bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal relationships between glycemic status and body mass index in a multiethnic study: evidence from observational and genetic epidemiology
Authors: Ishola Adeola F. , Gerstein Hertzel C. , Engert James C. , Mohan Viswanathan , Diaz Rafael , Anand Sonia S. , Meyre David 
Published: August 2016

AbstractWe investigated the relationship between glycemic status and BMI and its interaction with obesity single-nucleotide polymorphisms (SNPs) in a multi-ethnic longitudinal cohort at high-risk for dysglycemia. We studied 17 394 participants from six ethnicities followed-up for 3.3 years. Twenty-three obesity SNPs were genotyped and an unweighted genotype risk score (GRS) was calculated. Glycemic status was defined using an oral glucose tolerance test. Linear regression models were adjusted for age, sex and population stratification. Normal glucose tolerance (NGT) to dysglycemia transition was associated with baseline BMI and BMI change. Impaired fasting glucose/impaired glucose tolerance to type 2 diabetes transition was associated with baseline BMI but not BMI change. No simultaneous significant main genetic effects and interactions between SNPs/GRS and glycemic status or transition on BMI level and BMI change were observed. Our data suggests that the interplay between glycemic status and BMI trajectory may be independent of the effects of obesity genes. This implies that individuals with different glycemic statuses may be combined together in genetic association studies on obesity traits, if appropriate adjustments for glycemic status are performed. Implementation of population-wide weight management programs may be more beneficial towards individuals with NGT than those at a later disease stage.
Protein Inhibitor of NOS1 Plays a Central Role in the Regulation of NOS1 Activity in Human Dilated Hearts
Authors: Roselló-Lletí Esther , Tarazón Estefanía , Ortega Ana , Gil-Cayuela Carolina , Carnicer Ricardo , Lago Francisca , González-Juanatey Jose Ramón , Portolés Manuel , Rivera Miguel 
Published: August 2016

AbstractAn essential factor for the production of nitric oxide by nitric oxide synthase 1 (NOS1), major modulator of cardiac function, is the cofactor tetrahydrobiopterin (BH4). BH4 is regulated by GTP cyclohydrolase 1, the rate-limiting enzyme in BH4 biosynthesis which catalyses the formation of dihydroneopterin 3′triphosfate from GTP, producing BH4 after two further steps catalyzed by 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase. However, there are other essential factors involved in the regulation of NOS1 activity, such as protein inhibitor of NOS1 (PIN), calmodulin, heat shock protein 90 and NOS interacting protein. All these molecules have never been analysed in human non-ischemic dilated hearts (DCM). In this study we demonstrated that the upregulation of cardiac NOS1 is not accompanied by increased NOS1 activity in DCM, partly due to the elevated PIN levels and not because of alterations in biopterin biosynthesis. Notably, the PIN concentration was significantly associated with impaired ventricular function, highlighting the importance of this NOS1 activity inhibitor in Ca2+ homeostasis. These results take a central role in the current list of targets for future studies focused on the complex cardiac dysfunction processes through more efficient harnessing of NOS1 signalling.
Autapse-induced multiple coherence resonance in single neurons and neuronal networks
Authors: Yilmaz Ergin , Ozer Mahmut , Baysal Veli , Perc Matjaž 
Published: August 2016

AbstractWe study the effects of electrical and chemical autapse on the temporal coherence or firing regularity of single stochastic Hodgkin-Huxley neurons and scale-free neuronal networks. Also, we study the effects of chemical autapse on the occurrence of spatial synchronization in scale-free neuronal networks. Irrespective of the type of autapse, we observe autaptic time delay induced multiple coherence resonance for appropriately tuned autaptic conductance levels in single neurons. More precisely, we show that in the presence of an electrical autapse, there is an optimal intensity of channel noise inducing the multiple coherence resonance, whereas in the presence of chemical autapse the occurrence of multiple coherence resonance is less sensitive to the channel noise intensity. At the network level, we find autaptic time delay induced multiple coherence resonance and synchronization transitions, occurring at approximately the same delay lengths. We show that these two phenomena can arise only at a specific range of the coupling strength and that they can be observed independently of the average degree of the network.
Erythropoietin treatment in murine multiple myeloma: immune gain and bone loss
Authors: Deshet-Unger Naamit , Hiram-Bab Sahar , Haim-Ohana Yasmin , Mittelman Moshe , Gabet Yankel , Neumann Drorit 
Published: August 2016

