bluuebunny/crossref_metadata_2025 huggingface dataset:
Intake of different dietary proteins and risk of type 2 diabetes in men: the Kuopio Ischaemic Heart Disease Risk Factor Study
Authors: Virtanen Heli E. K. , Koskinen Timo T. , Voutilainen Sari , Mursu Jaakko , Tuomainen Tomi-Pekka , Kokko Petra , Virtanen Jyrki K.
Published: April 2017

The roles of different dietary proteins in the aetiology of type 2 diabetes (T2D) remain unclear. We investigated the associations of dietary proteins with the risk of incident T2D in Finnish men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study. The study included 2332 men aged 42–60 years at the baseline examinations in 1984–1989. Protein intakes were calculated from 4-d dietary records. Incident T2D was determined by self-administered questionnaires, fasting blood glucose measurements, 2-h oral glucose tolerance tests, and with national registers. The multivariable-adjusted risk of T2D on the basis of protein intakes was compared by the Cox proportional hazard ratios (HR). During the mean follow-up of 19·3 years, 432 incident T2D cases were identified. Total, animal, meat or dairy product protein intakes were not associated with risk of T2D when the potential confounders were accounted for. Plant (multivariable-adjusted extreme-quartile HR 0·65; 95 % CI 0·42, 1·00; Ptrend 0·04) and egg (HR 0·67; 95 % CI 0·44, 1·00; Ptrend 0·03) protein intakes were associated with a decreased risk of T2D. Adjustments for BMI, plasma glucose and serum insulin slightly attenuated associations. Replacing 1 % energy from carbohydrates with energy from protein was associated with a 5 % (95 % CI 0, 11) increased risk of T2D, but adjustment for fibre intake attenuated the association. Replacing 1 % of energy from animal protein with energy from plant protein was associated with 18 % (95 % CI 0, 32) decreased risk of T2D. This association remained after adjusting for BMI. In conclusion, favouring plant and egg proteins appeared to be beneficial in preventing T2D.
Into the Mainstream or Still at the Margins? 50 Years of Gender Research in the Canadian Political Science Association
Authors: Tolley Erin
Published: April 2017

The annual conference of the Canadian Political Science Association (CPSA) is a disciplinary bellwether that helps us trace the evolution of political science scholarship. This article analyzes research presented at the conference between 1965 and 2015. It shows growth in the gender and politics sub-field and in the presence of women in leadership positions in the CPSA. At the same time, gender-related research is often presented in gender-focused panels and not incorporated across the discipline's sub-fields. This means that gender scholars typically present their work to like-minded researchers, and scholars in other sub-fields have little exposure to gender perspectives. That such siloing occurs at the earliest stages of research dissemination is an important contextual factor in understanding gendered citation patterns, departmental hiring and rates of tenure and promotion. For Canadian political science to remain relevant, more needs to be done to incorporate gender perspectives across the discipline's sub-fields.
La gouvernance francophone de laRevue canadienne de science politiqueet la diffusion des connaissances en français, de 1968 à 2015
Authors: Cardinal Linda , Bernier André
Published: April 2017

LaRevue canadienne de science politique (RCSP)remplit un rôle de premier plan au sein de la communauté scientifique des politologues canadiens et québécois. Elle est l'un des plus importants lieux pour publier les travaux des chercheurs, identifier leurs préoccupations et témoigner des principales tendances au sein de la discipline. Étant donné son engagement envers la dualité linguistique, l'article étudie la représentation francophone au sein de laRCSPdepuis 1968. Qui sont les auteurs qui ont publié leurs travaux en français dans laRevue? D'où viennent-ils ? Quels sont leurs thèmes et domaines de publication ? Est-ce que le fait que cette gouvernance soit concentrée dans trois universités, soit l'Université Laval, l'Université de Montréal et l'Université d'Ottawa, a une incidence importante sur la représentativité des travaux publiés en français ? Bien que de nature exploratoire, l'article révèle que la question de la représentation pose certains enjeux au volet francophone de laRCSPtant sur le plan de sa gouvernance que de la diffusion des travaux des chercheurs.
The Formative Decades of the CPSA
Authors: Newton Janice
Published: April 2017

Drawing on the CPSA's archival records, this article explores the origins of CPSA and the patterns of representation in its founding decades. We focus on the pre-World War II years, when disciplinary boundaries were fluid and scholars sought to shift policy discussion from moral reform to reform guided by science and professionalism. The CPSA's founding vision aspired to engage “typical citizens” in discussion of current issues. Despite the ambitious vision, a much narrower range of citizens participated. The CPSA's powerful melding of academic, corporate, state and political elites, in turn, shaped the CPSA's reflections on the development of the Canadian state and public policy. This historical legacy encourages us to reflect on the contemporary challenges of fostering independent scholarship on public issues.
Le politique, l’État et les idéologies : le point de vue québécois
Authors: Boily Frédéric
Published: April 2017

