bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of epicardial fat thickness with clinical and polysomnographic parameters in non-obese obstructive sleep apnoea patients
Authors: Derin S , Altun I , Koseoglu S , Sahin C , Yilmaz M , Akin F , Sahan M
Published: April 2018

Objectives:

This study aimed to investigate the relationship of epicardial fat thickness with severity of obstructive sleep apnoea, and clinical and polysomnographic parameters, and to determine independent predictors for epicardial fat thickness.

Methods:

A total of 84 patients with a body mass index of less than 30 kg/m2 and suspected sleep-disordered breathing were included in the study. The correlations of epicardial fat thickness with polysomnographic and clinical data, and severity of obstructive sleep apnoea, were investigated.

Results:

Mean epicardial fat thickness was 3.75 ± 1.07 mm in the study group (n = 62) and 2.97 ± 0.62 mm in the control group (n = 22) (p < 0.001). There were significant positive correlations between epicardial fat thickness and: apnoea/hypopnoea index, oxygen desaturation index 3 and minimum oxygen saturation, as well as with age, body mass index, and neck and waist circumferences.

Conclusion:

Non-obese obstructive sleep apnoea patients have thicker epicardial fat compared to controls. Oxygen desaturation index 3 has a strong correlation with epicardial fat thickness and is an independent predictor of it.
‘What a Picture Can Do’: Contests of colonial mastery in photographs of Asian ‘houseboys’ from Southeast Asia and Northern Australia, 1880s–1920s
Authors: LOWRIE CLAIRE
Published: April 2018

The archives of colonial Southeast Asia and northern Australia contain hundreds of photographs of masterly white colonizers and their seemingly devoted Asian ‘houseboys’. This article analyses this rich photographic archive, drawing on examples from the Netherlands Indies, Singapore, Hong Kong, the Philippines, and the Northern Territory of Australia. It explores how photographs of ‘houseboys’ worked as a ‘visual culture’ of empire that was intended to illustrate and immortalize white colonial power, but that also expressed anxieties about colonial projects. As well as a tool for understanding the assertions and insecurities of white colonizers, the article argues that photographs of servants can be used to illuminate the working lives of these Chinese, Malay, Javanese, and Filipino men. Drawing on a remarkable studio portrait that was commissioned by three Filipino servants and an oral history account from a Chinese servant, I conclude that both masters and servants used the photographic medium to assert their power in the home and the colony.
Lonely young adults in modern Britain: findings from an epidemiological cohort study
Authors: Matthews Timothy , Danese Andrea , Caspi Avshalom , Fisher Helen L. , Goldman-Mellor Sidra , Kepa Agnieszka , Moffitt Terrie E. , Odgers Candice L. , Arseneault Louise
Published: April 2018

Background

The aim of this study was to build a detailed, integrative profile of the correlates of young adults’ feelings of loneliness, in terms of their current health and functioning and their childhood experiences and circumstances.

Methods

Data were drawn from the Environmental Risk Longitudinal Twin Study, a birth cohort of 2232 individuals born in England and Wales in 1994 and 1995. Loneliness was measured when participants were aged 18. Regression analyses were used to test concurrent associations between loneliness and health and functioning in young adulthood. Longitudinal analyses were conducted to examine childhood factors associated with young adult loneliness.

Results

Lonelier young adults were more likely to experience mental health problems, to engage in physical health risk behaviours, and to use more negative strategies to cope with stress. They were less confident in their employment prospects and were more likely to be out of work. Lonelier young adults were, as children, more likely to have had mental health difficulties and to have experienced bullying and social isolation. Loneliness was evenly distributed across genders and socioeconomic backgrounds.

Conclusions

Young adults’ experience of loneliness co-occurs with a diverse range of problems, with potential implications for health in later life. The findings underscore the importance of early intervention to prevent lonely young adults from being trapped in loneliness as they age.
Behavior problems in sexually abused preschoolers over a 1-year period: The mediating role of attachment representations
Authors: Charest Florence , Hébert Martine , Bernier Annie , Langevin Rachel , Miljkovitch Raphaële
Published: April 2018

According to the developmental psychopathology framework, adverse childhood experiences, including child sexual abuse (CSA), may alter the course of normal development in children. Attachment security has been identified as a protective factor against psychopathology and may thus play a critical role in predicting victims’ adaptation. The main objective of the present study was to investigate the mediating effect of attachment representations in the relation between CSA and behavior problems over a 1-year period. The sample consisted of 391 children (251 sexually abused) aged 3.5 to 6 years. The Attachment Story Completion Task and the Child Behavior Checklist were used. Disorganized attachment partially mediated the relation between CSA and children's internalizing and externalizing behavior problems 1 year following the initial assessment. This mediation effect was not found for ambivalent nor secure attachment dimensions. Child gender was found to moderate the association between CSA and disorganization, with larger effects of CSA among boys. These findings underscore the importance of considering attachment representations in treatment programs for preschool victims. Evidence-based practice focusing on trauma could be combined with an attachment-based intervention targeting the parent–child relationship. Moreover, interventions should be gender sensitive, as CSA appears to affect boys and girls differently.
Assessing multilingual multimodal image description: Studies of native speaker preferences and translator choices
Authors: FRANK STELLA , ELLIOTT DESMOND , SPECIA LUCIA
Published: April 2018

