bluuebunny/crossref_metadata_2025 huggingface dataset:
Resilience to Weather-Related Disasters of a CBFM Community in Ligao, Albay, Philippines
Authors: Grefalda Liezl B. , Pulhin Juan M. , Santos Elsa P.
Published: December 2017

This study assessed the resilience of a Community-Based Forest Management (CBFM) community in Ligao, Albay, Philippines to weather-related disasters. Resiliency was measured using 38 indicators comprising human, social, natural, financial, and physical capitals. The study used household survey administered to 180 respondents, complemented by focus group discussions (FGD), key informant interviews (KII), and secondary data gathering. Index of five capital assets was calculated using the equation for data normalization by a scale of 0 to 1. The overall resiliency index was estimated by getting the weighted average of all the capital assets. Pearson Correlation, Chi-square and Spearman Correlation were used to analyze the relationship of age, gender, and household size to the overall resiliency of the community. The CBFM community is less resilient with an index of 0.382. This was attributed to a lesser access to social and natural capitals with indices of 0.233 and 0.244, respectively. However, the CBFM program remains a promising strategy in improving the adaptive capacity of upland communities by contributing to the enhancement of their social and natural assets. Results revealed that there is a positive correlation between household size and resiliency while age and gender were not correlated. To build resiliency, it is recommended to increase community capacity through education and skills development, ensure access to services, provide technical and financial support from the government and promote collaboration among various stakeholders.
Integrative description of two new species of Malagasy chirping giant pill-millipedes, genus Sphaeromimus (Diplopoda: Sphaerotheriida: Arthrosphaeridae)
Authors: Moritz Leif , Wesener Thomas
Published: December 2017

The species-rich giant pill-millipedes (Sphaerotheriida) often represent a microendemic component of Madagascar’s mega-invertebrate fauna. Of the chirping genus Sphaeromimus de Saussure & Zehntner, 1902, ten species have been described. Here, we describe two new species of Sphaeromimus integratively, combining light microscopy, scanning electron microscopy, DNA barcoding and micro-CT technology for the first time in a taxonomic description of a giant pill-millipede. S. kalambatritra sp. nov. and S. midongy sp. nov. are the first giant pill-millipedes collected and described from the mountainous rainforests of Kalambatritra and Midongy. Both species show island gigantism compared to their congeners. Our analysis of the mitochondrial COI gene shows that the two species are related to one another with a moderate genetic distance (9.4%), while they are more closely related to an undetermined specimen from the forest of Vevembe (6.3% and 8.4%). They stand in a basal position with S. ivohibe Wesener, 2014 and S. musicus (de Saussure & Zehntner, 1897). The four aforementioned species share a high number of stridulation ribs on the male harp. Our micro-CT analysis provides a look into the head of S. kalambatritra sp. nov. and shows that non-destructive CT methods are a useful tool for studying the inner morphology of giant pill-millipedes.
Univers borgià. Aproximacions històriques, culturals i artístiques als Borja
Authors: Mascarell Purificació
Published: December 2017

Presentació del monogràfic "Univers borgià. Aproximacions històriques, culturals i artístiques als Borja"
Non tamen indignum Borgaei dicere laudes/ Caesaris… (T. Strozzi, Serm. 1, 120-1): L’éloge épique de César Borgia dans l’œuvre d’Ercole Strozzi (Ferrare 1474 ?-1508): Venatio (1498 TPQ- 1505 TAQ), Borgeti canis epicedium, Caesaris Borgiae ducis epicedium..
Authors: Charlet-Mesdjian Béatrice , Voisin Dominique
Published: December 2017

Résumé: La poésie hexamétrique d’E. Strozzi, poète néolatin fort prisé pour sa maîtrise de la versification et son innutrition achevée des sources latines, offre deux apologies de César Borgia. L’une, brève (d’une soixantaine de vers), incluse dans un epyllion cynégétique de plus de 900 vers, campe le Valentinois de son vivant en chasseur et conquérant magnanime. L’autre prend la forme d’un long épicède (492 v.). Certes E. Strozzi applique dans ce poème funèbre épidictique les conventions du genre (lamentations, éloge du défunt, exhortation et consolation à la dédicataire, Lucrèce Borgia, duchesse de Ferrare), toutefois le choix de l’hexamètre et le recours systématique aux procédés et aux sources épiques servent à masquer les zones d’ombre du personnage contesté de César Borgia et détourne le chant funèbre en prophétie consolatoire à l’adresse de la dédicataire.   Mots clés: César Borgia, éloge, épopée, guerres d’Italie, humanisme Abstract: The hexametric poetry of E. Strozzi, admired Neo-latin poet for his mastery of versification and his perfect Latin innutritio contains two C. Borgia’s praises. The first one, rather short (about sixty lines only) and included in a cynegetical epyllion (more than 900 lines), depicts the ‘Valentinois’ still alive as a hunter and a magnanimous conqueror ; the other one takes the form of a long epicedion (492 lines). Of course E. Strozzi applies in this funeral epideictic poem the generic conventions (the lamentations, the praise of the deceased, the exhortation and the consolation to the dedicatee, Lucrezia Borgia, Duchess of Ferrara). However, the metrical choice of hexameter and the systematic use of epical sources and proceedings erase the obscure sides of the controversial Caesar Borgia and transform the funeral lamentation into a consolatory prediction at the address of the dedicatee. Keywords: Caesar Borgia, praise, epic, wars of Italy, humanism
Ressenya a Lola Badia, Lluís Cifuentes, Sadurní Martí, Josep Pujol (eds.), Els manuscrits, el saber i les lletres a la Corona d’Aragó, 1250-1500, Barcelona, Publicacions de l’Abadia de Montserrat, 2016.
Authors: Cabré Lluís
Published: December 2017

