bluuebunny/crossref_metadata_2025 huggingface dataset:
Presence of the snow leopard Panthera uncia confirmed at four sites in the Chinese Tianshan Mountains
Authors: Buzzard Paul J. , MaMing Roller , Turghan Mardan , Xiong Jiawu , Zhang Tong
Published: July 2017

The Endangered snow leopard Panthera uncia is a flagship species of mountainous central Asia, and a conservation concern. China has the largest extent of potential snow leopard habitat and is thus crucial for snow leopard conservation. There are many challenges to snow leopard conservation in China, however, and there is still little information on the species for many geographical locations, including the Tianshan Mountains of Xinjiang province, which are important because they potentially connect snow leopard populations in Krygyzstan and Kazakhstan with those in Mongolia. We used camera traps in four areas across eastern, central and western Tianshan, with a total survey effort of 3,216 camera-trapping days. We confirmed the presence of snow leopards and an abundance of potential snow leopard prey, including the Siberian ibex Capra sibirica, in all areas. We found 2–3 individual adult snow leopards at each site, with relatively limited survey effort, and more study is needed to fully investigate the importance of the Tianshan Mountains for the species. Establishing more protected areas is essential for snow leopard conservation, and we have used data from this study to apply for protected area status for several areas.
DRUG DISINVESTMENT FRAMEWORKS: COMPONENTS, CHALLENGES, AND SOLUTIONS
Authors: Maloney Mary Alison , Schwartz Lisa , O'Reilly Daria , Levine Mitchel
Published: July 2017

Objectives:Value assessments of marketed drug technologies have been developed through disinvestment frameworks. Components of these frameworks are varied and implementation challenges are prevalent. The objective of this systematic literature review was to describe disinvestment framework process components for drugs and to report on framework components, challenges, and solutions.

Methods:A systematic literature search was conducted using the terms: reassessment, reallocation, reinvestment, disinvestment, delist, decommission or obsolescence in MEDLINE, EMBASE, NLM PubMed, the Cochrane Library, and CINAHL from January 1, 2000, until November 14, 2015. Additional citations were identified through a gray literature search of Health Technology Assessment international (HTAi) and the International Network of Agencies for Health Technology Assessment (INAHTA) member Web sites and from bibliographies of full-text reviewed manuscripts.

Results:Sixty-three articles underwent full text review and forty were included in the qualitative analysis. Framework components including disinvestment terms and definitions, identification and prioritization criteria and methods, assessment processes, stakeholders and dissemination strategies, challenges, and solutions were compiled. This review finds that stakeholders lack the political, administrative, and clinical will to support disinvestment and that there is not one disinvestment framework that is considered best practice.

Conclusions:Drug technology disinvestment components and processes vary and challenges are numerous. Future research should focus on lessening value assessment challenges. This could include adopting more neutral framework terminology, setting fixed reassessment timelines, conducting therapeutic reviews, and modifying current qualitative decision-making assessment frameworks.
SEMANTIC AND STRUCTURAL TASKS FOR THE MAPPING COMPONENT OF L2 VOCABULARY LEARNING
Authors: Kida Shusaku , Barcroft Joe
Published: July 2017

The type of processing–resource allocation (TOPRA) model predicts that increasing one type of processing (semantic, structural, or mapping oriented) can decrease other types of processing and their learning counterparts. This study examined how semantic and structural tasks affect the mapping component of second language (L2) vocabulary learning. Japanese-speaking L2 English learners attempted to map secondary meanings of 24 English homographs. Each participant studied them (a) while making pleasantness ratings about word meaning (mapping plus semantic processing); (b) while counting letters in each word (mapping plus structural processing); and (c) without any additional task (mapping only). Results of L1 (first language) and L2 free recalls and L2-to-L1 and L1-to-L2 cued recalls indicated higher free recall in the semantic condition over the structural condition and higher cued recall in the mapping condition over the semantic and structural conditions, providing qualitatively new evidence for TOPRA model predictions.
Contribution of ultra-processed foods in the diet of adults from the French NutriNet-Santé study
Authors: Julia Chantal , Martinez Lucien , Allès Benjamin , Touvier Mathilde , Hercberg Serge , Méjean Caroline , Kesse-Guyot Emmanuelle
Published: July 2017

Objective

Concerns have been raised about the potential health impact of ultra-processed foods (UPF) in the diet. Our objective was to investigate the contribution of UPF in the diet in a large French population and its association with sociodemographic factors and dietary patterns.

Design

Cross-sectional analysis of dietary data from 74 470 participants in the web-based NutriNet-Santé cohort. UPF were identified in repeated 24 h records and the proportion (in weight) of UPF in the total diet (UPFp) was computed for each participant. Associations of sociodemographic characteristics and UPFp in quartiles were assessed using multivariate multinomial logistic regression. Food group consumption and nutrient intakes across quartiles of UPFp were estimated using linear regression adjusted for sociodemographic factors and energy intake.

Setting

France.

Results

UPF contributed 18·4 % of the foods consumed in weight and 35·9 % of total energy intake. Higher UPFp consumption was independently associated with male gender, younger age, lower education, smoking, and overweight and obesity (all P<0·0001). Participants in the highest UPFp quartile consumed lower amounts of fruit and vegetables (difference between quartile 4 and quartile 1 of UPFp, Δ=−180·3 g/d) and higher amounts of sweet products (Δ=68·5 g/d) and soft drinks (Δ=98·6 g/d; all P<0·0001). They had higher intakes of energy (Δ=610 kJ/d (145·7 kcal/d)) and added sugar (Δ=17·1 g/d), and lower intakes of fibre (Δ=−4·04 g/d), β-carotene (Δ=−1019·6 μg/d) and Ca (Δ=−87·8 mg/d; all P<0·0001).