Two studies on multilingual multimodal image description provide empirical evidence towards two questions at the core of the task: (i) whether target language speakers prefer descriptions generated directly in their native language, as compared to descriptions translated from a different language; (ii) whether images improve human translation of descriptions. These results provide guidance for future work in multimodal natural language processing by first showing that on the whole, translations are not distinguished from native language descriptions, and second delineating and quantifying the information gained from the image during the human translation task.
Where to put the image in an image caption generator
Authors: TANTI MARC , GATT ALBERT , CAMILLERI KENNETH P.
Published: April 2018

When a recurrent neural network (RNN) language model is used for caption generation, the image information can be fed to the neural network either by directly incorporating it in the RNN – conditioning the language model by ‘injecting’ image features – or in a layer following the RNN – conditioning the language model by ‘merging’ image features. While both options are attested in the literature, there is as yet no systematic comparison between the two. In this paper, we empirically show that it is not especially detrimental to performance whether one architecture is used or another. The merge architecture does have practical advantages, as conditioning by merging allows the RNN’s hidden state vector to shrink in size by up to four times. Our results suggest that the visual and linguistic modalities for caption generation need not be jointly encoded by the RNN as that yields large, memory-intensive models with few tangible advantages in performance; rather, the multimodal integration should be delayed to a subsequent stage.
A construction of independent means: the history of theWayconstruction revisited
Authors: FANEGO TERESA
Published: April 2018

The emergence and development of theWayconstruction was famously examined by Israel (1996) in a study which traced the modern form of the construction to three senses or subschemas, namely manner of motion (He stumbled his way to the front door), means of motion (He dug his way out of the prison) and incidental activity (He whistled his way out of the room). The present article moves beyond the late Middle English period – the starting point of Israel's research – and looks at the precursors of theWayconstruction since Old English times, as well as its interaction with the Intransitive Motion construction (IMC) (He walked into the room). By approaching the data in terms of Goldberg's typology (1997) of verb-construction relationships, which is finer-grained than Israel's tripartite division, the analysis identifies the areas of conceptual and constructional overlap that have existed between theWayconstruction and the IMC in the course of history, and shows that theWayconstruction has gradually specialised in the expression of those relations which could not be readily coded in the IMC, such as means of motion and incidental activity. The study thus seeks to contribute to a better understanding of how the constructicon, the repertory of constructions making up the grammar of a language, may change over time.
Effectiveness of a parental school-based intervention to improve young children’s eating patterns: a pilot study
Authors: Gomes Ana Isabel , Barros Luisa , Pereira Ana Isabel , Roberto Magda Sofia
Published: April 2018

Objective

To evaluate the effectiveness of a pilot study of a parental school-based intervention to promote healthy eating behaviours in young children.

Design

A quasi-experimental longitudinal design with three conditions (complete intervention (CIG), minimal intervention (MIG), control (CG)), with repeated measures at baseline, immediately after the intervention, 6 months and 1 year after intervention.

Setting

Fourteen public and state-funded kindergartens near Lisbon, Portugal.

Subjects

Parents (n349) of 3- to 6-year-old children assigned to the three conditions completed the baseline protocol. The ‘Red Apple’ intervention included four parental group sessions about young children’s growth, nutritional guidelines and positive parental feeding strategies, which was combined with adult–child activities at home and in the classroom, and newsletters (CIG). MIG included only a single nutritional counselling session, whereas the CG had no intervention. At the end, thirty-eight, twenty-six and fifty-four parents in the CIG, MIG and CG, respectively, had completed all evaluation components. Data regarding parental perception of children’s weight, self-efficacy, nutritional knowledge, feeding strategies, eating behaviours and BMI were collected at the four assessment moments.

Results

The CIG showed improvements in children’s healthy food intake, compared with the MIG and CG. Parental self-efficacy regarding the regulation of children’s eating behaviours decreased in the CG but not in both intervention groups.

Conclusions

Considering the low dosage of the intervention, the results obtained were positive. Future studies should offer additional solutions to overcome barriers to parents’ participation.
India–Solar Cells: Trade Rules, Climate Policy, and Sustainable Development Goals
Authors: KARTTUNEN MARIANNA , MOORE MICHAEL O.
Published: April 2018

India–Solar Cellsis one of a growing number of WTO disputes that highlight the continuing tensions between climate change polices (and renewable energy manufacturing initiatives in particular) and established multilateral trading rules. The United States alleged that Indian policies discriminated against foreign solar cell suppliers operating in the Indian market. The Appellate Body broadly rejected India's arguments to justify the measure either under Article III.8 public procurement derogations or as a general exception under ‘short supply’ and ‘compliance with laws and regulations’ provision of Article XX of the GATT. We argue that the Appellate Body was correct both on legal and economic grounds. The case does highlight the continuing need for clarity about the allowed parameters for climate change policies within the multilateral trade system.
Russia–Tariff Treatment: Identifying Systematic Violations of WTO Law
Authors: REYNOLDS KARA M. , RIGOD BORIS
Published: April 2018