Dans un numéro de la revuePolitiqueconsacré à l’évolution de la discipline au Québec, un auteur notait que les articles réunis à cette occasion ne recouvraient pas tous les champs de la science politique québécoise (Landry, 1993: 7–19). La théorie politique, comprise au sens large du terme, avait notamment été délaissée au profit d’études sur les politiques publiques et les institutions. Or, à l'instar de leurs collègues ailleurs au pays, les politologues québécois ont pourtant réfléchi aux questions politiques en y apportant un regard théorique ancré dans une réalité sociale particulière différente de celle prévalant au Canada anglais. Désireux de mieux comprendre l’évolution de leur société, des politologues ont privilégié quelques objets d'analyse dont celui de l’État et de la nature des idéologies politiques québécoises.
Les études électorales au Québec depuis 1970 ou l'analyse de l'exceptionnalisme québécois aux urnes
Authors: Chouinard Stéphanie
Published: April 2017

Les élections générales de 1970 au Québec ont marqué tant les esprits que la discipline de la science politique au Québec, en particulier les analyses s'intéressant au comportement électoral et à l’étude des partis. En effet, pour la première fois de l'histoire de la province, un parti indépendantiste, le Parti québécois (PQ), faisait son entrée à l'Assemblée nationale, « un réalignement important des divisions partisanes » (Lemieux, 1976a : 60) remettant en question le bipartisme tenace de l’échiquier politique québécois. Cette élection, ainsi que celle de 1973, ont aussi illuminé les défauts du mode de scrutin majoritaire uninominal à un tour (MU1), le PQ récoltant respectivement 7 sièges pour 23% du vote et 6 sièges pour 30% du vote–frustrant une grande partie de l’électorat.
TEMPORARY REFUGE FROM WAR: CUSTOMARY INTERNATIONAL LAW AND THE SYRIAN CONFLICT
Authors: Lambert Hélène
Published: April 2017

The rule of temporary refuge forms the cornerstone of the response of States to large-scale influx of refugees. In the context of civilians fleeing armed conflict, this legal rule imposes a positive obligation onallStates to admit and not to return anyone to a situation where there is a risk to life, and to provide basic rights commensurate with human dignity. Also implicit in the rule is the expectation of shared responsibility for large numbers of refugees and of international cooperation towards finding durable solutions. This article examines the customary international law of temporary refuge (also known as temporary protection) in relation to the Syrian conflict. It discusses implementation of the rule in the practice of three countries neighbouring Syria, and in the EU. It finds that the practice of Turkey, Lebanon and Jordan has been consistent with the rule of temporary refuge. However, the EU has decided not to use the Temporary Protection Directive; instead individual Member States have relied on the Refugee Convention and EU law, combined with various other measures not pertinent to temporary protection. It is concluded that shared responsibility is the linchpin of temporary refuge. Absent this keystone, the rule of temporary refuge is likely to continue to be implemented primarily in a regional context by those countries nearest to the country affected by the conflict, as in the case of Syria.
Philometra saltatrix (Nematoda: Philometridae) in the ovary of the bluefish, Pomatomus saltatrix (Linnaeus, 1766), off the coast of the state of Rio de Janeiro, Brazil
Authors: São Clemente S.C. , Felizardo N.N. , Ferreira M.F. , Menezes R.C. , Cunha N.C. , Aguiar F.C.C. , Nascimento E.R. , Telleria E.L. , Tortelly R. , Knoff M.
Published: April 2017

The aims of the present study were to identify and describe the occurrence of nematode parasites in the gonads of bluefish Pomatomus saltatrix from off the coast of the state of Rio de Janeiro, Brazil. Only females were found to be parasitized by the nematodes, which were identified as P. saltatrix using morphological, morphometric and molecular data. Infection of female bluefish by this nematode had the following values: prevalence, 48.7%; mean intensity, 2.6; mean abundance, 1.3; and range of infection, 1–10 specimens. Histopathological examination of transverse and longitudinal sections of the parasitized ovaries showed nematodes at different stages of development among oocytes, but no indication of any associated inflammatory reaction. The presence of nematodes in the ovaries of bluefish is an important indication of fish hygiene, and parasitized fish are usually rejected by consumers because of their repugnant appearance.
Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors
Authors: Demjaha A. , Lappin J. M. , Stahl D. , Patel M. X. , MacCabe J. H. , Howes O. D. , Heslin M. , Reininghaus U. A. , Donoghue K. , Lomas B. , Charalambides M. , Onyejiaka A. , Fearon P. , Jones P. , Doody G. , Morgan C. , Dazzan P. , Murray R. M.
Published: April 2017

Background

We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.

Method

The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.

Results

From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.

Conclusions

The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.
Clarifying the role of neuroticism in suicidal ideation and suicide attempt among women with major depressive disorder
Authors: Rappaport L. M. , Flint J. , Kendler K. S.
Published: April 2017

Background

Prior research consistently demonstrates that neuroticism increases risk for suicidal ideation, but the association between neuroticism and suicidal behavior has been inconsistent. Whereas neuroticism is recommended as an endophenotype for suicidality, the association of neuroticism with attempted suicide warrants clarification. In particular, prior research has not distinguished between correlates of attempted suicide, correlates of suicidal ideation, and correlates of comorbid psychopathology.

Methods

The present study used the CONVERGE study, a sample of 5864 women with major depressive disorder (MD) and 5783 women without MD throughout China. Diagnoses, suicidal ideation, and attempted suicide were assessed with the Composite International Diagnostic Interview (CIDI). Neuroticism was assessed with the neuroticism portion of the Eysenck Personality Questionnaire.