Conclusions

UPF represent an important part of the diet in adults from the French general population and are associated with unbalanced nutritional intakes.
Parental coping in the context of having a child who is facing death: A theoretical framework
Authors: Darlington Anne-Sophie E. , Korones David N. , Norton Sally A.
Published: July 2017

Objective:

While improvements in healthcare have resulted in children with complex and life-threatening conditions living longer, a proportion of them still die. The death of a child puts parents at increased risk for anxiety, depression, and complicated grief. Increasing our understanding of the coping strategies that parents use under such extreme circumstances will enable us to best provide support to families, before and after a child's death. Our aim herein was to develop a theoretical framework of parental coping.

Method:

Evidence from the literature was employed to develop a theoretical framework to describe parental coping in the context of having a child with a life-limiting illness who is declining and facing eventual death.

Results:

The reasoning and argument consists of three guiding elements: (1) the importance of approach as well as avoidance (as coping strategies) in the context of managing the extreme emotions; (2) the importance of the social aspect of coping within a family, whereby parents cope for others as well as for themselves; and (3) the importance of a flexible and balanced coping profile, with parents using different coping strategies simultaneously. Central to the proposed framework is that effective coping, in terms of adjustment, is achieved by balancing coping strategies: accessing different coping strategies simultaneously or in parallel with a specific focus on (1) approach and avoidance and (2) coping aimed at self and others.

Significance of results:

Understanding of parental coping strategies is essential for health professionals in order to support parents effectively.
Disturbance features, coordination and cooperation: an institutional economics analysis of adaptations in the Spanish irrigation sector
Authors: VILLAMAYOR-TOMAS SERGIO
Published: July 2017

This paper explores associations between disturbances and cooperative responses in a selection of irrigation associations from Spain. Transaction costs and collective action theories are used to characterize disturbances and responses. Disturbances are characterized by looking at the uncertainty they generate, their frequency, the distance of the transacting partners they affect, and their impact on asset-specific transactions. Responses are assessed based on the collective action tasks they involve and classified into coordination and cooperation responses. A qualitative comparative analysis confirms two pathways that are sufficient for the emergence of cooperation responses. The first path is congruent with transaction costs theory, and points to disturbances that are frequent and asset specific; the second path supports relational theory, and points to disturbances that emerge progressively from within the system. Other patterns include the tendency of irrigation associations to delegate to external entities when disturbances are external and occur frequently; and the adaptation of existing institutions when the disturbances are internal and progressive.
p75NTR antagonists attenuate photoreceptor cell loss in murine models of retinitis pigmentosa
Authors: Platón-Corchado María , Barcelona Pablo F , Jmaeff Sean , Marchena Miguel , Hernández-Pinto Alberto M , Hernández-Sánchez Catalina , Saragovi H Uri , de la Rosa Enrique J
Published: July 2017

ProNGF signaling through p75NTR has been associated with neurodegenerative disorders. Retinitis pigmentosa (RP) comprises a group of inherited retinal dystrophies that causes progressive photoreceptor cell degeneration and death, at a rate dependent on the genetic mutation. There are more than 300 mutations causing RP, and this is a challenge to therapy. Our study was designed to explore a common mechanism for p75NTR in the progression of RP, and assess its potential value as a therapeutic target. The proNGF/p75NTR system is present in the dystrophic retina of the rd10 RP mouse model. Compared with wild-type (WT) retina, the levels of unprocessed proNGF were increased in the rd10 retina at early degenerative stages, before the peak of photoreceptor cell death. Conversely, processed NGF levels were similar in rd10 and WT retinas. ProNGF remained elevated throughout the period of photoreceptor cell loss, correlating with increased expression of α2-macroglobulin, an inhibitor of proNGF processing. The neuroprotective effect of blocking p75NTR was assessed in organotypic retinal cultures from rd10 and RhoP mouse models. Retinal explants treated with p75NTR antagonists showed significantly reduced photoreceptor cell death, as determined by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and by preservation of the thickness of the outer nuclear layer (ONL), where photoreceptor nuclei are located. This effect was accompanied by decreased retinal-reactive gliosis and reduced TNFα secretion. Use of p75NTR antagonist THX-B (1,3-diisopropyl-1-[2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-acetyl]-urea) in vivo in the rd10 and RhoP mouse models, by a single intravitreal or subconjunctival injection, afforded neuroprotection to photoreceptor cells, with preservation of the ONL. This study demonstrates a role of the p75NTR/proNGF axis in the progression of RP, and validates these proteins as therapeutic targets in two different RP models, suggesting utility irrespective of etiology.
Killing two birds with one stone: dual blockade of integrin and FGF signaling through targeting syndecan-4 in postoperative capsular opacification
Authors: Qin Yingyan , Zhu Yi , Luo Furong , Chen Chuan , Chen Xiaoyun , Wu Mingxing
Published: July 2017