In October 2014, the European Union requested consultations with Russia under the WTO's dispute settlement system regarding Russia's tariff treatment of various agricultural and manufacturing products. Although most of the measures challenged by the EU were individual tariff lines, the final measure in its complaint was a ‘more general measure’ referred to as the systematic duty variation. A WTO Dispute Panel eventually ruled that the EU failed to establish the systematic nature of the duty treatment afforded by Russia to certain products. In this paper, we explore the Dispute Panel's ruling, as well as how claims of systematic non-compliance are treated in other legal settings. We conclude by exploring whether future WTO Panels should instead consider statistical evidence of systematic treatment to promote compliance.
Split Memory: The Geography of Holocaust Memory and Amnesia in Belarus
Authors: Walke Anika
Published: April 2018

The remote location of Beshankovichy's mass grave for Jewish victims of the Nazi genocide reflects the exclusion of local Jews during the German occupation of Soviet territories and limits their memory to a few knowledgeable survivors and witnesses. In contrast, local commemorative practices focus on memorials for Soviet soldiers, partisans, and their aides. The paper reveals an incongruence of the place of historical experience on the one hand, and the locale of popular commemoration on the other, highlighting the impact of the Holocaust in Belarus to destroy Jewish history and its memory. The spatial division reflects the trauma of loss as much as shame for local participation in the mass murder. Drawing on oral histories, archival materials, and field visits, the study builds on a growing field of scholarship on the role of space and place in the construction of memories and identities in the aftermath of atrocity and trauma to discuss the geographical dimensions of memory and amnesia.
A Discordance Weighting Approach Estimating Occupational and Income Returns to Education
Authors: Andersson Matthew A.
Published: April 2018

Schooling differences between identical twins are often utilized as a natural experiment to estimate returns to education. Despite longstanding doubts about the truly random nature of within-twin-pair schooling discordance, such discordance has not yet been understood comprehensively, in terms of diverse between- and within-family peer, academic, familial, social, and health exposures. Here, a predictive analysis using national U.S. midlife twin data shows that within-pair schooling differences are endogenous to a variety of childhood exposures. Using discordance propensities, returns to education under a true natural experiment are simulated. Results for midlife occupation and income reveal differences in estimated returns to education that are statistically insignificant, suggesting that twin-based estimates of causal effects are robust. Moreover, identical and fraternal twins show similar levels of discordance endogeneity and similar responses to propensity weighting, suggesting that the identical twins may not provide demonstrably better leverage in the causal identification of educational returns.
Coeval Uplift and Subsidence Reveal Magma Recharging Near Rome (Italy)
Authors: Trasatti E. , Marra F. , Polcari M. , Etiope G. , Ciotoli G. , Darrah T. H. , Tedesco D. , Stramondo S. , Florindo F. , Ventura G.
Published: April 2018

Uplift and subsidence alternate throughout the life cycle of a volcano mirroring magma accumulation, migration and/or gas pressurization, and magma cooling or depressurization, respectively. The unusual occurrence of coeval inflation and deflation is difficult to reconcile with the recharging or cooling of a single magma chamber, or hydrological processes. Here we show a persistent flank uplift and central subsidence at Colli Albani volcano near Rome (Italy), by mapping about 20 years of deformation by InSAR data. The magmatic helium signature increases in correspondence with N‐S faults along the western slope of Colli Albani, which are therefore interpreted as deep‐seated structures directly or indirectly connected with an underlying magma reservoir. Deformation modeling shows that these faults are pathways for fresh magma intrusion, whereas a residual magma is cooling below the deflating caldera. Therefore, magma recharge at depth is controlled by major faults along which the vents of the most recent activity (<200 ka ago) concentrate in the western side of the volcano and not by the caldera structures. We demonstrate that the Colli Albani magmatic system is slowly rejuvenating, posing a volcanic threat for Rome.
Numerical Analysis of Hydrofracturing Behaviors and Mechanisms of Heterogeneous Reservoir Glutenite, Using the Continuum‐Based Discrete Element Method While Considering Hydromechanical Coupling and Leak‐Off Effects
Authors: Ju Yang , Chen Jialiang , Wang Yongliang , Gao Feng , Xie Heping
Published: April 2018

Hydrofracturing technology has been widely used to stimulate the tight hydrocarbon reservoirs that usually comprise heterogeneous glutenites. Hydromechanical coupling and leak‐off are essential characteristics of this process and need to be properly addressed in numerical simulation, which plays an important role in quantitatively evaluating the efficiency of this technology. Due to the challenges in accurately representing the complex structure and physical properties of heterogeneous glutenites as well as hydraulic‐driven crack propagation, however, the hydromechanical coupling, leak‐off, and material heterogeneity have not yet been handled satisfactorily. To overcome these challenges, we use the continuum‐based discrete element method (CDEM) to simulate the hydraulic fracturing of heterogeneous glutenites, considering hydromechanical coupling and leak‐off effects. The CDEM models are constructed using the geometrical and physical parameters that were extracted from natural heterogeneous glutenites using computed tomography, X‐ray diffraction, and triaxial tests, based on image processing and reconstruction approaches. The CDEM models are composed of hydraulic fractures and microscale pores, and Darcy's law was integrated within the model to govern fluid leak‐off; this is a nontraditional approach to leak‐off effects. The coupled finite element‐discrete element‐finite volume approach is used to determine the fracturing behaviors of heterogeneous models. The fracturing crack propagation and distribution patterns of homogeneous and heterogeneous models under various horizontal in situ stress differences are characterized by fractal theory, and the models are compared to assess the influences of material heterogeneity and in situ stresses on the hydraulic fracturing of heterogeneous glutenites.
Two Modes of Vertical Velocity in Subsurface Mesoscale Eddies
Authors: Viúdez A.
Published: April 2018