Results

Results replicate prior findings on the correlates of suicidal ideation, particularly elevated neuroticism among individuals who report prior suicidal ideation. Moreover, as compared with individuals who reported having experienced only suicidal ideation, neuroticism was associated with decreased likelihood of having attempted suicide.

Conclusions

The association of neuroticism with suicidality is more complicated than has been previously described. Whereas neuroticism increases risk for suicidal ideation, neuroticism may decrease risk for a suicide attempt among individuals with suicidal ideation. These results have implications for the assessment of risk for a suicide attempt among individuals who report suicidal ideation and addresses prior discordant findings by clarifying the association between neuroticism and attempted suicide.
CHARACTERISTIC FUNCTION BASED TESTING FOR CONDITIONAL INDEPENDENCE: A NONPARAMETRIC REGRESSION APPROACH
Authors: Wang Xia , Hong Yongmiao
Published: April 2017

We propose a characteristic function based test for conditional independence, applicable to both cross-sectional and time series data. We also derive a class of derivative tests, which deliver model-free tests for such important hypotheses as omitted variables, Granger causality in various moments and conditional uncorrelatedness. The proposed tests have a convenient asymptotic nullN(0, 1) distribution, and are asymptotically locally more powerful than a variety of related smoothed nonparametric tests in the literature. Unlike other smoothed nonparametric tests for conditional independence, we allow nonparametric estimators for both conditional joint and marginal characteristic functions to jointly determine the asymptotic distributions of the test statistics. Monte Carlo studies demonstrate excellent power of the tests against various alternatives. In an application to testing Granger causality, we document the existence of nonlinear relationships between money and output, which are missed by some existing tests.
Can Science Feed on a Crisis? Expectations, the Pine Institute, and the Decline of the French Resin Industry
Authors: Krasnodębski Marcin
Published: April 2017

Argument

While science and economy are undoubtedly interwoven, the nature of their relationship is often reduced to a positive correlation between economic and scientific prosperity. It seems that the modern scholarship focusing on “success stories” tends to neglect counterintuitive examples such as the impact of economic crises on research. We argue that economic difficulties, under certain circumstances, may also lead to the prosperous development of scientific institutions. This paper focuses on a particular organism, the Pine Institute in Bordeaux in France. Not only was it a key actor in the process of defining the discipline of resin chemistry, but also it remained for years at the heart of the local resin producing industry. Interestingly, there is an actual inverse correlation between the Institute's budgets and the prices and production of resinous products. The Pine Institute's existence seemed to have been driven by the crisis of the resin industry.
Archaeology, historical ecology and anthropogenic island ecosystems
Authors: BRAJE TODD J. , LEPPARD THOMAS P. , FITZPATRICK SCOTT M. , ERLANDSON JON M.
Published: April 2017

In the face of environmental uncertainty due to anthropogenic climate change, islands are at the front lines of global change, threatened by sea level rise, habitat alteration, extinctions and declining biodiversity. Islands also stand at the forefront of scientific study for understanding the deep history of human ecodynamics and to build sustainable future systems. We summarize the long history of human interactions with Polynesian, Mediterranean, Californian and Caribbean island ecosystems, documenting the effects of various waves of human settlement and socioeconomic systems, from hunter–gatherer–fishers, to agriculturalists, to globalized colonial interests. We identify degradation of island environments resulting from human activities, as well as cases of human management of resources to enhance productivity and create more sustainable systems. These case studies suggest that within a general global pattern of progressive island degradation, there was no single trajectory of human impact, but rather complex effects based on variable island physiographies, human subsistence strategies, population densities, technologies, sociopolitical organization and decision-making.
Influence of agro-ecological service crop termination and synthetic biodegradable film covering on Aphis gossypii Glover (Rhynchota: Aphididae) infestation and natural enemy dynamics
Authors: Magagnoli Serena , Depalo Laura , Masetti Antonio , Campanelli Gabriele , Canali Stefano , Leteo Fabrizio , Burgio Giovanni
Published: April 2017

Agro-ecological service crops (ASC) can increase the vegetation complexity of agroecosystems leading to a positive impact on natural enemies of arthropod pests and on weed control. In this study, two ASC terminations (green manure and roller crimper) and a Mater-Bi-mulched control (MB) were compared in order to describe the effects on pests and beneficial dynamics in an organic vegetable system. The trials were conducted over two consecutive growing seasons in 2014 and 2015. Zucchini were grown as cash crop and barley as ASC. Pests and natural enemies were monitored fortnightly by visual samplings along the whole zucchini-growing season. Zucchini plants showed a faster vegetative growth in MB treatment than in ASC terminations. In both years, MB plots were characterized by higher soil temperature and higher leaf nitrogen concentration resulting in plants more susceptible to Aphis gossypii infestations. In all the experimental plots, natural enemies controlled aphid infestations and no insecticide and sprays were necessary. In conclusion, the tested ASC techniques have been suggested as a tool to mitigate aphid infestation.
Erratum: Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro
Authors: Wu Yaoxing , Liu Qingxiang , Zhou Jie , Xie Weihong , Chen Cheng , Wang Zefang , Yang Haitao , Cui Jun
Published: April 2017