Ressenya a Lola Badia, Lluís Cifuentes, Sadurní Martí, Josep Pujol (eds.), Els manuscrits, el saber i les lletres a la Corona d’Aragó, 1250-1500, Barcelona, Publicacions de l’Abadia de Montserrat, 2016. 267 pp. ISBN 978-84-9883-861-9 Review to Lola Badia, Lluís Cifuentes, Sadurní Martí, Josep Pujol (eds.), Els manuscrits, el saber i les lletres a la Corona d’Aragó, 1250-1500, Barcelona, Publicacions de l’Abadia de Montserrat, 2016. 267 pp. ISBN 978-84-9883-861-9
Ressenya a Henry Ettinghausen, How the Press Began. The Pre-Periodical Printed News in Early Modern Europe, A Coruña, SIELAE – Facultad de Filología, Universidade da Coruña, 2015,
Authors: Expósito i Amagat Ricard
Published: December 2017

Ressenya a Henry Ettinghausen, How the Press Began. The Pre-Periodical Printed News in Early Modern Europe, A Coruña, SIELAE – Facultad de Filología, Universidade da Coruña, 2015, 302 pp., 80 il·ls., ISBN: 978-84-608-3423-6 Review to  Henry Ettinghausen, How the Press Began. The Pre-Periodical Printed News in Early Modern Europe, A Coruña, SIELAE – Facultad de Filología, Universidade da Coruña, 2015, 302 pp., 80 il·ls., ISBN: 978-84-608-3423-6
La visita del papa Benet XIII a València de 1414-1415: una aproximació a la seua memòria en la tradició historiogràfica valenciana
Authors: Server Server Blai Josep
Published: December 2017

L’article analitza els testimonis de la visita de Benet XIII, Pero Martínez de Luna, a la ciutat de València entre desembre de 1414 i juliol de 1415 conservats en la tradició historiogràfica valenciana. En concret, s’hi examinen les obres valencianes de caràcter memorialístic (cròniques i dietaris, principalment) que, des del segle XV i fins a l’actualitat, han parat atenció a l’esdeveniment, per concloure que la memòria del mateix es conservà sobretot en els cercles del poder eclesiàstic –particularment entorn de la Seu– i municipal de la ciutat. Més enllà d’aquests àmbits, la visita papal fou progressivament oblidada, a pesar de l’impacte notable que degué tindre sobre aquells que la visqueren directament o en tingueren notícia indirectament a l’inici del segle XV.
Ressenya a Mercedes Gallent Marco, Orígenes del sistema sanitario valenciano. Documentos fundacionales del Hospital General de Valencia, València, Institució Alfons el Magnànim-Centre Valencià d’Estudis i Investigació. Diputació de València, 2016.
Authors: Server Server Blai Josep
Published: December 2017

Ressenya a Mercedes Gallent Marco, Orígenes del sistema sanitario valenciano. Documentos fundacionales del Hospital General de Valencia, València, Institució Alfons el Magnànim, 2016, 259 pp. ISBN 978-84-7822-6851-6 Review to Mercedes Gallent Marco, Orígenes del sistema sanitario valenciano. Documentos fundacionales del Hospital General de Valencia, València, Institució Alfons el Magnànim, 2016, 259 pp. ISBN 978-84-7822-6851-6
«Harpespill, fantasiskalaer og syngende fingre» - om barnehagebarns møter med tre musikkrelaterte apper
Authors: Engesnes Nina , Danbolt Ingrid A. , Hagen Liv Anna
Published: December 2017

Artikkelen tar for seg barnehagebarns møter med tre musikkrelaterte applikasjoner på nettbrett: Air Harp, Bloom og Singing Fingers. Seks grupper med 4-6 barn i alderen 5-6 år har deltatt i studien, og teksten bygger på observasjoner av barnas møter med appene. Forfatternes hensikt er å bidra med kunnskap om hva musikkrelaterte apper kan tilby barnehagebarn av musikalske oppdagelser og skapende utforskning. Funnene tyder på at det ligger muligheter i appene som inspirerer til musikalsk utforsking og lek, der barnas musiske væremåter får handlingsrom. Sentrale begreper i studien er affordanse, musikkens grunnelementer og barns musiske uttrykksmåter.The article is about children in early childhood education exploring three applications with musical content on tablets: Air Harp, Bloom and Singing Fingers. Six groups of 4-6 children aged 5-6 years participated in the study, and the text is based on observations of the children and how they met challenges and explored the features of the tablet and apps. The authors intend to develop knowledge about these apps and their possibilities to offer musical exploration for children in early childhood education. Findings suggest that there is potential in the apps that inspires children to creative musical exploration and play. Central concepts in the study are affordance, musical parameters and children's musical expressions.
Ankle sprain as a work-related accident: status of proprioception after 2 weeks
Authors: González-Iñigo Salvador , Munuera-Martínez Pedro V. , Lafuente-Sotillos Guillermo , Castillo-López José M. , Ramos-Ortega Javier , Domínguez-Maldonado Gabriel
Published: December 2017

Purpose

This study aims at verifying whether proprioception is abnormal or not, two weeks after a grade 1 and 2 ankle sprain in the scope of work-related accident.

Methods

A descriptive, observation and transversal study was designed to compare speed, movement and oscilation of centre of pressure in employees of companies signed up to a mutual company. Participants’ healthy feet comprised the control group, and feet that had undergone an ankle sprain due to a work-related accident comprised the cases group. The following stability tests were undertaken to both the healthy and injuried feet using a force plate: Monopodal Romberg test with eyes open, Monopodal Romberg test with eyes open on a 30 mm thick foam rubber, Monopodal Romberg test with eyes closed, and Romberg test as monopodal support with eyes closed on a 30 mm thick foam rubber. A multiple logistic regression analysis was performed. From the results of this regression model the COR curve test was performed.