Two fundamental modes of vertical velocity (w) in mesoscale subsurface eddies are described using the quasigeostrophic (QG) approximation and nonhydrostatic numerical modeling. The first mode of w (the spheroidal mode) arises when a spheroidal upright subsurface eddy acquires horizontal eccentricity and becomes an ellipsoid, still upright, vertically symmetric vortex. In this case, the vertical displacement of isopycnals vanishes at the middepth z = 0. Conservation of potential vorticity anomaly (PVA) on elliptical concave/convex isopycnals entails a three‐dimensional octupolar pattern of w which also vanishes at z = 0. The second mode of w (the tilted mode) arises when the eddy remains spheroidal but its vertical axis tilts relative to the vertical direction. In this case, the displacement of isopycnals is largest at the middepth z = 0 and has a dipolar distribution. The associated w is largest at the middepth and develops also a dipolar pattern. In both spheroidal and tilted modes, the vertical velocity pattern may be inferred from the fast advection of PVA conserving fluid particles on slower translating concave/convex or tilted isopycnals. This implies that the vertical velocity of both modes is approximately QG and may be correctly inferred from the QG omega equation as long as the Rossby number remains small. Under more general circumstances, the vortex is both spheroidal and tilted. In this case, both spheroidal and tilted modes coexist but remain, to a large extent, uncoupled, rotating with different and, at least at a first order of approximation, constant phase speeds.
Modeling the Irrigation Withdrawals Over the Coterminous US Using a Hierarchical Modeling Approach
Authors: Das Priyam , Patskoski Jason , Sankarasubramanian A.
Published: April 2018

Studies focusing on national/global water scarcity require water availability and water use to quantify the imbalance. In this regard, annual irrigation withdrawal data reported by the USGS every 5 years provide a valuable information on the water use patterns over the United States. This study develops an empirical model to estimate annual irrigation water withdrawal using irrigated area, climate information, and population as predictors. Given the hierarchy in the data sources, we propose a predictive linear hierarchical regression model to develop annual irrigation water withdrawal models using varying intercepts (VI) and varying intercepts and slopes (VIS) approaches. Estimates from hierarchical models are compared with pooled and unpooled classical regression models. Overall, both hierarchical models outperform the classical models with the adjusted R2 between USGS‐reported and modeled withdrawal estimates being above 0.6 in most states using county and climate division level data. However, due to the spatial difference between the supply (rural areas) and demand (urban areas) for agriculture products, climate division level estimates exhibit a higher adjusted R2 than county level estimates. The VIS model is able to capture local effects better, particularly for states whose irrigation withdrawal patterns significantly differ from the national pattern. The performance of the models is also validated by leaving out the entire nation's water‐use data out (i.e., leave‐one‐out cross‐validation) to ensure the reported skill is not due to overfitting. Split‐sample validation in predicting 2010 irrigation withdrawal also shows the potential of the developed hierarchical model in estimating the annual irrigation withdrawals for the years with no data within the once in 5 year USGS database.
Radial and Azimuthal Anisotropy Tomography of the NE Japan Subduction Zone: Implications for the Pacific Slab and Mantle Wedge Dynamics
Authors: Ishise Motoko , Kawakatsu Hitoshi , Morishige Manabu , Shiomi Katsuhiko
Published: April 2018

We investigate slab and mantle structure of the NE Japan subduction zone from P wave azimuthal and radial anisotropy using travel time tomography. Trench normal E‐W‐trending azimuthal anisotropy (AA) and radial anisotropy (RA) with VPV > VPH are found in the mantle wedge, which supports the existence of small‐scale convection in the mantle wedge with flow‐induced LPO of mantle minerals. In the subducting Pacific slab, trench parallel N‐S‐trending AA and RA with VPH > VPV are obtained. Considering the effect of dip of the subducting slab on apparent anisotropy, we suggest that both characteristics can be explained by the presence of laminar structure, in addition to AA frozen‐in in the subducting plate prior to subduction.
Formation of the Dayside Magnetopause and Its Boundary Layers Under the Radial IMF
Authors: Pi Gilbert , Němeček Zdeněk , Šafránková Jana , Grygorov Kostiantyn , Shue Jih‐Hong
Published: April 2018