The most common complication after cataract surgery is postoperative capsular opacification, which includes anterior capsular opacification (ACO) and posterior capsular opacification (PCO). Increased adhesion of lens epithelial cells (LECs) to the intraocular lens material surface promotes ACO formation, whereas proliferation and migration of LECs to the posterior capsule lead to the development of PCO. Cell adhesion is mainly mediated by the binding of integrin to extracellular matrix proteins, while cell proliferation and migration are regulated by fibroblast growth factor (FGF). Syndecan-4 (SDC-4) is a co-receptor for both integrin and FGF signaling pathways. Therefore, SDC-4 may be an ideal therapeutic target for the prevention and treatment of postoperative capsular opacification. However, how SDC-4 contributes to FGF-mediated proliferation, migration, and integrin-mediated adhesion of LECs is unclear. Here, we found that downregulation of SDC-4 inhibited FGF signaling through the blockade of ERK1/2 and PI3K/Akt/mTOR activation, thus suppressing cell proliferation and migration. In addition, downregulation of SDC-4 suppressed integrin-mediated cell adhesion through inhibiting focal adhesion kinase (FAK) phosphorylation. Moreover, SDC-4 knockout mice exhibited normal lens morphology, but had significantly reduced capsular opacification after injury. Finally, SDC-4 expression level was increased in the anterior capsule LECs of age-related cataract patients. Taken together, we for the first time characterized the key regulatory role of SDC-4 in FGF and integrin signaling in human LECs, and provided the basis for future pharmacological interventions of capsular opacification.
Aryl hydrocarbon receptor activation restores filaggrin expression via OVOL1 in atopic dermatitis
Authors: Tsuji Gaku , Hashimoto-Hachiya Akiko , Kiyomatsu-Oda Mari , Takemura Masaki , Ohno Fumitaka , Ito Takamichi , Morino-Koga Saori , Mitoma Chikage , Nakahara Takeshi , Uchi Hiroshi , Furue Masutaka
Published: July 2017

Filaggrin (FLG) mutation is a well-confirmed genetic aberration in atopic dermatitis (AD). Genome-wide association studies on AD have revealed other susceptibility genes, for example, Ovo-like 1 (OVOL1). Nonetheless, the relation between FLG and OVOL1 is unclear. Because aryl hydrocarbon receptor (AHR; a ligand-activated transcription factor), plays a role in FLG expression in keratinocytes, we hypothesized that AHR regulates FLG expression via OVOL1. To demonstrate this mechanism, we analyzed FLG expression in OVOL1-overexpressing or OVOL1-knockdown normal human epidermal keratinocytes (NHEKs). Furthermore, we tested whether AHR activation by 6-formylindolo(3,2-b)carbazole (FICZ), an endogenous AHR ligand, or Glyteer, clinically used soybean tar, upregulates FLG and OVOL1 expression in NHEKs. We found that (1) OVOL1 regulates FLG expression; (2) AHR activation upregulates OVOL1; and (3) AHR activation upregulates FLG via OVOL1. Moreover, nuclear translocation of OVOL1 was less pronounced in AD skin compared with normal skin. IL-4-treated NHEKs, an in vitro AD skin model, also showed inhibition of the OVOL1 nuclear translocation, which was restored by FICZ and Glyteer. Thus, targeting the AHR–OVOL1–FLG axis may provide new therapeutics for AD.
BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4 via interaction with its transcript
Authors: Liu Bao-Qin , Zhang Song , Li Si , An Ming-Xin , Li Chao , Yan Jing , Wang Jia-Mei , Wang Hua-Qin
Published: July 2017

BAG3 is an evolutionarily conserved co-chaperone expressed at high levels and has a prosurvival role in many tumor types. The current study reported that BAG3 was induced under specific floating culture conditions that enrich breast cancer stem cell (BCSC)-like cells in spheres. Ectopic BAG3 overexpression increased CD44+/CD24− CSC subpopulations, first-generation and second-generation mammosphere formation, indicating that BAG3 promotes CSC self-renewal and maintenance in breast cancer. We further demonstrated that mechanically, BAG3 upregulated CXCR4 expression at the post-transcriptional level. Further studies showed that BAG3 interacted with CXCR4 mRNA and promoted its expression via its coding and 3′-untranslational regions. BAG3 was also found to be positively correlated with CXCR4 expression and unfavorable prognosis in patients with breast cancer. Taken together, our data demonstrate that BAG3 promotes BCSC-like phenotype through CXCR4 via interaction with its transcript. Therefore, this study establishes BAG3 as a potential adverse prognostic factor and a therapeutic target of breast cancer.
Amoeba-like self-oscillating polymeric fluids with autonomous sol-gel transition
Authors: Onoda Michika , Ueki Takeshi , Tamate Ryota , Shibayama Mitsuhiro , Yoshida Ryo
Published: July 2017

In the field of polymer science, many kinds of polymeric material systems that show a sol-gel transition have been created. However, most systems are unidirectional stimuli-responsive systems that require physical signals such as a change in temperature. Here, we report on the design of a block copolymer solution that undergoes autonomous and periodic sol-gel transition under constant conditions without any on–off switching through external stimuli. The amplitude of this self-oscillation of the viscosity is about 2,000 mPa s. We also demonstrate an intermittent forward motion of a droplet of the polymer solution synchronized with the autonomous sol-gel transition. This polymer solution bears the potential to become the base for a type of slime-like soft robot that can transform its shape kaleidoscopically and move autonomously, which is associated with the living amoeba that moves forward by a repeated sol-gel transition.
Manipulation of nuclear architecture through CRISPR-mediated chromosomal looping
Authors: Morgan Stefanie L. , Mariano Natasha C. , Bermudez Abel , Arruda Nicole L. , Wu Fangting , Luo Yunhai , Shankar Gautam , Jia Lin , Chen Huiling , Hu Ji-Fan , Hoffman Andrew R. , Huang Chiao-Chain , Pitteri Sharon J. , Wang Kevin C.
Published: July 2017