Results

71.7% accuracy in the predictions was attained. The equation was as follows:Condition (injured or healthy)=0.052⋅%RGC AP Movement − 0.81⋅MREO AP Movement. The variable MREO antero-posterior movement was used in the COR curve methodology. The area under the curve was greater than 0.65 and at a 95% confidence interval the 0.75 value was included, which in our case was the injured subject condition. Values for sensitivity, specificity, positive predictive value and negative predictive value were 0.667, 0.633, 64.5%, and 65.5%, respectively.

Conclusion

The participants in this study showed a diminished capacity for postural control in an ankle two weeks after an ankle sprain.
LOS LÍMITES AL LEGISLADOR EN LA REGULACIÓN DE LOS DERECHOS: SENTENCIA ROL Nº3729-17 DEL TRIBUNAL CONSTITUCIONAL DE CHILE RECAÍDA EN EL PROYECTO DE LEY QUE REGULA LA DESPENALIZACIÓN DE LA INTERRUPCIÓN DEL EMBARAZO EN TRES CAUSALES
Authors:   Pontificia Universidad Católica de Chile, Ovalle Valdés Alejandra
Published: December 2017

La sentencia del Tribunal Constitucional de Chile recaí­da en el proyecto de ley que despenaliza el delito de aborto en tres causales, contiene un radical giro jurisprudencial en materia del reconocimiento de los derechos esenciales inherentes a la naturaleza humana como lí­mites al poder soberano y, en particular, a la actividad legislativa. Lo razonado por el Tribunal Constitucional en este ámbito no sólo incide en el contenido y alcance del derecho a la vida, sino que impacta a todo el sistema de derechos y a la comprensión de la relación entre la persona y el Estado. Sus consecuencias quedan de manifiesto en el voto disidente concerniente a la regulación de la objeción de conciencia en el proyecto de ley impugnado.
Kinematic Evolution of the Southern North Atlantic: Implications for the Formation of Hyperextended Rift Systems
Authors: Nirrengarten M. , Manatschal G. , Tugend J. , Kusznir N. , Sauter D.
Published: December 2017

We focus on the southern North Atlantic rifted margins to investigate the partitioning and propagation of deformation in hyperextended rift systems using plate kinematic modeling. The kinematic evolution of this area is well determined by oceanic magnetic anomalies after the Cretaceous normal polarity superchron. However, the rift and early seafloor spreading evolution (200–83 Ma) remains highly disputed due to contentious interpretations of the J magnetic anomaly on the Iberia‐Newfoundland conjugate margins. Recent studies highlight that the J anomaly is probably polygenic, related to polyphased magmatic events, and therefore does not correspond to an isochron. We present a new palinspastic restoration without using the J magnetic anomaly as the chron M0. We combine 3‐D gravity inversion results with local structural, stratigraphic, and geochronological constraints on the rift deformation history. The restoration of the southern North Atlantic itself is not the primary aim of the study but rather is used as a method to investigate the spatiotemporal evolution of hyperextended rift systems. We include continental microblocks that enable the partitioning of the deformation between different rift segments, which is of particular importance for the evolution of the Iberia‐Eurasia plate boundary. Our modeling highlights the following: (1) the segmentation of the Iberia‐Newfoundland rift system during continental crust thinning, (2) the northward V‐shape propagation of mantle exhumation and seafloor spreading, (3) the complex partitioning of deformation along the Iberia‐Eurasia plate boundary, and (4) a three‐plate propagation model which implies transtension.
The influence of Shc proteins and high‐fat diet on energy metabolism of mice
Authors: Baldassini W.A. , Ramsey J.J. , Hagopian K. , Lanna D.P.D.
Published: December 2017

The purpose of this study was to determine if Shc proteins influence the metabolic response to acute (7 days) feeding of a high‐fat diet (HFD). To this end, whole animal energy expenditure (EE) and substrate oxidation were measured in the Shc knockout (ShcKO) and wild‐type (WT) mice fed a control or HFD. The activities of enzymes of glycolysis, the citric acid cycle, electron transport chain (ETC), and β‐oxidation were also investigated in liver and skeletal muscle of ShcKO and WT animals. The study showed that ShcKO increases (P < .05) EE adjusted for either total body weight or lean mass. This change in EE could contribute to decreases in weight gain in ShcKO versus WT mice fed an HFD. Thus, our results indicate that Shc proteins should be considered as potential targets for developing interventions to mitigate weight gain on HFD by stimulating EE. Although decreased levels of Shc proteins influenced the activity of some enzymes in response to high‐fat feeding (eg, increasing the activity of acyl‐CoA dehydrogenase), it did not produce concerted changes in enzymes of glycolysis, citric acid cycle, or the ETC. The physiological significance of observed changes in select enzyme activities remains to be determined.