The global structure of magnetopause boundary layers under the radial interplanetary magnetic field (IMF) conditions is studied by a comparison of experimental and simulation results. In magnetohydrodynamic simulations, the hemispherical asymmetry of the reconnection locations was found. The draped field adjacent to the magnetopause points northward in the Northern Hemisphere, but it is oriented southward in the Southern Hemisphere at the beginning of the simulation for negative IMF Bx. The magnetopause region affected by the positive IMF Bz component enlarges over time, and the density profile exhibit a north‐south asymmetry near the magnetopause. The experimental part of the study uses the Time History of Events and Macroscale Interactions during Substorm data. We analyze profiles of the plasma parameters and magnetic field as well as the ion pitch‐angle distributions. The nonsimultaneous appearance of parallel and antiparallel aligned flows suggests two spatially separated sources of these flows. We have identified (1) the inner part of the low‐latitude boundary layer (LLBL) on closed magnetic field lines; (2) the outer LLBL on open field lines; (3) the inner part of the magnetosheath boundary layer (MSBL) formed by dayside reconnection in the Southern Hemisphere; and (4) the outer MSBL resulting from lobe reconnection in the Northern Hemisphere.
An Overview of Interactions and Feedbacks Between Ice Sheets and the Earth System
Authors: Fyke Jeremy , Sergienko Olga , Löfverström Marcus , Price Stephen , Lenaerts Jan T. M.
Published: April 2018

Ice sheet response to forced changes—such as that from anthropogenic climate forcing—is closely regulated by two‐way interactions with other components of the Earth system. These interactions encompass the ice sheet response to Earth system forcing, the Earth system response to ice sheet change, and feedbacks resulting from coupled ice sheet/Earth system evolution. Motivated by the impact of Antarctic and Greenland ice sheet change on future sea level rise, here we review the state of knowledge of ice sheet/Earth system interactions and feedbacks. We also describe emerging observation and model‐based methods that can improve understanding of ice sheet/Earth system interactions and feedbacks. We particularly focus on the development of Earth system models that incorporate current understanding of Earth system processes, ice dynamics, and ice sheet/Earth system couplings. Such models will be critical tools for projecting future sea level rise from anthropogenically forced ice sheet mass loss.
Homelessness, Mimesis, and the Flânerie
Authors: Hodgetts Darrin , Stolte Ottilie , Groot Shiloh , Drew Neil
Published: April 2018

As an intense repository for human existence, the contemporary city is textured by scenes of homelessness that manifest broader issues of inequality and poverty in society. This article explores material from photo-elicitation projects with 36 street homeless men in Auckland who were asked to go out into the city and picture their everyday lives. In interpreting the results, we draw on theoretical work on mimesis, urban mobilities, and social practice to conceptualize how homeless people attempt to convey aspects of street life. A core proposition is that in adopting the mobile analytic gaze of flânerie, participants produce photographs as memetic objects that enable them to show and articulate traces of the key places, features, rhythms, practices, and relationships of homelessness.
PGC1α promotes cholangiocarcinoma metastasis by upregulating PDHA1 and MPC1 expression to reverse the Warburg effect
Authors: Dan Li  , Wang Chaoqun , Ma Panfei , Yu Qingan , Gu Mingqi , Dong Liqian , Jiang Wenjing , Pan Shangha , Xie Changming , Han Jihua , Lan Yaliang , Sun Jing , Sheng Ping , Liu Kunpeng , Wu Yaohua , Liu Lianxin , Ma Yong , Jiang Hongchi
Published: April 2018

PGC1α acts as a central regulator of mitochondrial metabolism, whose role in cancer progression has been highlighted but remains largely undefined. Especially, it is completely unknown about the effect of PGC1α on cholangiocarcinoma (CCA). Here we showed that PGC1α overexpression had no impact on CCA growth despite the decreased expression of PGC1α in CCA compared with adjacent normal tissue. Instead, PGC1α overexpression-promoted CCA metastasis both in vitro and in vivo. Mechanistically, for the first time, we illuminated that PGC1α reversed the Warburg effect by upregulating the expression of pyruvate dehydrogenase E1 alpha 1 subunit and mitochondrial pyruvate carrier 1 to increase pyruvate flux into the mitochondria for oxidation, whereas simultaneously promoting mitochondrial biogenesis and fusion to mediate the metabolic switch to oxidative phosphorylation. On the one hand, enhanced mitochondrial oxidation metabolism correlated with elevated reactive oxygen species (ROS) production; on the other hand, increased PGC1α expression upregulated the expression levels of mRNA for several ROS-detoxifying enzymes. To this end, the ROS levels, which were elevated but below a critical threshold, did not inhibit CCA cells proliferation. And the moderately increased ROS facilitated metastatic dissemination of CCA cells, which can be abrogated by antioxidants. Our study suggests the potential utility of developing the PGC1α-targeted therapies or blocking PGC1α signaling axis for inhibiting CCA metastasis.
c-MYC and reactive oxygen species play roles in tetrandrine-induced leukemia differentiation
Authors: Wu Guixian , Liu Ting , Li Han , Li Yafang , Li Dengju , Li Wenhua
Published: April 2018