Correction to: Cell Discovery (2017) 3, 17006; doi:10.1038/celldisc.2017.6; published online 21 March 2017 In the initial published version of this article, a mistake was made in the affiliation 1, where ‘Sun Yat-sen University’ should be added after the School of Life Sciences. The corrected affiliation 1 is displayed below.
Chemical biology reveals CARF as a positive regulator of canonical Wnt signaling by promoting TCF/β-catenin transcriptional activity
Authors: He Xiaoli , Zhang Wenjuan , Yan Chen , Nie Fen , Li Chen , Liu Xiaofen , Fei Cong , Li Shengdi , Song Xiaomin , Jia Yingying , Zeng Rong , Wu Dianqing , Pan Weijun , Hao Xiaojiang , Li Lin
Published: April 2017

Wnt/β-catenin signaling regulates multiple biological processes and aberration of this pathway is frequently observed in human cancers. Previously, we uncovered NC043 as a small-molecule inhibitor of Wnt/β-catenin signaling. Here, we identified CARF as the cellular target of NC043. We found that NC043 binds directly to CARF through forming a covalent bond with the Cys-516 residue of CARF. Further study revealed that CARF interacts with Dvl, which potentiates the Dvl–c-Jun–β-catenin–TCF transcriptional complex and thus promotes Wnt signaling activation. NC043 could disrupt the interaction between CARF and Dvl, thereby impairing Wnt signal transduction. In line with this, knockdown of CARF in zebrafish leads to impairment of embryonic development, hematopoietic stem cell generation and caudal fin regeneration. Collectively, we identified CARF as the cellular target of NC043 and revealed CARF as a positive regulator of Wnt/β-catenin signal transduction.
Signals of vagal circuits engaging with AKT1 in α7 nAChR+CD11b+ cells lessen E. coli and LPS-induced acute inflammatory injury
Authors: Zhao Caiqi , Yang Xi , Su Emily M , Huang Yuanyuan , Li Ling , Matthay Michael A , Su Xiao
Published: April 2017

Vagal circuits-α7 nAChR (α7 nicotinic acetylcholine receptor, coded byChrna7) signaling utilizes spleen as a hub to dampen systemic inflammatory responses. Vagal innervations also extend to the distal airways and alveoli. Vagotomy and deficiency of α7 nAChR deteriorateE. coliand lipopolysaccharide (LPS)-induced acute lung inflammatory responses; however, the underlying mechanisms remain elusive. Here, we hypothesized that vagal circuits would limit splenic release and lung recruitment of α7 nAChR+CD11b+cells (CD11b is coded byItgam, a surface marker of monocytes and neutrophils) via phosphorylation of AKT1 and that this process would define the severity of lung injury. Using bothE. coliand LPS-induced lung injury mouse models, we found that vagotomy augmented splenic egress and lung recruitment of α7 nAChR+CD11b+cells, and consequently worsened lung inflammatory responses. Rescue of vagotomy with an α7 nAChR agonist preserved α7 nAChR+CD11b+cells in the spleen, suppressed recruitment of these cells to the lung and attenuated lung inflammatory responses. Vagal signals via α7 nAChR promoted serine473 phosphorylation of AKT1 in α7 nAChR+CD11b+cells and stabilized these cells in the spleen. Deletion ofAkt1enhanced splenic egress and lung recruitment of α7 nAChR+CD11b+cells, which elicited neutrophil-infiltrated lung inflammation and injury. Vagotomy and double deletion ofChrna7andItgamreduced serine473 phosphorylation of AKT1 in the spleen and BAL (bronchoalveolar lavage) Ly6CintGr1hineutrophils and Ly6Chimonocytes, and they facilitated the recruitment of neutrophils and monocytes to the airspaces ofE. coli-injured lungs. Double deletion ofChrna7andItgamincreased lung recruitment of monocytes and/or neutrophils and deterioratedE. coliand LPS-induced lung injury. Thus, signals of vagal circuits engaging with AKT1 in α7 nAChR+CD11b+cells attenuateE. coliand LPS-induced acute lung inflammatory responses. Targeting this signaling pathway could provide novel therapeutic strategies for treating acute lung injury.
Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer
Authors: Xue Mengzhu , Liu Haiyue , Zhang Liwen , Chang Hongyuan , Liu Yuwei , Du Shaowei , Yang Yingqun , Wang Peng
Published: April 2017

Androgen-ablation therapies, which are the standard treatment for metastatic prostate cancer, invariably lead to acquired resistance. Hence, a systematic identification of additional drivers may provide useful insights into the development of effective therapies. Numerous microRNAs that are critical for metastasis are dysregulated in metastatic prostate cancer, but the underlying molecular mechanism is poorly understood. We perform an integrative analysis of transcription factor (TF) and microRNA expression profiles and computationally identify three master TFs, AR, HOXC6 and NKX2-2, which induce the aberrant metastatic microRNA expression in a mutually exclusive fashion. Experimental validations confirm that the three TFs co-dysregulate a large number of metastasis-associated microRNAs. Moreover, their overexpression substantially enhances cell motility and is consistently associated with a poor clinical outcome. Finally, the mutually exclusive overexpression between AR, HOXC6 and NKX2-2 is preserved across various tissues and cancers, suggesting that mutual exclusivity may represent an intrinsic characteristic of driver TFs during tumorigenesis.
A microprocessor based on a two-dimensional semiconductor
Authors: Wachter Stefan , Polyushkin Dmitry K. , Bethge Ole , Mueller Thomas
Published: April 2017