Significance of the study:

We report higher EE in ShcKO versus WT mice when consuming the HFD. Although decreased levels of Shc proteins influenced the activity of a central enzyme of β‐oxidation in response to high‐fat feeding, it did not produce concerted changes in enzymes of glycolysis, citric acid cycle, or the ETC. Thus, an increase in EE in response to consumption of an HFD may be a mechanism that leads to decreased weight gain previously reported in ShcKO mice with long‐term consumption of an HFD.
Socio‐Economic Interest of Treated Wastewater Reuse in Agricultural Irrigation and Indirect Potable Water Reuse: Clermont‐Ferrand and Cannes Case Studies' Cost–Benefit Analysis
Authors: Declercq Rémi , Loubier Sébastien , Condom Nicolas , Molle Bruno
Published: December 2017

Unlike many structuring projects, treated wastewater reuse projects are rarely subjected to economic analysis. And when they are, the social and environmental benefits and costs are often not accounted for or are not properly quantified. Here we show that the widely used cost–benefit analysis method showing the profitability of a project from the whole of the community's point of view can be adapted to treated wastewater reuse projects. The remaining evaluation difficulties are more due to the system's complexity rather than its methodological limits. Indeed, the operator must be able to understand, formalize and imagine constraints and risks associated with different domains such as urbanism, agriculture, climate, hydrology and trade. Remaining uncertainties over key parameter values can, however, be properly considered through scenarios and/or stochastic approaches. We illustrate the implementation of this methodological approach with two case studies: Clermont‐Ferrand where treated wastewater is reused by a collective irrigation network; and Cannes where surface and groundwater recharge can enable indirect reuse for multiple purposes including indirect potable water production. These two French case studies highlight how economic analysis, dealing with uncertainties, can support decision making. Copyright © 2020 John Wiley & Sons, Ltd.
The magnetic Rayleigh–Taylor instability in solar prominences
Authors: Hillier Andrew
Published: December 2017

The magnetic Rayleigh–Taylor instability is a fundamental instability of many astrophysical systems, and recent observations are consistent with this instability developing in solar prominences. Prominences are cool, dense clouds of plasma that form in the solar corona that display a wide range of dynamics of a multitude of spatial and temporal scales, and two different phenomena that have been discovered to occur in prominences can be understood as resulting from the Rayleigh–Taylor instability. The first is that of plumes that rise through quiescent prominences from low density bubbles that form below them. The second is that of a prominence eruption that fragments as the material falls back to the solar surface. To identify these events as the magnetic Rayleigh–Taylor instability, a wide range of theoretical work, both numerical and analytical has been performed, though alternative explanations do exist. For both of these sets of observations, determining that they are created by the magnetic Rayleigh–Taylor instability has meant that the linear instability conditions and nonlinear dynamics can be used to make estimates of the magnetic field strength. There are strong connections between these phenomena and those in a number of other astro, space and plasma systems, making these observations very important for our understanding of the role of the Rayleigh–Taylor instability in magnetised systems.
Increase in the prevalence of abdominal obesity in Brazilian schoo children (2000-2015)
Authors: Casagrande Daniela , Waib Paulo H. , Sgarbi José A.
Published: December 2017

Introduction:

The prevalence of overweight and obese children and adolescents is a public health concern. Few studies have critically evaluated this problem in a Brazilian population, despite the growth of community-based programs to combat childhood obesity in this country.

Objective:

To study the anthropometrics of Brazilian adolescents over a fifteen-year period.

Methods:

In a cross-sectional analysis, we investigated the anthropometric status of male and female adolescents in Brazil. The anthropometric data and nutritional status of 595 schoolchildren in the year 2000 were compared to 636 schoolchildren in 2015.

Results:

We found a significant increase in the prevalence of overweight or obese adolescents in 2015 compared to 2000 (23.4% vs. 18.3%, p = .027). A sub-analysis stratified by sex showed that this increase only occurred in females. No statistically significant difference was observed in body mass index between the groups. Waist circumference (73.5 cm vs. 77 cm, p < .001) and the prevalence of abdominal obesity (30% vs. 47.9%, p < .001) were significantly greater in 2015, regardless of sex.

Conclusion:

Overweight or obese children, as well as abdominal obesity were more prevalent in 2015 than in preceding decades. This is a worrying trend as abdominal obesity increases the risk for cardiometabolic morbidity and mortality in adult life.
Dispute Settlement Reports 2004:1
Authors: World Trade Organization
Published: December 2017

The Dispute Settlement Reports of the World Trade Organization (WTO) include Panel and Appellate Body reports, as well as arbitration awards, in disputes concerning the rights and obligations of WTO members under the provisions of the Marrakesh Agreement Establishing the World Trade Organization. These are the WTO authorized and paginated reports in English. An essential addition to the library of all practising and academic trade lawyers, and needed by students worldwide taking courses in international economic or trade law. DSR 2004: I reports on sunset review of anti-dumping duties on corrosion-resistant carbon steel flat products from Japan (US), and contains a cumulative index of published disputes.
Dispute Settlement Reports 2005
Authors: World Trade Organization
Published: December 2017

The Dispute Settlement Reports of the World Trade Organization (WTO) include Panel and Appellate Body reports, as well as arbitration awards, in disputes concerning the rights and obligations of WTO members under the provisions of the Marrakesh Agreement Establishing the World Trade Organization. These are the WTO authorized and paginated reports in English. An essential addition to the library of all practising and academic trade lawyers, and needed by students worldwide taking courses in international economic or trade law. DSR 2005:III reports on United States - Subsidies on Upland Cotton.
Dispute Settlement Reports 2005
Authors: World Trade Organization
Published: December 2017

The Dispute Settlement Reports of the World Trade Organization (WTO) include Panel and Appellate Body reports, as well as arbitration awards, in disputes concerning the rights and obligations of WTO members under the provisions of the Marrakesh Agreement Establishing the World Trade Organization. These are the WTO authorized and paginated reports in English. An essential addition to the library of all practising and academic trade lawyers, and needed by students worldwide taking courses in international economic or trade law. DSR 2005:VII reports on Korea - Measures Affecting Trade in Commercial Vessels.
The monounsaturated fatty acid oleate is the major physiological toxic free fatty acid for human beta cells
Authors: Plötz T , Krümmel B , Laporte A , Pingitore A , Persaud SJ , Jörns A , Elsner M , Mehmeti I , Lenzen S
Published: December 2017