Tetrandrine is a broadly used bisbenzylisoquinoline alkaloid component of traditional Chinese medicine that has antitumor effects in some cancer types. In this study, we investigated the effects of tetrandrine on leukemia in vitro and in vivo. The results showed that tetrandrine effectively induced differentiation and autophagy in leukemia cells. In addition, tetrandrine treatment activated the accumulation of reactive oxygen species (ROS) and inhibited c-MYC protein expression. Further, we found that treatment with the ROS scavengers N-acetyl-L-cysteine (NAC) and Tiron as well as overexpression of c-MYC reduced tetrandrine-induced autophagy and differentiation. Moreover, a small molecular c-MYC inhibitor, 10058-F4, enhanced the tetrandrine-induced differentiation of leukemia cells. These results suggest that ROS generation and c-MYC suppression play important roles in tetrandrine-induced autophagy and differentiation, and the results from in vivo experiments were consistent with those from in vitro studies. Therefore, our data suggest that tetrandrine may be a promising agent for the treatment of leukemia.
The therapeutic effect of miR-125b is enhanced by the prostaglandin endoperoxide synthase 2/cyclooxygenase 2 blockade and hampers ETS1 in the context of the microenvironment of bone metastasis
Authors: Maroni Paola , Bendinelli Paola , Matteucci Emanuela , Desiderio Maria Alfonsina
Published: April 2018

Bone is the most common site for breast cancer spread. In the pro-metastatic cell line 1833, derived from MDA-MB-231 breast adenocarcinoma cells, both hypoxia and hepatocyte growth factor (HGF) influence the effect of miR-125b on ETS proto-oncogene 1 transcription factor (ETS1). The effect of hypoxia inducible factor 1 alpha subunit (HIF1A), known to promote metastatic spread by upregulating prostaglandin endoperoxide synthase 2 (PTGS2), may be dampened by miR-125b targeting PTGS2. Here, we investigated whether miR-125b plays a role in breast cancer metastasis by measuring its activity in response to the chemotherapeutic agent NS-398 in a xenograft model. NS-398 is typically used in the clinic to target PTGS2. We also aimed to describe the molecular mechanisms in vitro, since the enhancement of epithelial properties may favor the efficacy of therapies. We report that in the xenograft model, miR-125b reduced metastasis to the bone. We also report suppression of PTGS2 enhanced survival by decreasing HIF1A in cells within the bone marrow. In 1833 cells transfected with a miR-125b mimic we observed several phenotypic changes including enhancement of the epithelial marker E-cadherin, a reduction of mesenchymal-associated genes and a reduction of WNT-associated stem cell signaling. Our findings suggest that in vivo, key players of the bone microenvironment promoting breast cancer spread are regulated by miR-125b. In future, biological molecules imitating miR-125b may enhance the sensitivity of chemotherapeutic agents used to counteract bone metastases.
YAP1 contributes to NSCLC invasion and migration by promoting Slug transcription via the transcription co-factor TEAD
Authors: Yu Mengxue , Chen Yingzhun , Li Xuelian , Yang Rui , Zhang Lijia , Huangfu Longtao , Zheng Nan , Zhao Xiaoguang , Lv Lifang , Hong Yaozhen , Liang Haihai , Shan Hongli
Published: April 2018

Yes-associated protein 1 (YAP1) contributes to the development of multiple tumors, but the mechanism underlying YAP1 deregulation in non-small cell lung cancer (NSCLC) remains unclear. By performing immunohistochemistry (IHC) assays, we found that YAP1 was significantly upregulated in NSCLC compared with adjacent tissues; therefore, we sought to elucidate whether the upregulation of YAP1 contributes to NSCLC progression. MTT and transwell assays showed that YAP1 overexpression promoted proliferation, migration, and invasion in the NSCLC cell lines A549 and H460; YAP1 overexpression also promoted the significant differential expression of epithelial-mesenchymal transition (EMT)-related markers. Nevertheless, YAP1 knockdown alleviated TGF-β1-induced EMT and proliferation, migration, and invasion in NSCLC. Furthermore, western blotting showed that the co-transcription complex YAP1/TEAD was impaired by YAPS94A (a YAP1 mutant without the TEAD binding site), and verteporfin (a small molecular inhibitor of YAP1) inhibited A549 and H460 cell metastasis and EMT-related markers expression, indicating that TEAD mediated the NSCLC aggressiveness induced by YAP1. Moreover, sequence analysis and ChIP and luciferase assays confirmed that YAP1 transcriptionally activated Slug expression by binding to TEAD. Importantly, silencing YAP1 inhibited A549 cell tumorigenesis and EMT and downregulated Slug expression in vivo. Overall, our findings revealed that YAP1 is a driver of NSCLC metastasis because YAP1 promoted the EMT program by inducing Slug transcription.
Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome
Authors: Balmus Gabriel , Larrieu Delphine , Barros Ana C. , Collins Casey , Abrudan Monica , Demir Mukerrem , Geisler Nicola J. , Lelliott Christopher J. , White Jacqueline K. , Karp Natasha A. , Atkinson James , Kirton Andrea , Jacobsen Matt , Clift Dean , Rodriguez Raphael ,   Sanger Mouse Genetics Project, Shannon Carl , Sanderson Mark , Gates Amy , Dench Joshua , Vancollie Valerie , McCarthy Catherine , Pearson Selina , Cambridge Emma , Isherwood Christopher , Wilson Heather , Grau Evelyn , Galli Antonella , Hooks Yvette E. , Tudor Catherine L. , Green Angela L. , Kussy Fiona L. , Tuck Elizabeth J. , Siragher Emma J. , McLaren Robbie S. B. , Swiatkowska Agnieszka , Caetano Susana S. , Mazzeo Cecilia Icoresi , Dabrowska Monika H. , Maguire Simon A. , Lafont David T. , Anthony Lauren F. E. , Sumowski Maksymilian T. , Bussell James , Sinclair Caroline , Brown Ellen , Doe Brendan , Wardle-Jones Hannah , Griggs Nicola , Woods Mike , Kundi Helen , McConnell George , Doran Joanne , Griffiths Mark N. D. , Kipp Christian , Holroyd Simon A. , Gannon David J. , Alcantara Rafael , Ramirez–Solis Ramiro , Bottomley Joanna , Ingle Catherine , Ross Victoria , Barrett Daniel , Sethi Debarati , Gleeson Diane , Burvill Jonathan , Platte Radka , Ryder Edward , Sins Elodie , Miklejewska Evelina , Von Schiller Dominique , Duddy Graham , Urbanova Jana , Boroviak Katharina , Imran Maria , Reddy Shalini Kamu , Adams David J. , Jackson Stephen P.
Published: April 2018

