norway and Sweden.
Actual and predicted prevalence of alcohol consumption during pregnancy in the WHO African Region
Authors: Popova Svetlana , Lange Shannon , Probst Charlotte , Shield Kevin , Kraicer‐Melamed Hannah , Ferreira‐Borges Carina , Rehm Jürgen 
Published: July 2016

AbstractObjectiveTo estimate the prevalence of alcohol consumption and binge drinking during pregnancy among the general population in the World Health Organization (WHO) African Region, by country.MethodsFirst, a comprehensive systematic literature search was performed to identify all published and unpublished studies. Then, several meta‐analyses, assuming a random‐effects model, were conducted to estimate the prevalence of alcohol consumption and binge drinking during pregnancy among the general population for countries in the WHO African Region with two or more studies available. Lastly, for countries with less than two studies or no known data predictions were obtained using regression modelling.ResultsThe estimated prevalence of alcohol consumption during pregnancy among the general population ranged from 2.2% (95% confidence interval [CI]: 1.6–2.8%; Equatorial Guinea) to 12.6% (95% CI: 9.9–15.4%; Cameroon) in Central Africa, 3.4% (95% CI: 2.6–4.3%; Seychelles) to 20.5% (95% CI: 16.4–24.7%; Uganda) in Eastern Africa, 5.7% (95% CI: 4.4–7.1%; Botswana) to 14.2% (95% CI: 11.1–17.3%; Namibia) in Southern Africa, 6.6% (95% CI: 5.0–8.3%; Mauritania) to 14.8% (95% CI: 11.6–17.9%; Sierra Leone) in Western Africa, and 4.3% (95% CI: 3.2–5.3%; Algeria) in Northern Africa.ConclusionsThe high prevalence of alcohol consumption and binge drinking during pregnancy in some African countries calls for educational campaigns, screening and targeted interventions for women of childbearing age.
Retrograde signalling caused by heritable mitochondrial dysfunction is partially mediated by ANAC017 and improves plant performance
Authors: Van Aken Olivier , Ford Ethan , Lister Ryan , Huang Shaobai , Millar A.Harvey 
Published: July 2016

SummaryMitochondria are crucial for plant viability and are able to communicate information on their functional status to the cellular nucleus via retrograde signalling, thereby affecting gene expression. It is currently unclear if retrograde signalling in response to constitutive mitochondrial biogenesis defects is mediated by the same pathways as those triggered during acute mitochondrial dysfunction. Furthermore, it is unknown if retrograde signalling can effectively improve plant performance when mitochondrial function is constitutively impaired. Here we show that retrograde signalling in mutants defective in mitochondrial proteins RNA polymerase rpotmp or prohibitin atphb3 can be suppressed by knocking out the transcription factor ANAC017. Genome‐wide RNA‐seq expression analysis revealed that ANAC017 is almost solely responsible for the most dramatic transcriptional changes common to rpotmp and atphb3 mutants, regulating classical marker genes such as alternative oxidase 1a (AOX1a) and also previously‐uncharacterised DUF295 genes that appear to be new retrograde markers. In contrast, ANAC017 does not regulate intra‐mitochondrial gene expression or transcriptional changes unique to either rpotmp or atphb3 genotype, suggesting the existence of currently unknown signalling cascades. The data show that ANAC017 function extends beyond common retrograde transcriptional responses and affects downstream protein abundance and enzyme activity of alternative oxidase, as well as steady‐state energy metabolism in atphb3 plants. Furthermore, detailed growth analysis revealed that ANAC017‐dependent retrograde signalling provides benefits for growth and productivity in plants with mitochondrial defects. In conclusion, ANAC017 plays a key role in both biogenic and operational mitochondrial retrograde signalling, and improves plant performance when mitochondrial function is constitutively impaired.
Current Account ‘Core–Periphery Dualism’ in the EMU
Authors: De Santis Roberta , Cesaroni Tatiana 
Published: July 2016

AbstractCurrent account (CA) dispersion within European Union (EU) Member States has been increasing progressively since the 1990s. Interestingly, the persistent deficits in many peripheral countries have not been accompanied by a significant growth process able to stimulate a log run rebalancing as neoclassical theory predicts. To shed light on the issue, this paper investigates the determinants of Eurozone CA imbalances, focusing on the role played by financial integration. The analysis considers two samples of 22 OECD and 15 EU countries, three time horizons corresponding to various steps in European integration, different control variables and several panel econometric methods. The results suggest that within the EU group of countries financial integration contributed to explain the CA deterioration in the peripheral countries especially in the post‐EMU period creating an asymmetric behaviour within the EMU. From a financial stability perspective, this ‘divergence’ could hinder the effectiveness of monetary policy. By reducing the apparent benefits of participating in the monetary union, it also raises the risk of a break‐up.
Non-Abelian monopoles as the origin of dark matter
Authors: Falomir H. , Gamboa J. , Méndez F. 
Published: July 2016