Chromatin looping is key to gene regulation, yet no broadly applicable methods to selectively modify chromatin loops have been described. We have engineered a method for chromatin loop reorganization using CRISPR-dCas9 (CLOuD9) to selectively and reversibly establish chromatin loops. We demonstrate the power of this technology to selectively modulate gene expression at targeted loci.
Radiocarbon constraints on the glacial ocean circulation and its impact on atmospheric CO2
Authors: Skinner L. C. , Primeau F. , Freeman E. , de la Fuente M. , Goodwin P. A. , Gottschalk J. , Huang E. , McCave I. N. , Noble T. L. , Scrivner A. E.
Published: July 2017

While the ocean’s large-scale overturning circulation is thought to have been significantly different under the climatic conditions of the Last Glacial Maximum (LGM), the exact nature of the glacial circulation and its implications for global carbon cycling continue to be debated. Here we use a global array of ocean–atmosphere radiocarbon disequilibrium estimates to demonstrate a ∼689±53 14C-yr increase in the average residence time of carbon in the deep ocean at the LGM. A predominantly southern-sourced abyssal overturning limb that was more isolated from its shallower northern counterparts is interpreted to have extended from the Southern Ocean, producing a widespread radiocarbon age maximum at mid-depths and depriving the deep ocean of a fast escape route for accumulating respired carbon. While the exact magnitude of the resulting carbon cycle impacts remains to be confirmed, the radiocarbon data suggest an increase in the efficiency of the biological carbon pump that could have accounted for as much as half of the glacial–interglacial CO2 change.
Early-life disruption of amphibian microbiota decreases later-life resistance to parasites
Authors: Knutie Sarah A. , Wilkinson Christina L. , Kohl Kevin D. , Rohr Jason R.
Published: July 2017

Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.
Diffusive, Displacive Deformations and Local Phase Transformation Govern the Mechanics of Layered Crystals: The Case Study of Tobermorite
Authors: Tao Lei , Shahsavari Rouzbeh
Published: July 2017

Understanding the deformation mechanisms underlying the mechanical behavior of materials is the key to fundamental and engineering advances in materials' performance. Herein, we focus on crystalline calcium-silicate-hydrates (C-S-H) as a model system with applications in cementitious materials, bone-tissue engineering, drug delivery and refractory materials, and use molecular dynamics simulation to investigate its loading geometry dependent mechanical properties. By comparing various conventional (e.g. shear, compression and tension) and nano-indentation loading geometries, our findings demonstrate that the former loading leads to size-independent mechanical properties while the latter results in size-dependent mechanical properties at the nanometer scales. We found three key mechanisms govern the deformation and thus mechanics of the layered C-S-H: diffusive-controlled and displacive-controlled deformation mechanisms, and strain gradient with local phase transformations. Together, these elaborately classified mechanisms provide deep fundamental understanding and new insights on the relationship between the macro-scale mechanical properties and underlying molecular deformations, providing new opportunities to control and tune the mechanics of layered crystals and other complex materials such as glassy C-S-H, natural composite structures, and manmade laminated structures.
Neuron-autonomous transcriptome changes upon ischemia/reperfusion injury
Authors: Shi Jinlong , Chen Xia , Li Haiying , Wu Youjia , Wang Shouyan , Shi Wei , Chen Jian , Ni Yaohui
Published: July 2017

Ischemic stroke and the following reperfusion, an acute therapeutic intervention, can cause irreversible brain damages. However, the underlying pathological mechanisms are still under investigation. To obtain a comprehensive, real-time view of the cell-autonomous mechanisms involved in ischemic stroke and reperfusion, we applied the next-generation sequencing (NGS) technology to characterize the temporal changes in gene expression profiles using primarily cultured hippocampal neurons under an oxygen-glucose deprivation/reperfusion (OGD/R) condition. We first identified the differentially expressed genes (DEGs) between normal cultured neurons, neurons with OGD, and neurons with OGD followed by reperfusion for 6 h, 12 h, and 18 h, respectively. We then performed bioinformatics analyses, including gene ontological (GO) and pathway analysis and co-expression network analysis to screen for novel key pathways and genes involved in the pathology of OGD/R. After we confirmed the changes of selected key genes in hippocampal cultures with OGD/R, we further validated their expression changes in an in vivo ischemic stroke model (MCAO). Finally, we demonstrated that prevention of the up-regulation of a key gene (Itga5) associated with OGD/R promoted hippocampal neuronal survival. Our research thereby provided novel insights into the molecular mechanisms in ischemic stroke pathophysiology and potential targets for therapeutic intervention after ischemic stroke.
Midnolin is a novel regulator of parkin expression and is associated with Parkinson’s Disease
Authors: Obara Yutaro , Imai Toru , Sato Hidenori , Takeda Yuji , Kato Takeo , Ishii Kuniaki
Published: July 2017