Free fatty acids (FFAs) can cause glucose intolerance and diabetes. Lipotoxicity to the pancreatic beta cells is considered to be a major underlying cause for this phenomenon. The aim of this study was to analyse the toxicity profile of FFAs in the human EndoC-βH1 beta-cell line and to compare the results with isolated rat and human islets with special reference to the physiologically most prevalent FFAs palmitic acid (PA) and oleic acid (OA). Toxicity after a 2-day incubation with the different FFAs was analysed by the caspase-3 assay and confirmed by the propidium iodide and annexin V staining tests. The long-chain saturated PA (C16:0) and the monounsaturated OA (C18:1) were both toxic to human EndoC-βH1 beta cells and pseudoislets, as well as to rat islets, and, as confirmed in a pilot experiment, also to human islets. Furthermore, OA provided no protection against the toxicity of PA. Likewise, elaidic acid (EA, the trans isomer of OA; trans-OA) was significantly toxic, in contrast to the non-metabolisable analogues methylated PA (MePA) and methylated OA (MeOA). Fatty acids with a chain length  < C16 were not toxic in EndoC-βH1 beta cells. Caspase-3 was also activated by linoleic acid (LA)(C18:2) but not by γ-linolenic acid (γ-LNA)(C18:3). Overall, only long-chain FFAs with chain lengths  > C14, which generate hydrogen peroxide in the peroxisomal beta-oxidation, were toxic. This conclusion is also supported by the toxicity of the branched-chain FFA pristanic acid, which is exclusively metabolised in the peroxisomal beta-oxidation. The lack of a protective effect of the monounsaturated fatty acid OA has important consequences for a beta-cell protective lipid composition of a diet. A cardioprotective diet with a high OA content does not fulfil this requirement.
“DNA Methylation signatures in panic disorder”
Authors: Iurato Stella , Carrillo-Roa Tania , Arloth Janine , Czamara Darina , Diener-Hölzl Laura , Lange Jennifer , Müller-Myhsok Bertram , Binder Elisabeth B. , Erhardt Angelika
Published: December 2017

Panic disorder (PD) affects about four million Europeans, with women affected twice as likely as men, causing substantial suffering and high economic costs. The etiopathogenesis of PD remains largely unknown, but both genetic and environmental factors contribute to risk. An epigenome-wide association study (EWAS) was conducted to compare medication-free PD patients (n = 89) with healthy controls (n = 76) stratified by gender. Replication was sought in an independent sample (131 cases, 169 controls) and functional analyses were conducted in a third sample (N = 71). DNA methylation was assessed in whole blood using the Infinium HumanMethylation450 BeadChip. One genome-wide association surviving FDR of 5% (cg07308824, P = 1.094 × 10-7, P-adj = 0.046) was identified in female PD patients (N = 49) compared to controls (N = 48). The same locus, located in an enhancer region of the HECA gene, was also hypermethylated in female PD patients in the replication sample (P = 0.035) and the significance of the association improved in the meta-analysis (P-adj = 0.004). Methylation at this CpG site was associated with HECA mRNA expression in another independent female sample (N = 71) both at baseline (P = 0.046) and after induction by dexamethasone (P = 0.029). Of 15 candidates, 5 previously reported as associated with PD or anxiety traits also showed differences in DNA methylation after gene-wise correction and included SGK1, FHIT, ADCYAP1, HTR1A, HTR2A. Our study examines epigenome-wide differences in peripheral blood for PD patients. Our results point to possible sex-specific methylation changes in the HECA gene for PD but overall highlight that this disorder is not associated with extensive changes in DNA methylation in peripheral blood.
A molecular basis for water motion detection by the mechanosensory lateral line of zebrafish
Authors: Chou Shih-Wei , Chen Zongwei , Zhu Shaoyuan , Davis Robin W. , Hu Jiaqi , Liu Li , Fernando Carol A. , Kindig Kayla , Brown William C. , Stepanyan Ruben , McDermott Brian M.
Published: December 2017

Detection of water motion by the lateral line relies on mechanotransduction complexes at stereocilia tips. This sensory system is comprised of neuromasts, patches of hair cells with stereociliary bundles arranged with morphological mirror symmetry that are mechanically responsive to two opposing directions. Here, we find that transmembrane channel-like 2b (Tmc2b) is differentially required for mechanotransduction in the zebrafish lateral line. Despite similarities in neuromast hair cell morphology, three classes of these cells can be distinguished by their Tmc2b reliance. We map mechanosensitivity along the lateral line using imaging and electrophysiology to determine that a hair cell’s Tmc2b dependence is governed by neuromast topological position and hair bundle orientation. Overall, water flow is detected by molecular machinery that can vary between hair cells of different neuromasts. Moreover, hair cells within the same neuromast can break morphologic symmetry of the sensory organ at the stereocilia tips.
Lipid moieties on lipoproteins of commensal and non-commensal staphylococci induce differential immune responses
Authors: Nguyen Minh-Thu , Uebele Julia , Kumari Nimerta , Nakayama Hiroshi , Peter Lena , Ticha Olga , Woischnig Anne-Kathrin , Schmaler Mathias , Khanna Nina , Dohmae Naoshi , Lee Bok Luel , Bekeredjian-Ding Isabelle , Götz Friedrich
Published: December 2017