We suggest that dark matter may be partially constituted by a dilute ’t Hooft–Polyakov monopoles gas. We reach this conclusion by using the Georgi–Glashow model coupled to a dual kinetic mixing term [Formula: see text] where [Formula: see text] is the electromagnetic field and [Formula: see text] the ’t Hooft tensor. We show that these monopoles carry both (Maxwell) electric and (Georgi–Glashow) magnetic charges and the electric charge quantization condition is modified in terms of a dimensionless real parameter. This parameter could be determined from milli-charged particle experiments.
La prigione e la libertà: due testimonianze del dialogo di Fortini con i classici
Authors: Cataldi Pietro 
Published: July 2016

Análise de dois pequenos voluntes de escritos críticos de Franco Fortini: Dialoghi col Tasso (1999) e Le rose dell'abisso (1991), cinco conversas radiofônicas sobre Tasso, Dante, Leopardi, Manzoni e Pascoli.
11-Ketotestosterone Is a Major Androgen Produced in Human Gonads
Authors: Imamichi Yoshitaka , Yuhki Koh-ichi , Orisaka Makoto , Kitano Takeshi , Mukai Kuniaki , Ushikubi Fumitaka , Taniguchi Takanobu , Umezawa Akihiro , Miyamoto Kaoru , Yazawa Takashi 
Published: July 2016

Context:
11-ketotestosterone (11-KT) is a novel class of active androgen. However, the detail of its synthesis remains unknown for humans.

Objective:
The objective of this study was to clarify the production and properties of 11-KT in human.

Design, Participants, and Methods:
Expression of cytochrome P450 and 11β-hydroxysteroid dehydrogenase types 1 and 2 (key enzymes involved in the synthesis of 11-KT) were investigated in human gonads. The production of 11-KT was investigated in Leydig cells. Plasma concentrations of testosterone and 11-KT were measured in 10 women and 10 men of reproductive age. Investigation of its properties was performed using breast cancer-derived MCF-7 cells.

Results:
Cytochrome P450 and 11β-hydroxysteroid dehydrogenase types 1 and 2 were detected in Leydig cells and theca cells. Leydig cells produced 11-KT, and relatively high levels of plasma 11-KT were measured in both men and women. There was no sexual dimorphism in the plasma levels of 11-KT, even though testosterone levels were more than 20 times higher in men than in women. It is noteworthy that the levels of testosterone and 11-KT were similar in women. In a luciferase reporter system, 11-KT activated human androgen receptor-mediated transactivation. Conversely, 11-KT did not activate estrogen receptor-mediated transactivation in aromatase-expressed MCF-7 cells, whereas testosterone did following conversion to estrogen. 11-KT did not affect the estrogen/estrogen receptor -mediated cell proliferation of MCF-7 cells. Furthermore, it significantly inhibited cell proliferation when androgen receptor was transfected into MCF-7 cells.

Conclusions:
The current study indicates that 11-KT is produced in the gonads and represents a major androgen in human. It can potentially serve as a nonaromatizable androgen.
O Uso das Ferramentas na Educação a Distância e o Papel do Tutor
Authors: Dias Auderlânia De Oliveira , Silva Adriana Maria Simião da 
Published: July 2016

RESUMO: Este artigo busca apresentar a importância do papel do professor-tutor na modalidade à distância e as ferramentas que a acompanha, considerando sua experiência vivida no decorrer de sua vida acadêmica. Através do surgimento das novas tecnologias a internet tornou-se um meio propício para a difusão do conhecimento, aumentando a oferta de cursos superiores à distância, nesse contexto o tutor é responsável por manter uma comunicação ativa com seus alunos através das ferramentas, por isso propomos neste artigo reflexões que abordem a importância do professor-tutor nessa modalidade, destacando suas principais características e funções e as ferramentas utilizadas no ensino à distância. A metodologia utilizada foi a pesquisa bibliográfica, e teve como objetivo descrever e analisar o sistema de tutoria na Educação a Distância bem como suas ferramentas , destacando o importante trabalho do professor-tutor, averiguando suas características e suas qualidades .Concluiu- se também que com esse estudo, contribuiu para repensar a função dos tutores presenciais e a distância atuantes na modalidade de ensino à distância ,utilizando-se das ferramentas tecnológicas , tendo em vista que, acreditamos ser de fundamental importância a realização de formação inicial e continuada com esses profissionais, pois são eles que mantêm contato direto e diário com os alunos.
Educação Ambiental: Um diálogo entre a legislação e a prática dos professores de escolas públicas de Araripina – PE, 2013-2014
Authors: Nascimento Maria Cristina Delmondes , Rolon Júlio César Cardozo 
Published: July 2016