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare, but devastating genetic disease characterized by segmental premature aging, with cardiovascular disease being the main cause of death. Cells from HGPS patients accumulate progerin, a permanently farnesylated, toxic form of Lamin A, disrupting the nuclear shape and chromatin organization, leading to DNA-damage accumulation and senescence. Therapeutic approaches targeting farnesylation or aiming to reduce progerin levels have provided only partial health improvements. Recently, we identified Remodelin, a small-molecule agent that leads to amelioration of HGPS cellular defects through inhibition of the enzyme N-acetyltransferase 10 (NAT10). Here, we show the preclinical data demonstrating that targeting NAT10 in vivo, either via chemical inhibition or genetic depletion, significantly enhances the healthspan in a Lmna
G609G
HGPS mouse model. Collectively, the data provided here highlights NAT10 as a potential therapeutic target for HGPS.
Transporter gene acquisition and innovation in the evolution of Microsporidia intracellular parasites
Authors: Dean P. , Sendra K. M. , Williams T. A. , Watson A. K. , Major P. , Nakjang S. , Kozhevnikova E. , Goldberg A. V. , Kunji E. R. S. , Hirt R. P. , Embley T. M.
Published: April 2018

The acquisition of genes by horizontal transfer can impart entirely new biological functions and provide an important route to major evolutionary innovation. Here we have used ancient gene reconstruction and functional assays to investigate the impact of a single horizontally transferred nucleotide transporter into the common ancestor of the Microsporidia, a major radiation of intracellular parasites of animals and humans. We show that this transporter provided early microsporidians with the ability to steal host ATP and to become energy parasites. Gene duplication enabled the diversification of nucleotide transporter function to transport new substrates, including GTP and NAD+, and to evolve the proton-energized net import of nucleotides for nucleic acid biosynthesis, growth and replication. These innovations have allowed the loss of pathways for mitochondrial and cytosolic energy generation and nucleotide biosynthesis that are otherwise essential for free-living eukaryotes, resulting in the highly unusual and reduced cells and genomes of contemporary Microsporidia.
A photochemical diode artificial photosynthesis system for unassisted high efficiency overall pure water splitting
Authors: Chowdhury Faqrul A. , Trudeau Michel L. , Guo Hong , Mi Zetian
Published: April 2018

The conversion of solar energy into chemical fuels can potentially address many of the energy and environment related challenges we face today. In this study, we have demonstrated a photochemical diode artificial photosynthesis system that can enable efficient, unassisted overall pure water splitting without using any sacrificial reagent. By precisely controlling charge carrier flow at the nanoscale, the wafer-level photochemical diode arrays exhibited solar-to-hydrogen efficiency ~3.3% in neutral (pH ~ 7.0) overall water splitting reaction. In part of the visible spectrum (400–485 nm), the energy conversion efficiency and apparent quantum yield reaches ~8.75% and ~20%, respectively, which are the highest values ever reported for one-step visible-light driven photocatalytic overall pure water splitting. The effective manipulation and control of charge carrier flow in nanostructured photocatalysts provides critical insight in achieving high efficiency artificial photosynthesis, including the efficient and selective reduction of CO2 to hydrocarbon fuels.
An enrichment method based on synergistic and reversible covalent interactions for large-scale analysis of glycoproteins
Authors: Xiao Haopeng , Chen Weixuan , Smeekens Johanna M. , Wu Ronghu
Published: April 2018

Protein glycosylation is ubiquitous in biological systems and essential for cell survival. However, the heterogeneity of glycans and the low abundance of many glycoproteins complicate their global analysis. Chemical methods based on reversible covalent interactions between boronic acid and glycans have great potential to enrich glycopeptides, but the binding affinity is typically not strong enough to capture low-abundance species. Here, we develop a strategy using dendrimer-conjugated benzoboroxole to enhance the glycopeptide enrichment. We test the performance of several boronic acid derivatives, showing that benzoboroxole markedly increases glycopeptide coverage from human cell lysates. The enrichment is further improved by conjugating benzoboroxole to a dendrimer, which enables synergistic benzoboroxole–glycan interactions. This robust and simple method is highly effective for sensitive glycoproteomics analysis, especially capturing low-abundance glycopeptides. Importantly, the enriched glycopeptides remain intact, making the current method compatible with mass-spectrometry-based approaches to identify glycosylation sites and glycan structures.
The genetic architecture of floral traits in the woody plant Prunus mume
Authors: Zhang Qixiang , Zhang He , Sun Lidan , Fan Guangyi , Ye Meixia , Jiang Libo , Liu Xin , Ma Kaifeng , Shi Chengcheng , Bao Fei , Guan Rui , Han Yu , Fu Yuanyuan , Pan Huitang , Chen Zhaozhe , Li Liangwei , Wang Jia , Lv Meiqi , Zheng Tangchun , Yuan Cunquan , Zhou Yuzhen , Lee Simon Ming-Yuen , Yan Xiaolan , Xu Xun , Wu Rongling , Chen Wenbin , Cheng Tangren
Published: April 2018