Lipoproteins (Lpp) of Gram-positive bacteria are major players in alerting our immune system. Here, we show that the TLR2 response induced by commensal species Staphylococcus aureus and Staphylococcus epidermidis is almost ten times lower than that induced by noncommensal Staphylococcus carnosus, and this is at least partially due to their different modifications of the Lpp lipid moieties. The N terminus of the lipid moiety is acylated with a long-chain fatty acid (C17) in S. aureus and S. epidermidis, while it is acylated with a short-chain fatty acid (C2) in S. carnosus. The long-chain N-acylated Lpp, recognized by TLR2–TLR1 receptors, silences innate and adaptive immune responses, while the short-chain N-acetylated Lpp, recognized by TLR2–TLR6 receptors, boosts it.
Spontaneous and specific chemical cross-linking in live cells to capture and identify protein interactions
Authors: Yang Bing , Tang Shibing , Ma Cheng , Li Shang-Tong , Shao Guang-Can , Dang Bobo , DeGrado William F. , Dong Meng-Qiu , Wang Peng George , Ding Sheng , Wang Lei
Published: December 2017

Covalently locking interacting proteins in situ is an attractive strategy for addressing the challenge of identifying weak and transient protein interactions, yet it is demanding to execute chemical reactions in live systems in a biocompatible, specific, and autonomous manner. Harnessing proximity-enabled reactivity of an unnatural amino acid incorporated in the bait toward a target residue of unknown proteins, here we genetically encode chemical cross-linkers (GECX) to cross-link interacting proteins spontaneously and selectively in live cells. Obviating an external trigger for reactivity and affording residue specificity, GECX enables the capture of low-affinity protein binding (affibody with Z protein), elusive enzyme-substrate interaction (ubiquitin-conjugating enzyme UBE2D3 with substrate PCNA), and endogenous proteins interacting with thioredoxin in E. coli cells, allowing for mass spectrometric identification of interacting proteins and crosslinking sites. This live cell chemistry-based approach should be valuable for investigating currently intangible protein interactions in vivo for better understanding of biology in physiological settings.
Phased uplift of the northeastern Tibetan Plateau inferred from a pollen record from Yinchuan Basin, northwestern China
Authors: Li Xinling , Hao Qingzhen , Wei Mingjian , Andreev Andrei A. , Wang Junping , Tian Yanyan , Li Xiaolei , Cai Maotang , Hu Jianmin , Shi Wei
Published: December 2017

The uplift of the Tibetan Plateau (TP) significantly affected both regional and global climates. Although there is evidence that the Tibetan Plateau experienced uplift during the Quaternary, the timing and amplitude are poorly constrained. However, the increased availability of long sedimentary records of vegetation change provides an opportunity to reconstruct the timing of the uplift. Here, we present a well-dated, high-resolution pollen record for the last 2.6 Ma from the Yinchuan Basin, which was incised by the Yellow River with its source in the northeastern Tibetan Plateau. Variations in the Artemisia/Chenopodiaceae (A/C) ratio of the reveal changes in moisture conditions in the Yinchuan Basin during glacial-interglacial cycles, as well as a gradual long-term aridification trend which is consistent with progressive global cooling. However, fluctuations in the percentages of Picea and Abies differ from those of the A/C ratio and we propose that they reflect changes in the vegetation and environment of high elevation areas. The Picea and Abies records reveal two phases of increased representation, at 2.1 and 1.2 Ma, which may indicate phases in the uplift of the northeastern Tibetan Plateau. Thus, they provide independent evidence for the timing of the uplift of the Tibetan Plateau during the Quaternary.
Fabrication of pH-responsive PLGA(UCNPs/DOX) nanocapsules with upconversion luminescence for drug delivery
Authors: Zhao Junwei , Yang Hui , Li Jili , Wang Yujiang , Wang Xin
Published: December 2017

The integration of anticancer drugs and inorganic nanocrystals in polymer nanocapsules is a widely used strategy to improve their functionality, stability and sustained release. However, the complexity in the preparation of functional nanocapsules and their reproducibility still challenge these promising drug carriers in clinical application. Here we introduce a simple one-step self-assembly strategy to prepare multifunctional nanocapsules based on simultaneous poly (DL-lactic-co-glycolic acid) (PLGA) encapsulation of antitumor drug doxorubicin hydrochloride (DOX) and NaYF4:Yb,Er@NaGdF4 upconversion nanoparticles (UCNPs) for cancer cell imaging and drug delivery. The obtained PLGA(UCNPs/DOX) nanocapsules with a small size of ≈150 nm possessed bright upconversion fluorescence and could act as T1-
weighted contrast agents for magnetic resonance imaging (MRI). Moreover, the PLGA(UCNPs/DOX) nanocapsules exhibited pH-responsive drug releasing behavior, causing the loaded DOX easily releasing at cancer cells, and an obvious cytotoxicity via MTT assay. The endocytosis process of PLGA (UCNPs/DOX) nanocapsules is evaluated using optical microscopy and upconversion fluorescence microscopy. These results demonstrated that the developed PLGA nanocapsules could serve as multifunctional drug delivery systems for cancer imaging and therapy.
Generation of therapeutic protein variants with the human serum albumin binding capacity via site-specific fatty acid conjugation
Authors: Cho Jinhwan , Lim Sung In , Yang Byung Seop , Hahn Young S. , Kwon Inchan
Published: December 2017