A “Educação Ambiental: Um diálogo entre a legislação e a prática dos professores de escolas públicas de Araripina - Pernambuco, 2013-2014” trata-se de um trabalho investigativo, onde almeja: Discutir como acontece o diálogo entre a legislação e a prática dos professores de duas escolas públicas do município da Araripina – Pernambuco no período de 2013 e 2014. A pesquisa apresenta uma abordagem de investigação quantitativa. O universo de pesquisa foram as escolas públicas Dionísio Bom de Oliveira e Moisés Bom de Oliveira, tendo como os sujeitos da pesquisa um universo de 45 docentes. Para alcançar os objetivos propostos os mesmos foram entrevistados segundo um roteiro estruturado baseado em um questionário, as respostas foram submetidas à analise temática de conteúdo. A pesquisa comprovou que o diálogo entre teoria e prática nas escolas investigadas necessita de maior efetividade para minimizar as dificuldades para implementação e estímulo a atividades e projetos de Educação Ambiental, que é trabalhada nos temas transversais, sendo ela essencial, principalmente quando é voltada para a formação de valores e que se trata de um processo de educação e reflexão permanente na construção de sujeitos cidadãos.
Enfoque fenomenológico de la crítica arquitectónica
Authors: Navarrete Dra. Arq. Sandra 
Published: July 2016

El objetivo central de este trabajo fue definir un método crítico de análisis de la arquitectura que se centre en la experiencia sensible como herramienta de estudio de los aspectos estéticos. Se propone con una validación empírica que permita su generalización. Se realizó un recorte epistemológico situándose en el paradigma posmoderno de la estética. Para la comprensión de los factores que modifican la arquitectura regional, se tomó como objeto de análisis la experiencia espacial de las bodegas de Mendoza. Se sostiene como hipótesis principal que la interpretación crítica de la arquitectura a través de la fenomenología permite un mayor grado de sensibilidad en la concepción de espacios y por lo tanto el aprendizaje de un método de proyecto con aspectos más vinculados al hombre. A partir del análisis realizado de tres bodegas locales con estudiantes de cuarto año de la carrera de arquitectura de la Universidad Nacional de Cuyo, se observó que las vivencias espaciales tienen un alto nivel de pregnancia. Por ello, es posible afirmar que la experiencia sensorial es un aspecto relevante en la formación de una postura conceptual de interés para todas las instancias del proyecto arquitectónico.
Palabras clave
Crítica; Fenomenología; Experiencia sensible; Bodegas
Bioinspired engineering polymers by voxel-based 3D-printing
Authors: Swetly Theresa , Stampfl Jürgen , Kempf Gero , Hucke Rainer-Michael , Willing Marcus , Warkentin Marina 
Published: July 2016

AbstractAdditive manufacturing (AM) has become an important tool in the product development process as it offers the possibility to produce parts of good geometrical quality within a short period of time, allowing geometrical validations and the visualisation of ideas. Yet the application of AM is often limited due to the poor mechanical properties of AM parts. In the automotive sector for example, there is a high demand for tough AM parts which have an impact strength comparable to industrially moulded thermoplasts. This paper explores the possibility to increase the impact strength of AM parts by combining a stiff, hard and brittle component (VeroWhite Plus in this instance) with a soft, elastomer-like component (TangoBlack Plus) and arranging these on a micro-scale level in form of alternating, chess-pattern voxels. While one material was responsible for maintaining a sufficient stiffness and strength of the resulting composite structure, the other material acted as an obstacle for crack propagation. Varying the edge length of the voxels, it was possible to investigate the influence of the microscopic voxel geometry on the part’s macroscopic impact strength. It was shown that the Charpy impact strength could be raised by a factor of eight (from 10.9 kJ/m