Midnolin (MIDN) was first discovered in embryonic stem cells, but its physiological and pathological roles are, to date, poorly understood. In the present study, we therefore examined the role of MIDN in detail. We found that in PC12 cells, a model of neuronal cells, MIDN localized primarily to the nucleus and intracellular membranes. Nerve growth factor promoted MIDN gene expression, which was attenuated by specific inhibitors of extracellular signal-regulated kinases 1/2 and 5. MIDN-deficient PC12 cells created using CRISPR/Cas9 technology displayed significantly impaired neurite outgrowth. Interestingly, a genetic approach revealed that 10.5% of patients with sporadic Parkinson’s disease (PD) had a lower MIDN gene copy number whereas no copy number variation was observed in healthy people, suggesting that MIDN is involved in PD pathogenesis. Furthermore, the expression of parkin, a major causative gene in PD, was significantly reduced by CRISPR/Cas9 knockout and siRNA knockdown of MIDN. Activating transcription factor 4 (ATF4) was also down-regulated, which binds to the cAMP response element (CRE) in the parkin core promoter region. The activity of CRE was reduced following MIDN loss. Overall, our data suggests that MIDN promotes the expression of parkin E3 ubiquitin ligase, and that MIDN loss can trigger PD-related pathogenic mechanisms.
Human pursuance of equality hinges on mental processes of projecting oneself into the perspectives of others and into future situations
Authors: Takesue Hirofumi , Miyauchi Carlos Makoto , Sakaiya Shiro , Fan Hongwei , Matsuda Tetsuya , Kato Junko
Published: July 2017

In the pursuance of equality, behavioural scientists disagree about distinct motivators, that is, consideration of others and prospective calculation for oneself. However, accumulating data suggest that these motivators may share a common process in the brain whereby perspectives and events that did not arise in the immediate environment are conceived. To examine this, we devised a game imitating a real decision-making situation regarding redistribution among income classes in a welfare state. The neural correlates of redistributive decisions were examined under contrasting conditions, with and without uncertainty, which affects support for equality in society. The dorsal anterior cingulate cortex (dACC) and the caudate nucleus were activated by equality decisions with uncertainty but by selfless decisions without uncertainty. Activation was also correlated with subjective values. Activation in both the dACC and the caudate nucleus was associated with the attitude to prefer accordance with others, whereas activation in the caudate nucleus reflected that the expected reward involved the prospective calculation of relative income. The neural correlates suggest that consideration of others and prospective calculation for oneself may underlie the support for equality. Projecting oneself into the perspective of others and into prospective future situations may underpin the pursuance of equality.
Fatty Acid Uptake in T Cell Subsets Using a Quantum Dot Fatty Acid Conjugate
Authors: Muroski Megan E. , Miska Jason , Chang Alan L. , Zhang Peng , Rashidi Aida , Moore Haley , Lopez-Rosas Aurora , Han Yu , Lesniak Maciej S.
Published: July 2017

Fatty acid (FA) metabolism directly influences the functional capabilities of T cells in tumor microenvironments. Thus, developing tools to interrogate FA-uptake by T cell subsets is important for understanding tumor immunosuppression. Herein, we have generated a novel FA-Qdot 605 dye conjugate with superior sensitivity and flexibility to any of the previously commercially available alternatives. For the first time, we demonstrate that this nanoparticle can be used as a specific measure of fatty acid uptake by T cells both in-vitro and in-vivo. Flow cytometric analysis shows that both the location and activation status of T cells determines their FA uptake. Additionally, CD4+ Foxp3+ regulatory T cells (Tregs) uptake FA at a higher rate than effector T cell subsets, supporting the role of FA metabolism for Treg function. Furthermore, we are able to simultaneously detect glucose and fatty acid uptake directly within the tumor microenvironment. Cumulatively, our results suggest that this novel fluorescent probe is a powerful tool to understand FA utilization within the tumor, thereby providing an unprecedented opportunity to study T cell FA metabolism in-vivo.
Time-averaged disease activity fits better joint destruction in rheumatoid arthritis
Authors: Tsuji Hideaki , Yano Koichiro , Furu Moritoshi , Yamakawa Noriyuki , Ikari Katsunori , Hashimoto Motomu , Ito Hiromu , Fujii Takao , Yamamoto Wataru , Ohmura Koichiro , Taniguchi Atsuo , Momohara Shigeki , Matsuda Fumihiko , Allaart Cornelia F. , Yamanaka Hisashi , Mimori Tsuneyo , Terao Chikashi
Published: July 2017

Disease activity of rheumatoid arthritis (RA), evaluated as Disease Activity Score (DAS), is associated with joint destruction. Since joint destruction reflects the history of disease activities, we hypothesized that time-averaged disease activity would better correlate with joint destruction than one-time disease activity. We recruited RA patients in IORRA (n = 557) and KURAMA (n = 204) cohorts, and calculated time-averaged DAS28 to model a modified Sharp/van der Heijde score (SHS). We evaluated the fitting of the model using time-averaged DAS28 among 1000 models in which we randomly picked up one-time DAS28. We also used clinical disease activity index (CDAI) or data in the BeSt study (European population). After conditioning on autoantibody and disease duration, time-averaged DAS28 showed significant improvement of model fitting compared with one-time DAS28 in both cohorts (p = 0.001 and 0.034, respectively). Time-averaged CDAI also showed a better fit. Integration of multiple DAS fit SHS better in the BeSt study. A good fit of time-averaged DAS could be observed using five to six time points of DAS. In conclusion, time-averaged disease activity fits the joint destruction model better than one-time disease activity. Usage of time-averaged disease activity as a covariate would increase the power of studies to identify novel correlates of joint destruction.
Heterologous prion-forming proteins interact to cross-seed aggregation in Saccharomyces cerevisiae
Authors: Keefer Kathryn M. , Stein Kevin C. , True Heather L.
Published: July 2017