Extension of the serum half-life is an important issue in developing new therapeutic proteins and expanding applications of existing therapeutic proteins. Conjugation of fatty acid, a natural human serum albumin ligand, to a therapeutic protein/peptide was developed as a technique to extend the serum half-life in vivo by taking advantages of unusually long serum half-life of human serum albumin (HSA). However, for broad applications of fatty acid-conjugation, several issues should be addressed, including a poor solubility of fatty acid and a substantial loss in the therapeutic activity. Therefore, herein we systematically investigate the conditions and components in conjugation of fatty acid to a therapeutic protein resulting in the HSA binding capacity without compromising therapeutic activities. By examining the crystal structure and performing dye conjugation assay, two sites (W160 and D112) of urate oxidase (Uox), a model therapeutic protein, were selected as sites for fatty acid-conjugation. Combination of site-specific incorporation of a clickable p-azido-L-phenylalanine to Uox and strain-promoted azide-alkyne cycloaddition allowed the conjugation of fatty acid (palmitic acid analog) to Uox with the HSA binding capacity and retained enzyme activity. Deoxycholic acid, a strong detergent, greatly enhanced the conjugation yield likely due to the enhanced solubility of palmitic acid analog.
Proteomic investigation of effects of hydroxysafflor yellow A in oxidized low-density lipoprotein-induced endothelial injury
Authors: Ye Feng , Wang Jianhe , Meng Wei , Qian Jingru , Jin Ming
Published: December 2017

Oxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial damage is a key event in early atherosclerosis. Safflower has been used to treat atherosclerotic heart disease in China for many years, but its molecular basis remains unclear. Hydroxysafflor yellow A (HSYA) is the main active ingredient of aqueous safflower extract. We identified the proteins involved in HSYA activity against ox-LDL-induced endothelial injury using isobaric tags for relative and absolute quantification-coupled two-dimensional liquid chromatography–tandem mass spectrometry. HSYA (1, 5, or 25 μM) alleviated ox-LDL-induced endothelial damage in a dose-dependent manner. We quantitated approximately 2700 protein species, of which 77 were differentially expressed following HSYA treatment. Most protein changes were related to structural molecules, metabolic enzymes, and proteins involved in signal transduction. Several differentially expressed proteins were further validated by western blot analysis. We also analysed the role of the mitochondrial membranous voltage-dependent anion-selective channel protein 2 (VDAC2) in HSYA treatment using small interfering RNA. VDAC2 functioned as a downstream anti-apoptosis effector during HSYA treatment of ox-LDL-induced endothelial impairment. These results further our understanding of the mechanisms responsible for the effects of HSYA.
CRTC1 mediates preferential transcription at neuronal activity-regulated CRE/TATA promoters
Authors: Parra-Damas Arnaldo , Rubió-Ferrarons Laura , Shen Jie , Saura Carlos A.
Published: December 2017

Gene expression mediated by the transcription factor cAMP-responsive element-binding protein (CREB) is essential for a wide range of brain processes. The transcriptional coactivartor CREB-regulated transcription coactivator-1 (CRTC1) is required for efficient induction of CREB target genes during neuronal activity. However, the mechanisms regulating induction of specific CREB/CRTC1-dependent genes during neuronal activity remain largely unclear. Here, we investigated the molecular mechanisms regulating activity-dependent gene transcription upon activation of the CREB/CRTC1 signaling pathway in neurons. Depolarization and cAMP signals induce preferential transcription of activity-dependent genes containing promoters with proximal CRE/TATA sequences, such as c-fos, Dusp1, Nr4a1, Nr4a2 and Ptgs2, but not genes with proximal CRE/TATA-less promoters (e.g. Nr4a3, Presenilin-1 and Presenilin-2). Notably, biochemical and chromatin immunoprecipitation analyses reveal constitutive binding of CREB to target gene promoters in the absence of neuronal activity, whereas recruitment of CRTC1 to proximal CRE/TATA promoters depends on neuronal activity. Neuronal activity induces rapid CRTC1 dephosphorylation, nuclear translocation and binding to endogenous CREB. These results indicate that neuronal activity induces a preferential binding of CRTC1 to the transcriptional complex in CRE/TATA-containing promoters to engage activity-dependent transcription in neurons.
Environment spectrum and coherence behaviours in a rare-earth doped crystal for quantum memory
Authors: Gong Bo , Tu Tao , Zhou Zhong-Quan , Zhu Xing-Yu , Li Chuan-Feng , Guo Guang-Can
Published: December 2017

We theoretically investigate the dynamics of environment and coherence behaviours of the central ion in a quantum memory based on a rare-earth doped crystal. The interactions between the central ion and the bath spins suppress the flip-flop rate of the neighbour bath spins and yield a specific environment spectral density S(ω). Under dynamical decoupling pulses, this spectrum provides a general scaling for the coherence envelope and coherence time, which significantly extend over a range on an hour-long time scale. The characterized environment spectrum with ultra-long coherence time can be used to implement various quantum communication and information processing protocols.
Ablation of peri-insult generated granule cells after epilepsy onset halts disease progression
Authors: Hosford Bethany E. , Rowley Shane , Liska John P. , Danzer Steve C.
Published: December 2017

Aberrant integration of newborn hippocampal granule cells is hypothesized to contribute to the development of temporal lobe epilepsy. To test this hypothesis, we used a diphtheria toxin receptor expression system to selectively ablate these cells from the epileptic mouse brain. Epileptogenesis was initiated using the pilocarpine status epilepticus model in male and female mice. Continuous EEG monitoring was begun 2–3 months after pilocarpine treatment. Four weeks into the EEG recording period, at a time when spontaneous seizures were frequent, mice were treated with diphtheria toxin to ablate peri-insult generated newborn granule cells, which were born in the weeks just before and after pilocarpine treatment. EEG monitoring continued for another month after cell ablation. Ablation halted epilepsy progression relative to untreated epileptic mice; the latter showing a significant and dramatic 300% increase in seizure frequency. This increase was prevented in treated mice. Ablation did not, however, cause an immediate reduction in seizures, suggesting that peri-insult generated cells mediate epileptogenesis, but that seizures per se are initiated elsewhere in the circuit. These findings demonstrate that targeted ablation of newborn granule cells can produce a striking improvement in disease course, and that the treatment can be effective when applied months after disease onset.
Structural basis for high specificity of octopine binding in the plant pathogen Agrobacterium tumefaciens
Authors: Vigouroux Armelle , El Sahili Abbas , Lang Julien , Aumont-Nicaise Magali , Dessaux Yves , Faure Denis , Moréra Solange
Published: December 2017