AbstractMultiple myeloma (MM) is a plasma cell malignancy, characterized by osteolytic lesions and monoclonal immunoglobulins. The anemia, accompanying the disease is often treated with recombinant human EPO. Diverse non-erythropoietic effects of EPO have led us to question its combined action on the immune system and bone in the 5T33MM mouse model. EPO administration to MM mice attenuated disease progression as demonstrated by a decrease in serum MM IgG2b, splenic CD138 expressing cells, IL-6 and RORγτ transcripts in bone marrow (BM). IFN-γ transcript levels and macrophages (F4/80+CD11b+) in the BM both increased ~1.5 fold in the EPO-treated MM mice. In-vitro, EPO stimulated phagocytosis of 5T33MM cells (+30%) by BM-derived macrophages. In contrast, high-resolution microCT analysis of distal femurs revealed EPO-associated bone loss in both healthy and 5T33MM mice. EPO significantly increased expression of the osteoclastogenic nuclear factor-kappa B ligand (RANKL) in healthy mice, but not in MM mice, likely due to antagonizing effects on MM progression. Thus, in MM, EPO may act as a double-edged-sword stimulating immune response, while accelerating bone resorption, possibly via direct action on BM macrophages. This study supports a prudent approach of treating anemia in MM patients, aiming to maintain EPO-associated anti-MM effects, while considering bone damage.
Distinct oxytocin effects on belief updating in response to desirable and undesirable feedback
Authors: Ma Yina , Li Shiyi , Wang Chenbo , Liu Yi , Li Wenxin , Yan Xinyuan , Chen Qiang , Han Shihui 
Published: August 2016

Significance
People tend to incorporate desirable feedback into their beliefs but discount undesirable ones. Such optimistic updating has evolved as an advantageous mechanism for social adaptation and physical/mental health. Here, in three independent studies, we show that intranasally administered oxytocin (OT), an evolutionary ancient neuropeptide pivotal to social adaptation, augments optimistic belief updating by increasing updates and learning of desirable feedback but impairing updates of undesirable feedback. Moreover, the OT-impaired updating of undesirable feedback is more salient in individuals with high, rather than with low, depression or anxiety traits. OT also increases second-order confidence judgment after desirable feedback. These findings reveal a molecular substrate underlying the formation of optimistic beliefs about the future.
Axitinib blocks Wnt/β-catenin signaling and directs asymmetric cell division in cancer
Authors: Qu Yi , Gharbi Naouel , Yuan Xing , Olsen Jan Roger , Blicher Pernille , Dalhus Bjørn , Brokstad Karl A. , Lin Biaoyang , Øyan Anne Margrete , Zhang Weidong , Kalland Karl-Henning , Ke Xisong 
Published: August 2016

Significance
The Wnt (wingless)/β-catenin signaling pathway is an attractive target for cancer therapy. However, known Wnt inhibitors are still far from clinical use. Here we report that the clinically approved drug axitinib strongly inhibits Wnt/β-catenin signaling in vitro and in vivo. In particular, a phenotype of Wnt inhibition called “Wnt asymmetry” was revealed in axitinib-treated cancer cells. The identification of E3 ubiquitin ligase SHPRH (SNF2, histone-linker, PHD and RING finger domain-containing helicase) as the functional target implies that axitinib blocking of Wnt signaling is independent of genetic mutations that are frequently observed in cancer patients. Collectively, our results suggest a mechanism of nuclear β-catenin regulation and highlight axitinib as a promising therapeutic agent for cancer patients with aberrant Wnt/β-catenin signaling.
Timing and causes of mid-Holocene mammoth extinction on St. Paul Island, Alaska
Authors: Graham Russell W. , Belmecheri Soumaya , Choy Kyungcheol , Culleton Brendan J. , Davies Lauren J. , Froese Duane , Heintzman Peter D. , Hritz Carrie , Kapp Joshua D. , Newsom Lee A. , Rawcliffe Ruth , Saulnier-Talbot Émilie , Shapiro Beth , Wang Yue , Williams John W. , Wooller Matthew J. 
Published: August 2016