The early stages of protein misfolding remain incompletely understood, as most mammalian proteinopathies are only detected after irreversible protein aggregates have formed. Cross-seeding, where one aggregated protein templates the misfolding of a heterologous protein, is one mechanism proposed to stimulate protein aggregation and facilitate disease pathogenesis. Here, we demonstrate the existence of cross-seeding as a crucial step in the formation of the yeast prion [PSI+], formed by the translation termination factor Sup35. We provide evidence for the genetic and physical interaction of the prion protein Rnq1 with Sup35 as a predominant mechanism leading to self-propagating Sup35 aggregation. We identify interacting sites within Rnq1 and Sup35 and determine the effects of breaking and restoring a crucial interaction. Altogether, our results demonstrate that single-residue disruption can drastically reduce the effects of cross-seeding, a finding that has important implications for human protein misfolding disorders.
The Location of the Deepest Point of the Eyeball Determines the Optic Disc Configuration
Authors: Kim Yong Chan , Jung Younhea , Park Hae-Young Lopilly , Park Chan Kee
Published: July 2017

Tilted and rotated appearances are hallmarks of the myopic optic disc. As the eyeball grows axially, the posterior pole elongates not only globally but in a localized manner as well. In this process, the optic disc is pulled towards the deepest point of the elongated eyeball, which might result in a change in optic disc configuration. Thus, we hypothesized that analyzing the variation of posterior pole contour can play a major role in understanding optic disc configuration in myopic subjects. By analyzing consecutive images of swept source OCT coronal sections at the posterior pole, the deepest interface between Bruch’s membrane and the choroid could be identified as the deepest point of the eyeball (DPE). The location and the properties of the DPE differed significantly between the 125 eyes of non-glaucomatous myopic group and the 40 eyes of non-glaucomatous emmetropic group classified based on 24 mm axial length. The results suggested that the larger disc to DPE angle and the larger disc to DPE depth strongly predicts the optic disc torsion degree and the optic disc tilt. Our findings suggest that identifying the posterior pole profile plays a major role in understanding the optic disc alterations found in myopic subjects.
Quantifying Magnetic Sensitivity of Radical Pair Based Compass by Quantum Fisher Information
Authors: Guo Li-Sha , Xu Bao-Ming , Zou Jian , Shao Bin
Published: July 2017

The radical pair (RP) based compass is considered as one of the principal models of avian magnetoreception. Different from the conventional approach where the sensitivity of RP based compass is described by the singlet yield, we introduce the quantum Fisher information (QFI), which represents the maximum information about the magnetic field’s direction extracted from the RP state, to quantify the sensitivity of RP based compass. The consistency between our results and experimental observations suggests that the QFI may serve as a measure to describe the sensitivity of RP based compass. Besides, within the framework of quantum metrology, we give two specific possible measurement schemes and find that the conventional singlet yield is corresponding to the measurement of total angular momentum. Moreover, we show that the measurement of fluctuation of the total magnetic moment is much more accurate than the singlet yield measurement, and is close to the optimal measurement scheme. Finally, the effects of entanglement and decoherence are also discussed in the spirit of our approach.
Hepatic metabolic effects of Curcuma longa extract supplement in high-fructose and saturated fat fed rats
Authors: Tranchida Fabrice , Rakotoniaina Zo , Shintu Laetitia , Tchiakpe Léopold , Deyris Valérie , Yemloul Mehdi , Stocker Pierre , Vidal Nicolas , Rimet Odile , Hiol Abel , Caldarelli Stefano
Published: July 2017

The metabolic effects of an oral supplementation with a Curcuma longa extract, at a dose nutritionally relevant with common human use, on hepatic metabolism in rats fed a high fructose and saturated fatty acid (HFS) diet was evaluated. High-resolution magic-angle spinning NMR and GC/MS in combination with multivariate analysis have been employed to characterize the NMR metabolite profiles and fatty acid composition of liver tissue respectively. The results showed a clear discrimination between HFS groups and controls involving metabolites such as glucose, glycogen, amino acids, acetate, choline, lysophosphatidylcholine, phosphatidylethanolamine, and β-hydroxybutyrate as well as an increase of MUFAs and a decrease of n-6 and n-3 PUFAs. Although the administration of CL did not counteract deleterious effects of the HFS diet, some metabolites, namely some n-6 PUFA and n-3 PUFA, and betaine were found to increase significantly in liver samples from rats having received extract of curcuma compared to those fed the HFS diet alone. This result suggests that curcuminoids may affect the transmethylation pathway and/or osmotic regulation. CL extract supplementation in rats appears to increase some of the natural defences preventing the development of fatty liver by acting on the choline metabolism to increase fat export from the liver.
Effect of defects controlled by preparation condition and heat treatment on the ferromagnetic properties of few-layer graphene
Authors: Miao Qinghua , Wang Lidong , Liu Zhaoyuan , Wei Bing , Wang Jinhui , Liu Xiangli , Fei Weidong
Published: July 2017