The advent of microcomputers in the 1970s has dramatically changed our society. Since then, microprocessors have been made almost exclusively from silicon, but the ever-increasing demand for higher integration density and speed, lower power consumption and better integrability with everyday goods has prompted the search for alternatives. Germanium and III–V compound semiconductors are being considered promising candidates for future high-performance processor generations and chips based on thin-film plastic technology or carbon nanotubes could allow for embedding electronic intelligence into arbitrary objects for the Internet-of-Things. Here, we present a 1-bit implementation of a microprocessor using a two-dimensional semiconductor—molybdenum disulfide. The device can execute user-defined programs stored in an external memory, perform logical operations and communicate with its periphery. Our 1-bit design is readily scalable to multi-bit data. The device consists of 115 transistors and constitutes the most complex circuitry so far made from a two-dimensional material.
MicroRNA miR-23a cluster promotes osteocyte differentiation by regulating TGF-β signalling in osteoblasts
Authors: Zeng Huan-Chang , Bae Yangjin , Dawson Brian C. , Chen Yuqing , Bertin Terry , Munivez Elda , Campeau Philippe M. , Tao Jianning , Chen Rui , Lee Brendan H.
Published: April 2017

Osteocytes are the terminally differentiated cell type of the osteoblastic lineage and have important functions in skeletal homeostasis. Although the transcriptional regulation of osteoblast differentiation has been well characterized, the factors that regulate differentiation of osteocytes from mature osteoblasts are poorly understood. Here we show that miR-23a∼27a∼24-2 (miR-23a cluster) promotes osteocyte differentiation. Osteoblast-specific miR-23a cluster gain-of-function mice have low bone mass associated with decreased osteoblast but increased osteocyte numbers. By contrast, loss-of-function transgenic mice overexpressing microRNA decoys for either miR-23a or miR-27a, but not miR24-2, show decreased osteocyte numbers. Moreover, RNA-sequencing analysis shows altered transforming growth factor-β (TGF-β) signalling. Prdm16, a negative regulator of the TGF-β pathway, is directly repressed by miR-27a with concomitant alteration of sclerostin expression, and pharmacological inhibition of TGF-β rescues the phenotypes observed in the gain-of-function transgenic mice. Taken together, the miR-23a cluster regulates osteocyte differentiation by modulating the TGF-β signalling pathway through targeting of Prdm16.
Erratum: Connecting genetic risk to disease end points through the human blood plasma proteome
Authors: Suhre Karsten , Arnold Matthias , Bhagwat Aditya Mukund , Cotton Richard J. , Engelke Rudolf , Raffler Johannes , Sarwath Hina , Thareja Gaurav , Wahl Annika , DeLisle Robert Kirk , Gold Larry , Pezer Marija , Lauc Gordan , El-Din Selim Mohammed A. , Mook-Kanamori Dennis O. , Al-Dous Eman K. , Mohamoud Yasmin A. , Malek Joel , Strauch Konstantin , Grallert Harald , Peters Annette , Kastenmüller Gabi , Gieger Christian , Graumann Johannes
Published: April 2017

Nature Communications 8: Article number: 14357 (2017); Published 27 February 2017; Updated 11 April 2017 The original version of the Supplementary Information attached to this Article did not include Supplementary Note 1 The HTML has now been updated to include a corrected version of the Supplementary Information.
The impact of host sex on the outcome of co-infection
Authors: Thompson Olivia , Gipson Stephen A. Y. , Hall Matthew D.
Published: April 2017

Males and females vary in many characteristics that typically underlie how well a host is able to fight infection, such as body-size, immune capacity, or energy availability. Although well studied in the context of sexual signalling, there is now growing recognition that these differences can influence aspects of pathogen evolution as well. Here we consider how co-infection between multiple pathogen strains is shaped by male-female differences. In natural populations, infections by more than one pathogen strain or species are believed to be a widespread occurrence. Using the water flea, Daphnia magna, we exposed genetically identical males and females to replicated bacterial co-infections. We found that pathogen transmission and virulence were much higher in females. However, males did not simply lower average pathogen fitness, but rather the influence of co-infection was more varied and less defined than in females. We discuss how pathogens may have more fitness benefits to gain, and consequently to lose, when infecting one sex over the other.
Strain softening of nano-scale fuzzy interfaces causes Mullins effect in thermoplastic polyurethane
Authors: Sui T. , Salvati E. , Ying S. , Sun G. , Dolbnya I. P. , Dragnevski K. , Prisacariu C. , Korsunsky A. M.
Published: April 2017

The strain-induced softening of thermoplastic polyurethane elastomers (TPUs), known as the Mullins effect, arises from their multi-phase structure. We used the combination of small- and wide- angle X-ray scattering (SAXS/WAXS) during in situ repeated tensile loading to elucidate the relationship between molecular architecture, nano-strain, and macro-scale mechanical properties. Insights obtained from our analysis highlight the importance of the ‘fuzzy interface’ between the hard and soft regions that governs the structure evolution at nanometre length scales and leads to macroscopic stiffness reduction. We propose a hierarchical Eshelby inclusion model of phase interaction mediated by the ‘fuzzy interface’ that accommodates the nano-strain gradient between hard and soft regions and undergoes tension-induced softening, causing the Mullins effect that becomes apparent in TPUs even at moderate tensile strains.
A lack of coordination between sister-chromatids segregation and cytokinesis in the oocytes of B6.YTIR (XY) sex-reversed female mice
Authors: Zhu Jia-Qiao , Tan Seang Lin , Taketo Teruko
Published: April 2017