Significance
St. Paul Island, Alaska, is famous for its late-surviving population of woolly mammoth. The puzzle of mid-Holocene extinction is solved via multiple independent paleoenvironmental proxies that tightly constrain the timing of extinction to 5,600 ± 100 y ago and strongly point to the effects of sea-level rise and drier climates on freshwater scarcity as the primary extinction driver. Likely ecosystem effects of the mega-herbivore extinction include reduced rates of watershed erosion by elimination of crowding around water holes and a vegetation shift toward increased abundances of herbaceous taxa. Freshwater availability may be an underappreciated driver of island extinction. This study reinforces 21st-century concerns about the vulnerability of island populations, including humans, to future warming, freshwater availability, and sea level rise.
Extensive phosphorylation of AMPA receptors in neurons
Authors: Diering Graham H. , Heo Seok , Hussain Natasha K. , Liu Bian , Huganir Richard L. 
Published: August 2016

Significance
Decades of research from many laboratories has established a model in which phosphorylation of the GluA1 AMPA-type glutamate receptor subunit plays a significant role modulating long-term potentiation and depression, homeostatic and neuromodulator-regulated plasticity, spatial memory, fear/extinction, and appetitive incentive learning. However, a recent study suggests that GluA1 phosphorylation is exceedingly low, even in synaptic fractions. Here, we address this controversy using in vitro and in vivo techniques. We find a large fraction of excitatory synapses are positive for phosphorylated GluA1. Moreover, phosphorylated species make up a significant fraction of the population and are highly responsive to numerous physiologically relevant stimuli. This characterization reaffirms a large body of work defining a prominent role of AMPA receptor phosphorylation in synapse biology and synaptic plasticity.
Biodiversity analysis in the digital era
Authors: La Salle John , Williams Kristen J. , Moritz Craig 
Published: August 2016

This paper explores what the virtual biodiversity e-infrastructure will look like as it takes advantage of advances in ‘Big Data’ biodiversity informatics and e-research infrastructure, which allow integration of various taxon-level data types (genome, morphology, distribution and species interactions) within a phylogenetic and environmental framework. By overcoming the data scaling problem in ecology, this integrative framework will provide richer information and fast learning to enable a deeper understanding of biodiversity evolution and dynamics in a rapidly changing world. The Atlas of Living Australia is used as one example of the advantages of progressing towards this future. Living in this future will require the adoption of new ways of integrating scientific knowledge into societal decision making.
This article is part of the themed issue ‘From DNA barcodes to biomes’.
Bayesian Inference of Two-Dimensional Contrast Sensitivity Functions
Authors: Wang Xiaoxiao , Wang Huan , Huang Jinfeng , Tzvetanov Tzvetomir , Zhou Yifeng 
Published: August 2016

AbstractThe contrast sensitivity function (CSF) is crucial in predicting functional vision both in research and clinical areas. Recently, a group of novel strategies, multi-dimensional adaptive methods, were proposed and allowed more rapid measurements when compared to usual methods such as Ψ or staircase. Our study further presents a multi-dimensional Bayesian framework to estimate parameters of the CSF from experimental data obtained by classical sampling. We extensively simulated the framework’s performance as well as validated the results in a psychophysical experiment. The results showed that the Bayesian framework significantly improves the accuracy and precision of parameter estimates from usual strategies, and requires about the same number of observations as the novel methods to obtain reliable inferences. Additionally, the improvement with the Bayesian framework was maintained when the prior poorly matched the observer’s CSFs. The results indicated that the Bayesian framework is flexible and sufficiently precise for estimating CSFs.
Different combinations of ErbB receptor dimers generate opposing signals that regulate cell proliferation in cardiac valve development
Authors: Iwamoto Ryo , Mine Naoki , Mizushima Hiroto , Mekada Eisuke 
Published: August 2016