Agrobacterium pathogens of octopine- and nopaline-types force host plants to produce either octopine or nopaline compounds, which they use as nutrients. Two Agrobacterium ABC-transporters and their cognate periplasmic binding proteins (PBPs) OccJ and NocT import octopine and nopaline/octopine, respectively. Here, we show that both octopine transport and degradation confer a selective advantage to octopine-type A. tumefaciens when it colonizes plants. We report the X-ray structures of the unliganded PBP OccJ and its complex with octopine as well as a structural comparison with NocT and the related PBP LAO from Salmonella enterica, which binds amino acids (lysine, arginine and ornithine). We investigated the specificity of OccJ, NocT and LAO using several ligands such as amino acids, octopine, nopaline and octopine analogues. OccJ displays a high selectivity and nanomolar range affinity for octopine. Altogether, the structural and affinity data allowed to define an octopine binding signature in PBPs and to construct a OccJ mutant impaired in octopine binding, a selective octopine-binding NocT and a non-selective octopine-binding LAO by changing one single residue in these PBPs. We proposed the PBP OccJ as a major trait in the ecological specialization of octopine-type Agrobacterium pathogens when they colonize and exploit the plant host.
Bacterial Nanocellulose Loaded with Bromelain: Assessment of Antimicrobial, Antioxidant and Physical-Chemical Properties
Authors: Ataide Janaína Artem , de Carvalho Nathália Mendes , Rebelo Márcia de Araújo , Chaud Marco Vinícius , Grotto Denise , Gerenutti Marli , Rai Mahendra , Mazzola Priscila Gava , Jozala Angela Faustino
Published: December 2017

Bacterial nanocellulose (BNC) has desirable properties for wound healing such as high purity, good shape retention, and high water binding capacity. Bromelain is a protease found in pineapple tissues and has been applied in several fields, it has anti-inflammatory and anticancer properties, promotes cell apoptosis, amongst others. In this work, a BNC based device for the controlled release of bromelain was developed. BNC were submersed in sterilized bromelain solution and incubated at 25 °C under 100 rpm for 24 h. Physical-chemical properties, protein concentration, antioxidant and antimicrobial activities were measured. Results demonstrate that BNC could improve bromelain antimicrobial activity 9 times. Those findings allow concluding that bromelain is a promising molecule to be incorporated into BNC’s. The BNC’s characteristics seem to represent a new promising delivery system of the loaded biomolecule, and protected from external actions.
Thromboembolic and neurologic sequelae of discontinuation of an antihyperlipidemic drug during ongoing warfarin therapy
Authors: Leonard Charles E. , Brensinger Colleen M. , Bilker Warren B. , Kimmel Stephen E. , Whitaker Heather J. , Hennessy Sean
Published: December 2017

Warfarin and antihyperlipidemics are commonly co-prescribed. Some antihyperlipidemics may inhibit warfarin deactivation via the hepatic cytochrome P450 system. Therefore, antihyperlipidemic discontinuation has been hypothesized to result in underanticoagulation, as warfarin metabolism is no longer inhibited. We quantified the risk of venous thromboembolism (VTE) and ischemic stroke (IS) due to statin and fibrate discontinuation in warfarin users, in which warfarin was initially dose-titrated during ongoing antihyperlipidemic therapy. Using 1999–2011 United States Medicaid claims among 69 million beneficiaries, we conducted a set of bidirectional self-controlled case series studies—one for each antihyperlipidemic. Outcomes were hospital admissions for VTE/IS. The risk segment was a maximum of 90 days immediately following antihyperlipidemic discontinuation, the exposure of interest. Time-varying confounders were included in conditional Poisson models. We identified 629 study eligible-persons with at least one outcome. Adjusted incidence rate ratios (IRRs) for all antihyperlipidemics studied were consistent with the null, and ranged from 0.21 (0.02, 2.82) for rosuvastatin to 2.16 (0.06, 75.0) for gemfibrozil. Despite using an underlying dataset of millions of persons, we had little precision in estimating IRRs for VTE/IS among warfarin-treated persons discontinuing individual antihyperlipidemics. Further research should investigate whether discontinuation of gemfibrozil in warfarin users results in serious underanticoagulation.
Non-invasive multimodal optical coherence and photoacoustic tomography for human skin imaging
Authors: Chen Zhe , Rank Elisabet , Meiburger Kristen M. , Sinz Christoph , Hodul Andreas , Zhang Edward , Hoover Erich , Minneman Micheal , Ensher Jason , Beard Paul C. , Kittler Harald , Leitgeb Rainer A. , Drexler Wolfgang , Liu Mengyang
Published: December 2017

The cutaneous vasculature is involved in many diseases. Current clinical examination techniques, however, cannot resolve the human vasculature with all plexus in a non-invasive manner. By combining an optical coherence tomography system with angiography extension and an all optical photoacoustic tomography system, we can resolve in 3D the blood vessels in human skin for all plexus non-invasively. With a customized imaging unit that permits access to various parts of patients’ bodies, we applied our multimodality imaging system to investigate several different types of skin conditions. Quantitative vascular analysis is given for each of the dermatological conditions to show the potential diagnostic value of our system in non-invasive examination of diseases and physiological processes. Improved performance of our system over its previous generation is also demonstrated with an updated characterization.