The B6.YTIR (XY) mouse develops bilateral ovaries despite the expression of the testis-determining gene Sry during gonadal differentiation. We reported that the oocytes of the XY female are defective in their cytoplasm, resulting in a failure in the second meiotic division after activation or fertilization in vitro. However, the mechanism of meiotic failure or the cause of infertility remained to be clarified. In the present study, we obtained mature oocytes from XY females by superovulation and confirmed that these oocytes also fail in zygotic development. By using confocal microscopy 3D-analysis, we demonstrated that meiotic spindles were properly positioned and oriented in the MII-oocytes from XY females. After parthenogenic activation, fewer oocytes from XY females extruded the second polar body, and in those oocytes, sister-chromatids were often separated but neither set entered the second polar body. ARP2, F-actin, and ORC4, known to play roles in asymmetric meiotic division, were initially localized along the ooplasmic membrane and concentrated over the MII-spindle but lost their cortical polarity after activation while the sister-chromatids moved away from the oolemma in the oocytes from XY females. Our results indicate that the second polar body extrusion is uncoupled from the sister-chromatids separation in the oocytes from XY female mouse.
Dietary behaviour of man-eating lions as revealed by dental microwear textures
Authors: DeSantis Larisa R. G. , Patterson Bruce D.
Published: April 2017

Lions (Panthera leo) feed on diverse prey species, a range that is broadened by their cooperative hunting. Although humans are not typical prey, habitual man-eating by lions is well documented. Fathoming the motivations of the Tsavo and Mfuwe man-eaters (killed in 1898 in Kenya and 1991 in Zambia, respectively) may be elusive, but we can clarify aspects of their behaviour using dental microwear texture analysis. Specifically, we analysed the surface textures of lion teeth to assess whether these notorious man-eating lions scavenged carcasses during their depredations. Compared to wild-caught lions elsewhere in Africa and other large feliforms, including cheetahs and hyenas, dental microwear textures of the man-eaters do not suggest extreme durophagy (e.g. bone processing) shortly before death. Dental injuries to two of the three man-eaters examined may have induced shifts in feeding onto softer foods. Further, prompt carcass reclamation by humans likely limited the man-eaters’ access to bones. Man-eating was likely a viable alternative to hunting and/or scavenging ungulates due to dental disease and/or limited prey availability.
Luciferase-Specific Coelenterazine Analogues for Optical Contamination-Free Bioassays
Authors: Nishihara Ryo , Abe Masahiro , Nishiyama Shigeru , Citterio Daniel , Suzuki Koji , Kim Sung Bae
Published: April 2017

Spectral overlaps among the multiple optical readouts commonly cause optical contamination in fluorescence and bioluminescence. To tackle this issue, we created five-different lineages of coelenterazine (CTZ) analogues designed to selectively illuminate a specific luciferase with unique luciferase selectivity. In the attempt, we found that CTZ analogues with ethynyl or styryl groups display dramatically biased bioluminescence to specific luciferases and pHs by modifying the functional groups at the C-2 and C-6 positions of the imidazopyradinone backbone of CTZ. The optical contamination-free feature was exemplified with the luciferase-specific CTZ analogues, which illuminated anti-estrogenic and rapamycin activities in a mixture of optical probes. This unique bioluminescence platform has great potential for specific and high throughput imaging of multiple optical readouts in bioassays without optical contamination.
The prevalence of thalassemia in mainland China: evidence from epidemiological surveys
Authors: Lai Ketong , Huang Guifeng , Su Li , He Yunyan
Published: April 2017

Comprehensive data regarding the epidemiology and prevalence of thalassemia in mainland China are lacking. To assess the prevalence of thalassemia, we performed a meta-analysis including 16 articles published from 1981 to 2015. The overall prevalence of α-thalassemia, β-thalassemia and α + β-thalassemia was 7.88%, 2.21% and 0.48%, respectively. Trends in thalassemia prevalence in mainland China were not steady; a prevalence map based on a geographic information system (GIS) showed that the geographic distribution of thalassemia was highest in the south of China and decreased from south to north. Additionally, the most common α- and β-globin gene mutation was --SEA and CD41/42, respectively. The current study provides valuable information regarding epidemiology and intervention and supports the planning, implementation and management of prevention programmes for public health.
Regulation of intraocular pressure by microRNA cluster miR-143/145
Authors: Li Xinyu , Zhao Fangkun , Xin Mei , Li Guorong , Luna Coralia , Li Guigang , Zhou Qinbo , He Yuguang , Yu Bo , Olson Eric , Gonzalez Pedro , Wang Shusheng
Published: April 2017