Magnetism in graphene has stimulated extensive studies to search for novel metal-free magnetic device. In this paper, we use a synthesis method far from equilibrium state named self-propagating high temperature synthesis (SHS) to produce few-layer graphene with different defect contents and then use a heat treatment process (vacuum-annealing and air-cooling) to further control the defects in graphene. We find that the type and content of defects in graphene can be controlled by adjusting the mole ratio of reactants (Mg: CaCO3) for SHS reaction and the temperature of the subsequent heat treatment. The deviation of the ratio of reactants from stoichiometric ratio benefits the production of graphene with higher concentration of defects. It is indicated that the temperature of the heat treatment has remarkable influences on the structure of graphene, Raman-sensitive defects can be recovered partly by heat treatment while IR-sensitive defects are closely related with the oxidation and decomposition of the oxygen-containing groups at elevated temperature. This work indicates that SHS is a promising method to produce graphene with special magnetism, and the heat treatment is an effective way to further adjust the magnetism of graphene. This work sheds light on the study to develop carbon materials with controlled ferromagnetism.
A comparative study of five physiological key parameters between four different human trophoblast-derived cell lines
Authors: Rothbauer Mario , Patel Nilaykumar , Gondola Hajnalka , Siwetz Monika , Huppertz Berthold , Ertl Peter
Published: July 2017

The human placenta plays a crucial role as the interface between mother and fetus. It represents a unique tissue that undergoes morphological as well as functional changes on the cellular and tissue level throughout pregnancy. To better understand how the placenta works, a variety of techniques has been developed to re-create this complex physiological barrier in vitro. However, due to the low availability of freshly isolated primary cells, choriocarcinoma cell lines remain the usual suspects as in vitro models for placental research. Here, we present a comparative study on the functional aspects of the choriocarcinoma cell lines BeWo, JAR and Jeg-3, as well as the first trimester trophoblast cell line ACH-3P as placental in vitro barrier models for endocrine and transport studies. Functional assays including tight junction immunostaining, sodium fluorescein retardation, trans epithelial resistance, glucose transport, hormone secretion as well as size-dependent polystyrene nanoparticle transport were performed using the four cell types to evaluate key functional parameters of each cell line to act a relevant in vitro placental barrier model.
Continental shelves as potential resource of rare earth elements
Authors: Pourret Olivier , Tuduri Johann
Published: July 2017

The results of this study allow the reassessment of the rare earth elements (REE) external cycle. Indeed, the river input to the oceans has relatively flat REE patterns without cerium (Ce) anomalies, whereas oceanic REE patterns exhibit strong negative Ce anomalies and heavy REE enrichment. Indeed, the processes at the origin of seawater REE patterns are commonly thought to occur within the ocean masses themselves. However, the results from the present study illustrate that seawater-like REE patterns already occur in the truly dissolved pool of river input. This leads us to favor a partial or complete removal of the colloidal REE pool during estuarine mixing by coagulation, as previously shown for dissolved humic acids and iron. In this latter case, REE fractionation occurs because colloidal and truly dissolved pools have different REE patterns. Thus, the REE patterns of seawater could be the combination of both intra-oceanic and riverine processes. In this study, we show that the Atlantic continental shelves could be considered potential REE traps, suggesting further that shelf sediments could potentially become a resource for REE, similar to metalliferous deep sea sediments.
Physiological oxygen tension reduces hepatocyte dedifferentiation in in vitro culture
Authors: Guo Ren , Xu Xinxiu , Lu Yuting , Xie Xin
Published: July 2017

Primary hepatocytes cultured in vitro are a powerful tool to study the functions of hepatocytes and to evaluate the metabolism and toxicity of new drugs. However, in vitro culture of hepatocytes has proven to be very difficult. Ordinary culture conditions lead to dedifferentiation of hepatocytes, resulting in rapid change in cell morphology and significant reduction in specific cell functions. In the current study, we show that hepatocyte dedifferentiation is a rapid process under 21% O2 conditions. Hepatocytes cultured in 21% O2 undergo epithelial-to-mesenchymal transition (EMT), obtain fibroblast-like morphology, and show decreased hepatic functions. In contrast, 5% O2 is very effective in maintaining the epithelial morphology and many functions of the primary hepatocytes cultured in vitro for up to five days. These functions include albumin production, glycogen storage, LDL-uptake and CYP450-mediated drug metabolism. Furthermore, we find that 5% O2 can relieve the production of reactive oxygen species (ROS) and decrease the level of DNA damage in primary cultured hepatocytes. In addition, we also show that blocking the ERK and GSK-3β pathways can inhibit the dedifferentiation of hepatocytes to a certain extent. Lowering the oxygen tension in cell culture is easily achievable, we believe it could be combined with other methods, such as the use of small molecule cocktails and 3D culture, to maintain proliferation and functions of primary hepatocytes in vitro.
Distribution of salicifoline in freeze-fixed stems of Magnolia kobus as observed by cryo-TOF-SIMS
Authors: Okumura Wakaba , Aoki Dan , Matsushita Yasuyuki , Yoshida Masato , Fukushima Kazuhiko
Published: July 2017