Mei (Prunus mume) is an ornamental woody plant that has been domesticated in East Asia for thousands of years. High diversity in floral traits, along with its recent genome sequence, makes mei an ideal model system for studying the evolution of woody plants. Here, we investigate the genetic architecture of floral traits in mei and its domestication history by sampling and resequencing a total of 351 samples including 348 mei accessions and three other Prunus species at an average sequencing depth of 19.3×. Highly-admixed population structure and introgression from Prunus species are identified in mei accessions. Through a genome-wide association study (GWAS), we identify significant quantitative traits locus (QTLs) and genomic regions where several genes, such as MYB108, are positively associated with petal color, stigma color, calyx color, and bud color. Results from this study shed light on the genetic basis of domestication in flowering plants, particularly woody plants.
Manipulation of insulin signaling phenocopies evolution of a host-associated polyphenism
Authors: Fawcett Meghan M. , Parks Mary C. , Tibbetts Alice E. , Swart Jane S. , Richards Elizabeth M. , Vanegas Juan Camilo , Cenzer Meredith , Crowley Laura , Simmons William R. , Hou Wenzhen Stacey , Angelini David R.
Published: April 2018

Plasticity, the capacity of an organism to respond to its environment, is thought to evolve through changes in development altering the integration of environmental cues. In polyphenism, a discontinuous plastic response produces two or more phenotypic morphs. Here we describe evolutionary change in wing polyphenism and its underlying developmental regulation in natural populations of the red-shouldered soapberry bug, Jadera haematoloma (Insecta: Hemiptera: Rhopalidae) that have adapted to a novel host plant. We find differences in the fecundity of morphs in both sexes and in adult expression of insulin signaling components in the gonads. Further, the plastic response of ancestral-state bugs can be shifted to resemble the reaction norm of derived bugs by the introduction of exogenous insulin or RNA interference targeting the insulin signaling component encoded by FoxO. These results suggest that insulin signaling may be one pathway involved in the evolution of this polyphenism, allowing adaptation to a novel nutritional environment.
Non-contact identification and differentiation of illicit drugs using fluorescent films
Authors: Liu Ke , Shang Congdi , Wang Zhaolong , Qi Yanyu , Miao Rong , Liu Kaiqiang , Liu Taihong , Fang Yu
Published: April 2018

Sensitive and rapid identification of illicit drugs in a non-contact mode remains a challenge for years. Here we report three film-based fluorescent sensors showing unprecedented sensitivity, selectivity, and response speed to the existence of six widely abused illicit drugs, including methamphetamine (MAPA), ecstasy, magu, caffeine, phenobarbital (PB), and ketamine in vapor phase. Importantly, for these drugs, the sensing can be successfully performed after 5.0 × 105, 4.0 × 105, 2.0 × 105, 1.0 × 105, 4.0 × 104, and 2.0 × 102 times dilution of their saturated vapor with air at room temperature, respectively. Also, presence of odorous substances (toiletries, fruits, dirty clothes, etc.), water, and amido-bond-containing organic compounds (typical organic amines, legal drugs, and different amino acids) shows little effect upon the sensing. More importantly, discrimination and identification of them can be realized by using the sensors in an array way. Based upon the discoveries, a conceptual, two-sensor based detector is developed, and non-contact detection of the drugs is realized.
Author Correction: Evidence for deficient motor planning in ADHD
Authors: Dahan Anat , Reiner Miriam
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
The signalling game between plants and pollinators
Authors: Sun Shan , Leshowitz Michael I. , Rychtář Jan
Published: April 2018

Plants can send floral signals to advertise their reward for pollinators. Based on the presence or absents of such signals, pollinators can determine whether to visit plants. Plants can send dishonest signals but foraging behaviours of pollinators can limit the cheating strategies of plants. We model the plant-pollinator interactions by the two-type Spence signalling game and investigate the conditions under which honest signalling can be established. In our model, plants either send costly signal or they do not. The cost of signal is dependent on the quality of plant. Pollinators can learn from the interactions with plants and can update their willingness to visit plants’ flowers to maximize their foraging efficiency. We find three general conditions that are required for the evolutionary stability of honest signaling. Those conditions are satisfied if there is (a) a high frequency of high-yield signalling plants in the population, (b) the balance between cost and benefit of signalling, and (c) high cost of dishonest signalling. Our model also predicts that other factors contributing to the establishment of honest signaling are the low abundance of pollinators, and the positive density-dependent and positive frequency-dependent relationship between plants and pollinators.