Glaucoma is a major cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP), which causes optic nerve damage and retinal ganglion cell death, is the primary risk factor for blindness in glaucoma patients. IOP is controlled by the balance between aqueous humor secretion from the ciliary body (CB) and its drainage through the trabecular meshwork (TM). How microRNAs (miRs) regulate IOP and glaucoma in vivo is largely unknown. Here we show that miR-143 and miR-145 expression is enriched in the smooth muscle and trabecular meshwork in the eye. Targeted deletion of miR-143/145 in mice results in significantly reduced IOP, consistent with an ~2-fold increase in outflow facilities. However, aqueous humor production in the same mice appears to be normal based on a microbeads-induced glaucoma model. Mechanistically, we found that miR-143/145 regulates actin dynamics and the contractility of TM cells, consistent with its regulation of actin-related protein complex (ARPC) subunit 2, 3, and 5, as well as myosin light chain kinase (MLCK) in these cells. Our data establish miR-143/145 as important regulators of IOP, which may have important therapeutic implications in glaucoma.
Thermally Triggered Mechanically Destructive Electronics Based On Electrospun Poly(ε-caprolactone) Nanofibrous Polymer Films
Authors: Gao Yang , Sim Kyoseung , Yan Xin , Jiang Jiang , Xie Jingwei , Yu Cunjiang
Published: April 2017

Electronics, which functions for a designed time period and then degrades or destructs, holds promise in medical implants, reconfigurable electronic devices and/or temporary functional systems. Here we report a thermally triggered mechanically destructive device, which is constructed with an ultra-thin electronic components supported by an electrospun poly(ε-caprolactone) nanofibrous polymer substrate. Upon heated over the melting temperature of the polymer, the pores of the nanofibers collapse due to the nanofibers’ microscopic polymer chain relaxing and packing. As a result, the polymer substrate exhibits approximately 97.5% area reduction. Ultra-thin electronic components can therefore be destructed concurrently. Furthermore, by integrating a thin resistive heater as the thermal trigger of Joule heating, the device is able to on-demand destruct. The experiment and analytical results illustrate the essential aspects and theoretical understanding for the thermally triggered mechanical destructive devices. The strategy suggests a viable route for designing destructive electronics.
Response of peanut Arachis hypogaea roots to the presence of beneficial and pathogenic fungi by transcriptome analysis
Authors: Hao Kun , Wang Feng , Nong Xiangqun , McNeill Mark Richard , Liu Shaofang , Wang Guangjun , Cao Guangchun , Zhang Zehua
Published: April 2017

Entomopathogenic fungus Metarhizium anisopliae obtain survival benefit meanwhile promote the nutrient absorption of root as an endophyte. However, little is known concerning molecular mechanisms in the process. We performed the transcriptome sequencing of A. hypogaea roots inoculated M. anisopliae and pathogenic Fusarium axysporum, respectively. There were 81323 unigenes from 132023 transcripts. Total 203 differentially expressed genes (DEGs) respond to the two fungi, including specific 76 and 34 DEGs distributed respectively in M. anisopliae and F. axysporum treatment. KEGG pathway enrichment for DEGs showed the two top2 were signal transductions of plant-pathogen interaction and plant hormone. By qRT-PCR, the mRNA level of 26 genes involved in plant-fungus interaction confirmed the reliability of the RNA-Seq data. The expression pattern of the key DEGs on jasmonic acid (JA) or salicylic acid (SA) signaling pathway presented regulating consistency with JA or SA concentration detected by HPLC-MS. Those significantly stronger down-regulated DEGs by M. anisopliae thanby F. axysporum linking to hypersensitive response and negative regulation of defense, and those specific up-regulated genes in M. anisopliae treatment may predict that the less immunity is conducive to symbiosis F. axysporum may trigger JA-mediated defense regulated by ERF branch of JA signaling pathway, whereas M. anisopliae does not.
The Chemical Characterization of Nigerian Propolis samples and Their Activity Against Trypanosoma brucei
Authors: Omar Ruwida , Igoli John O. , Zhang Tong , Gray Alexander I. , Ebiloma Godwin U. , Clements Carol J. , Fearnley James , Edrada Ebel RuAngeli , Paget Tim , de Koning Harry P. , Watson David G.
Published: April 2017

Profiling of extracts from twelve propolis samples collected from eight regions in Nigeria was carried out using high performance liquid chromatography (LC) coupled with evaporative light scattering (ELSD), ultraviolet detection (UV) and mass spectrometry (MS), gas chromatography mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). Principal component analysis (PCA) of the processed LC-MS data demonstrated the varying chemical composition of the samples. Most of the samples were active against Trypanosoma b. brucei with the highest activity being in the samples from Southern Nigeria. The more active samples were fractionated in order to isolate the component(s) responsible for their activity using medium pressure liquid chromatography (MPLC). Three xanthones, 1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone, 1,3,7-trihydroxy-4,8-di-(3-methylbut-2-enyl)xanthone a previously undescribed xanthone and three triterpenes: ambonic acid, mangiferonic acid and a mixture of α-amyrin with mangiferonic acid (1:3) were isolated and characterised by NMR and LC-MS. These compounds all displayed strong inhibitory activity against T.b. brucei but none of them had higher activity than the crude extracts. Partial least squares (PLS) modelling of the anti-trypanosomal activity of the sample extracts using the LC-MS data indicated that high activity in the extracts, as judged from LCMS2 data, could be correlated to denticulatain isomers in the extracts.
A sublethal dose of a neonicotinoid insecticide disrupts visual processing and collision avoidance behaviour in Locusta migratoria
Authors: Parkinson Rachel H. , Little Jacelyn M. , Gray John R.
Published: April 2017