Alkaloids are basic nitrogen-containing chemicals that have important physiological and pharmacological characteristics. Many vascular plant species contain alkaloids, and their rolesin plantaare of interest. However, the detailed distribution of alkaloids remains unclear because of their low water solubility and low concentrations in plants. In this study, we visualized the distribution of salicifoline, a water-soluble quaternary ammonium alkaloid, in the freeze-fixed stems ofMagnolia kobusby cryo time-of-flight secondary ion mass spectrometry. Most of the salicifoline was distributed in living phloem tissues. In the xylem, salicifoline was detected in ray cells, lignifying wood fibres, and in vessels in the latest annual ring. The salicifoline distribution in the xylem varied with the cell wall formation stage. These results provide new insights into the storage, transportation, and role of the alkaloid salicifoline inM. kobus.
Development and application of a comprehensive analytical workflow for the quantification of non-volatile low molecular weight lipids on archaeological stone tools
Authors: Luong Susan , Hayes Elspeth , Flannery Emma , Sutikna Thomas , Tocheri Matthew W. , Saptomo E. Wahyu , Jatmiko Jatmiko , Roberts Richard G.
Published: July 2017

Use-residues are identified on stone tools in the humid tropics, using GC-MS/MS and a sampling strategy that monitors environmental contamination.
Bromide-assisted catalytic oxidation of lead(ii) solids by chlorine in drinking water distribution systems
Authors: Orta John , Patton Samuel , Liu Haizhou
Published: July 2017

This study investigated the effect of bromide on the oxidation of three lead(ii) solids by chlorine – a redox process critical to the control of lead release in drinking water distribution systems.
Heterogeneous enantioselective synthesis of chromans via the oxa-Michael–Michael cascade reaction synergically catalyzed by grafted chiral bases and inherent hydroxyls on mesoporous silica surface
Authors: Wang Shanshan , He Jing , An Zhe
Published: July 2017

A heterogeneous enantioselective oxa-Michael–Michael reaction for the synthesis of chromans has been developed on bifunctional catalysts, resulting in excellent catalytic performance.
Structural-failure resistance of metal–organic frameworks toward multiple-cycle CO2 sorption
Authors: Hu Zhigang , Sun Yao , Zeng Kaiyang , Zhao Dan
Published: July 2017

We present the first study on the structural-failure of MOFs induced by multiple-cycle CO2 adsorption and desorption, wherein UiO-66(Zr) demonstrates a much better resistance than HKUST-1 in 500-cycle CO2 adsorption–desorption tests.
A switchable electrochromism and electrochemiluminescence bifunctional sensor based on the electro-triggered isomerization of spiropyran/layered double hydroxides
Authors: Li Zhixiong , Zhou Yuqiong , Peng Liuqi , Yan Dongpeng , Wei Min
Published: July 2017

A bifunctional ultrathin film electrode was fabricated based on layered double hydroxides and spiropyran, which exhibited electrochromism and electrochemiluminescence sensing behavior toward temperature and Zn2+ ions.
A CuI/CuIII prototypical organometallic mechanism for the deactivation of an active pincer-like CuI catalyst in Ullmann-type couplings
Authors: Rovira Mireia , Jašíková Lucie , Andris Erik , Acuña-Parés Ferran , Soler Marta , Güell Imma , Wang Ming-Zheng , Gómez Laura , Luis Josep M. , Roithová Jana , Ribas Xavi
Published: July 2017

Decomposition pathways in Ullmann C–O couplings have been studied by helium tagging IRPD and DFT studies, supporting aryl–CuIII intermediate species.
Structural complexity induced by topology change in hybrids consisting of hexa-peri-hexabenzocoronene and polyhedral oligomeric silsesquioxane
Authors: Zhang Meng-Yao , Zhou Sheng , Pan Hong-Bing , Ping Jing , Zhang Wei , Fan Xing-He , Shen Zhihao
Published: July 2017

Increasing POSS content (or changing topology) of organic–inorganic hybrids with HBC and POSS results in more complex self-assembled structures. This work provides a new approach for the design and synthesis of materials with sub-10 nm sizes.
Sputtering gold nanoparticles on nanoporous bismuth vanadate for sensitive and selective photoelectrochemical aptasensing of thrombin
Authors: Xin Yanmei , Zhao Yina , Qiu Beilei , Zhang Zhonghai
Published: July 2017

An efficient photoelectrochemical aptasensor based on sputtering Au NP-modified nanoporous BiVO4 was rationally designed and fabricated, and it exhibited excellent sensitivity and selectivity for the detection of thrombin with a low detection limit of 0.5 pM.
Correction: A new AIE multi-block polyurethane copolymer material for subcellular microfilament imaging in living cells
Authors: Niu Yu-qing , He Tao , Song Jun , Chen Si-ping , Liu Xiang-yu , Chen Zhi-gang , Yu Ying-jie , Chen Shi-guo
Published: July 2017

Correction for ‘A new AIE multi-block polyurethane copolymer material for subcellular microfilament imaging in living cells’ by Yu-qing Niu et al., Chem. Commun., 2017, DOI: 10.1039/c7cc02555f.
Controllable synthesis of perovskite-like PbBiO2Cl hollow microspheres with enhanced photocatalytic activity for antibiotic removal
Authors: Yin Sheng , Wu Ting , Li Ming , Di Jun , Ji Mengxia , Wang Bin , Chen Yong , Xia Jiexiang , Li Huaming
Published: July 2017

Novel perovskite-like PbBiO2Cl materials with hollow and porous sphere-like structures were successfully synthesized using a polyvinyl pyrrolidone (PVP) and 1-hexadecyl-3-methylimidazolium chlorine ([C16mim]Cl) complex system.