AbstractHB-EGF plays an indispensable role in suppression of cell proliferation in mouse valvulogenesis. However, ligands of the EGF receptor (EGFR/ErbB1), including HB-EGF, are generally considered as growth-promoting factors, as shown in cancers. HB-EGF binds to and activates ErbB1 and ErbB4. We investigated the role of ErbB receptors in valvulogenesis in vivo using ErbB1- and ErbB4-deficient mice, and an ex vivo model of endocardial cushion explants. We show that HB-EGF suppresses valve mesenchymal cell proliferation through a heterodimer of ErbB1 and ErbB4, and an ErbB1 ligand(s) promotes cell proliferation through a homodimer of ErbB1. Moreover, a rescue experiment with cleavable or uncleavable isoforms of ErbB4 inERBB4null cells suggests that the cytoplasmic intracellular domain of ErbB4, rather than the membrane-anchored tyrosine kinase, achieves this suppression. Our study demonstrates that opposing signals generated by different ErbB dimer combinations function in the same cardiac cushion mesenchymal cells for proper cardiac valve formation.Summary statementIn valvulogenesis, opposing signals generated by different combinations of ErbB-dimers elaborately regulate cell proliferation, in which proteolytically released intracellular domain of ErbB4 activated by HB-EGF is required to suppress proliferation.
Changes in Stomatal Behavior and Guard Cell Cytosolic Free Calcium in Response to Oxidative Stress
Authors: McAinsh M. R. , Clayton H. , Mansfield T. A. , Hetherington A. M. 
Published: August 2016

Abstract
We have investigated the cellular basis for the effects of oxidative stress on stomatal behavior using stomatal bioassay and ratio photometric techniques. Two oxidative treatments were employed in this study: (a) methyl viologen, which generates superoxide radicals, and (b) H2O2. Both methyl viologen and H2O2 inhibited stomatal opening and promoted stomatal closure. At concentrations [less than or equal to]10–5 M, the effects of methyl viologen and H2O2 on stomatal behavior were reversible and were abolished by 2 mM EGTA or 10 [mu]M verapamil. In addition, at 10–5 M, i.e. the maximum concentration at which the effects of the treatments were prevented by EGTA or verapamil, methyl viologen and H2O2 caused an increase in guard cell cytosolic free Ca2+ ([Ca2+]i), which was abolished in the presence of EGTA. Therefore, at low concentrations of methyl viologen and H2O2, removal of extracellular Ca2+ prevented both the oxidative stress-induced changes in stomatal aperture and the associated increases in [Ca2+]i. This suggests that in this concentration range the effects of the treatments are Ca2+-dependent and are mediated by changes in [Ca2+]i. In contrast, at concentrations of methyl viologan and H2O2 &gt; 10–5 M, EGTA and verapamil had no effect. However, in this concentration range the effects of the treatments were irreversible and correlated with a marked reduction in membrane integrity and guard cell viability. This suggests that at high concentrations the effects of methyl viologen and H2O2 may be due to changes in membrane integrity. The implications of oxidative stress-induced increases in [Ca2+]i and the possible disruption of guard-cell Ca2+ homeostasis are discussed in relation to the processes of Ca2+-based signal transduction in stomatal guard cells and the control of stomatal aperture.
Characterization of Glutathione Uptake in Broad Bean Leaf Protoplasts
Authors: Jamai A. , Tommasini R. , Martinoia E. , Delrot S. 
Published: August 2016

Abstract
Transport of reduced glutathione (GSH) and oxidized glutathione (GSSG) was studied with broad bean (Vicia faba L.) leaf tissues and protoplasts. Protoplasts and leaf discs took up GSSG at a rate about twice the uptake rate of GSH. Detailed studies with protoplasts indicated that GSH and GSSG uptake exhibited the same sensitivity to the external pH and to various chemical reagents. GSH uptake was inhibited by GSSG and glutathione conjugates. GSSG uptake was inhibited by GSH and GS conjugates, and the uptake of metolachlor-GS was inhibited by GSSG. Various amino acids (L-glutamic acid, L-glutamine, L-cysteine, L-glycine, L-methionine) and peptides (glycine-glycine, glycine-glycine-glycine) affected neither the transport of GSH nor GSSG. Uptake kinetics indicate that GSH is taken up by a single saturable transporter, with an apparent Km of 0.4 mM, whereas GSSG uptake exhibits two saturable phases, with an apparent Km of 7 [mu]M and 3.7 mM. It is concluded that the plasma membrane of leaf cells contains a specific transport system for glutathione, which takes up GSSG and GS conjugates preferentially over GSH. Proton flux measurements and electrophysiological measurements indicate that GSH and GSSG are taken up with proton symport. However, a detailed analysis of these measurements suggests that the ion movements induced by GSSG differ from those induced by GSH.
Evidence That the Pathway of Dimethylsulfoniopropionate Biosynthesis Begins in the Cytosol and Ends in the Chloroplast
Authors: Trossat C. , Nolte K. D. , Hanson A. D. 
Published: August 2016