Neonicotinoids are known to affect insect navigation and vision, however the mechanisms of these effects are not fully understood. A visual motion sensitive neuron in the locust, the Descending Contralateral Movement Detector (DCMD), integrates visual information and is involved in eliciting escape behaviours. The DCMD receives coded input from the compound eyes and monosynaptically excites motorneurons involved in flight and jumping. We show that imidacloprid (IMD) impairs neural responses to visual stimuli at sublethal concentrations, and these effects are sustained two and twenty-four hours after treatment. Most significantly, IMD disrupted bursting, a coding property important for motion detection. Specifically, IMD reduced the DCMD peak firing rate within bursts at ecologically relevant doses of 10 ng/g (ng IMD per g locust body weight). Effects on DCMD firing translate to deficits in collision avoidance behaviours: exposure to 10 ng/g IMD attenuates escape manoeuvers while 100 ng/g IMD prevents the ability to fly and walk. We show that, at ecologically-relevant doses, IMD causes significant and lasting impairment of an important pathway involved with visual sensory coding and escape behaviours. These results show, for the first time, that a neonicotinoid pesticide directly impairs an important, taxonomically conserved, motion-sensitive visual network.
[18F]tetrafluoroborate-PET/CT enables sensitive tumor and metastasis in vivo imaging in a sodium iodide symporter-expressing tumor model
Authors: Diocou S. , Volpe A. , Jauregui-Osoro M. , Boudjemeline M. , Chuamsaamarkkee K. , Man F. , Blower P. J. , Ng T. , Mullen G. E. D. , Fruhwirth G. O.
Published: April 2017

Cancer cell metastasis is responsible for most cancer deaths. Non-invasive in vivo cancer cell tracking in spontaneously metastasizing tumor models still poses a challenge requiring highest sensitivity and excellent contrast. The goal of this study was to evaluate if the recently introduced PET radiotracer [18F]tetrafluoroborate ([18F]BF4−) is useful for sensitive and specific metastasis detection in an orthotopic xenograft breast cancer model expressing the human sodium iodide symporter (NIS) as a reporter. In vivo imaging was complemented by ex vivo fluorescence microscopy and γ-counting of harvested tissues. Radionuclide imaging with [18F]BF4− (PET/CT) was compared to the conventional tracer [123I]iodide (sequential SPECT/CT). We found that [18F]BF4− was superior due to better pharmacokinetics, i.e. faster tumor uptake and faster and more complete clearance from circulation. [18F]BF4−-PET was also highly specific as in all detected tissues cancer cell presence was confirmed microscopically. Undetected comparable tissues were similarly found to be free of metastasis. Metastasis detection by routine metabolic imaging with [18F]FDG-PET failed due to low standard uptake values and low contrast caused by adjacent metabolically active organs in this model. [18F]BF4−-PET combined with NIS expressing disease models is particularly useful whenever preclinical in vivo cell tracking is of interest.
Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice
Authors: Crawford Lindsey B. , Tempel Rebecca , Streblow Daniel N. , Kreklywich Craig , Smith Patricia , Picker Louis J. , Nelson Jay A. , Caposio Patrizia
Published: April 2017

The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our understanding of antiviral adaptive immune responses in the context of a human immune system. We have previously shown that HCMV infection of human hematopoietic progenitor cells engrafted in immune deficient mice (huNSG) results in viral latency that can be reactivated following G-CSF treatment. In this study, we characterized the functional human adaptive immune responses in HCMV latently-infected huBLT (humanized Bone marrow-Liver-Thymus) mice. Following infection, huBLT mice generate human effector and central memory CD4+ and CD8+ T-cell responses reactive to peptides corresponding to both IE and pp65 proteins. Additionally, both HCMV specific IgM and IgG B-cell responses with the ability to neutralize virus were detected. These results indicate that the HCMV huBLT mouse model may provide a valuable tool to study viral latency and reactivation as well as evaluate HCMV vaccines and immune responses in the context of a functional human immune system.
Paraquat poisoning induced pulmonary epithelial mesenchymal transition through Notch1 pathway
Authors: Li Tiegang , Yang Xiangming , Xin Shiyu , Cao Yan , Wang Nana
Published: April 2017

Progressive pulmonary fibrosis is the most characteristic feature of subacute PQ poisoning. Epithelial-to-mesenchymal transition (EMT) is reported to be involved in the pulmonary fibrosis after PQ exposure. Recent evidence suggested Notch signaling is required for EMT. In this study, we investigated whether Notch1 and TGF-β1/Smad3 signaling was involved in EMT caused by PQ. It is demonstrated that A549 cells underwent EMT after treated with PQ at dose of 300 μmol/L for 6 days, charactered by increasing expression of mesenchymal marker α-SMA and decreasing expression of epithelial marker E-cadherin. We found that there was an apparent increased expression of Notch1 and jagged-1 in PQ induced EMT process. EMT could be enhanced by Jagged-1 ligand of Notch1, and be blocked by DAPT, a γ-secretase inhibitor. Our data also showed that the expression of TGF-β1/Smad3 increased after Notch1 is elevated in EMT caused by PQ. Jagged-1 significantly induced SMA expression, and this induction was completely inhibited by SB431542 in A549 cells. In conclusion, we demonstrated that Notch1 pathway was important in EMT induced by PQ, and TGF-β1/Smad3 signaling partly plays a role as the downstream of Notch1.