Abstract
In the flowering plant Wollastonia biflora (L.) DC. the first step in 3-dimethylsulfoniopropionate (DMSP) synthesis is conversion of methionine to S-methylmethionine (SMM) and the last is oxidation of 3-dimethylsulfoniopropionaldehyde (DMSP-ald) (F. James, L. Paquet, S.A. Sparace, D.A. Gage, A.D. Hanson [1995] Plant Physiol 108: 1439–1448). DMSP-ald was shown to undergo rapid, spontaneous decomposition to dimethylsulfide and acrolein. However, it was stable enough (half-life [greater than or equal to] 1 h) in tertiary amine buffers to use as a substrate for enzyme assays. A dehydrogenase catalyzing DMSP-ald oxidation was detected in extracts of W. biflora mesophyll protoplasts. This enzyme had a high affinity for DMSP-ald (Km = 1.5 [mu]M), was subject to substrate inhibition, preferred NAD to NADP, and was immunologically related to plant betaine aldehyde dehydrogenases. After fractionation of protoplast lysates, [greater than or equal to]90% of DMSP-ald dehydrogenase activity was recovered from the chloroplast stromal fraction, whereas the enzyme that mediates SMM synthesis, S-adenosylmethionine:methionine S-methyltransferase, was found exclusively in the cytosolic fraction. Immunohistochemical analysis confirmed that the S-methyltransferase was cytosolic. Intact W. biflora chloroplasts were able to metabolize supplied [35S]SMM to [35S]DMSP. These findings indicate that SMM is made in the cytosol, imported into the chloroplast, and there converted successively to DMSP-ald and DMSP.
Photosynthetic Gene Expression in Meristems and during Initial Leaf Development in a C4 Dicotyledonous Plant
Authors: Ramsperger V. C. , Summers R. G. , Berry J. O. 
Published: August 2016

Abstract
Immunolocalization and fluorescent in situ hybridization were used with confocal microscopy to examine patterns of photosynthetic gene expression during initial stages of leaf development in the C4 dicot Amaranthus hypochondriacus. mRNAs encoding the large and small subunit of ribulose-1,5-bisphosphate carboxylase were present in the apical dome and in all cells of the leaf primordia. In contrast, these polypeptides were detected only in cells of the ground meristem, with no accumulation detected in the apical dome or in other leaf primordia cells. The ribulose-1,5-bisphosphate carboxylase transcripts showed very little cell-type specificity as leaf structures began to differentiate, whereas their polypeptides accumulated primarily in bundle-sheath precursor cells. Phosphoenolpyruvate carboxylase and pyruvate orthophosphate dikinase mRNAs were abundant in meristems and leaf primordia, although their corresponding polypeptides did not accumulate in leaves until the leaf vascular system began to differentiate. These polypeptides were mostly restricted to premesophyll cells from their earliest detection, whereas their transcripts remained present in nearly all leaf cells. These findings indicate that individual C4 genes are independently regulated as they become initially localized to their appropriate cell types. Furthermore, posttranscriptional regulation plays a major role in determining early patterns of C4 gene expression.
Comparative analysis of book tags: a cross-lingual perspective
Authors: Lu Chao , Zhang Chengzhi , He Daqing 
Published: August 2016

Purpose
In the era of social media, users all over the world annotate books with social tags to express their preferences and interests. The purpose of this paper is to explore different tagging behaviours by analysing the book tags in different languages.

Design/methodology/approach
This investigation collected nearly 56,000 tags of 1,200 books from one Chinese and two English online bookmarking systems; it combined content analysis and machine-processing methods to evaluate the similarities and differences between different tagging systems from a cross-lingual perspective. Jaccard’s coefficient was adopted to evaluate the similarity level.

Findings
The results show that the similarity between mono-lingual tags of the same books is higher than that of cross-lingual tags in different systems and the similarity between tags of books written for specialties is higher than that of books written for the general public.

Research limitations/implications
Those who have more in common annotate books with more similar tags. The similarity between users in tagging systems determines the similarity of the tag sets.

Practical implications
The results and conclusion of this study will benefit users’ cross-lingual information retrieval and cross-lingual book recommendation for online bookmarking systems.

Originality/value
This study may be one of the first to compare cross-lingual tags. Its methodology can be applied to tag comparison between any two languages. The insights of this study will help develop cross-lingual tagging systems and improve information retrieval.