bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic sharing and heritability of paediatric age of onset autoimmune diseases
Authors: Li Yun R. , Zhao Sihai D. , Li Jin , Bradfield Jonathan P. , Mohebnasab Maede , Steel Laura , Kobie Julie , Abrams Debra J. , Mentch Frank D. , Glessner Joseph T. , Guo Yiran , Wei Zhi , Connolly John J. , Cardinale Christopher J. , Bakay Marina , Li Dong , Maggadottir S. Melkorka , Thomas Kelly A. , Qui Haijun , Chiavacci Rosetta M. , Kim Cecilia E. , Wang Fengxiang , Snyder James , Flatø Berit , Førre Øystein , Denson Lee A. , Thompson Susan D. , Becker Mara L. , Guthery Stephen L. , Latiano Anna , Perez Elena , Resnick Elena , Strisciuglio Caterina , Staiano Annamaria , Miele Erasmo , Silverberg Mark S. , Lie Benedicte A. , Punaro Marilynn , Russell Richard K. , Wilson David C. , Dubinsky Marla C. , Monos Dimitri S. , Annese Vito , Munro Jane E. , Wise Carol , Chapel Helen , Cunningham-Rundles Charlotte , Orange Jordan S. , Behrens Edward M. , Sullivan Kathleen E. , Kugathasan Subra , Griffiths Anne M. , Satsangi Jack , Grant Struan F. A. , Sleiman Patrick M. A. , Finkel Terri H. , Polychronakos Constantin , Baldassano Robert N. , Luning Prak Eline T. , Ellis Justine A. , Li Hongzhe , Keating Brendan J. , Hakonarson Hakon 
Published: October 2015

AbstractAutoimmune diseases (AIDs) are polygenic diseases affecting 7–10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h2). SNP-h2 estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP-h2 in T1D and JIA, but does not significantly contribute to the pairwise rG. Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts.
Hyperpolarized nanodiamond with long spin-relaxation times
Authors: Rej Ewa , Gaebel Torsten , Boele Thomas , Waddington David E.J. , Reilly David J. 
Published: October 2015

AbstractThe use of hyperpolarized agents in magnetic resonance, such as 13C-labelled compounds, enables powerful new imaging and detection modalities that stem from a 10,000-fold boost in signal. A major challenge for the future of the hyperpolarization technique is the inherently short spin-relaxation times, typically <60 s for 13C liquid-state compounds, which limit the time that the signal remains boosted. Here we demonstrate that 1.1% natural abundance 13C spins in synthetic nanodiamond can be hyperpolarized at cryogenic and room temperature without the use of free radicals, and, owing to their solid-state environment, exhibit relaxation times exceeding 1 h. Combined with the already established applications of nanodiamonds in the life sciences as inexpensive fluorescent markers and non-cytotoxic substrates for gene and drug delivery, these results extend the theranostic capabilities of nanoscale diamonds into the domain of hyperpolarized magnetic resonance.
Immunological biomarkers predict HIV-1 viral rebound after treatment interruption
Authors: Hurst Jacob , Hoffmann Matthias , Pace Matthew , Williams James P. , Thornhill John , Hamlyn Elizabeth , Meyerowitz Jodi , Willberg Chris , Koelsch Kersten K. , Robinson Nicola , Brown Helen , Fisher Martin , Kinloch Sabine , Cooper David A. , Schechter Mauro , Tambussi Giuseppe , Fidler Sarah , Babiker Abdel , Weber Jonathan , Kelleher Anthony D. , Phillips Rodney E. , Frater John 
Published: October 2015

AbstractTreatment of HIV-1 infection with antiretroviral therapy (ART) in the weeks following transmission may induce a state of ‘post-treatment control’ (PTC) in some patients, in whom viraemia remains undetectable when ART is stopped. Explaining PTC could help our understanding of the processes that maintain viral persistence. Here we show that immunological biomarkers can predict time to viral rebound after stopping ART by analysing data from a randomized study of primary HIV-1 infection incorporating a treatment interruption (TI) after 48 weeks of ART (the SPARTAC trial). T-cell exhaustion markers PD-1, Tim-3 and Lag-3 measured prior to ART strongly predict time to the return of viraemia. These data indicate that T-cell exhaustion markers may identify those latently infected cells with a higher proclivity to viral transcription. Our results may open new avenues for understanding the mechanisms underlying PTC, and eventually HIV-1 eradication.
Substrate specificity and transport mechanism of amino-acid transceptor Slimfast from Aedes aegypti
Authors: Boudko Dmitri Y. , Tsujimoto Hitoshi , Rodriguez Stacy D. , Meleshkevitch Ella A. , Price David P. , Drake Lisa L. , Hansen Immo A. 
Published: October 2015

AbstractAnautogenous mosquitoes depend on vertebrate blood as nutrient source for their eggs. A highly efficient set of membrane transporters mediates the massive movement of nutrient amino acids between mosquito tissues after a blood meal. Here we report the characterization of the amino-acid transporter Slimfast (Slif) from the yellow-fever mosquito Aedes aegypti using codon-optimized heterologous expression. Slif is a well-known component of the target-of-rapamycin signalling pathway and fat body nutrient sensor, but its substrate specificity and transport mechanism were unknown. We found that Slif transports essential cationic and neutral amino acids with preference for arginine. It has an unusual dual-affinity mechanism with only the high affinity being Na+ dependent. Tissue-specific expression and blood meal-dependent regulation of Slif are consistent with conveyance of essential amino acids from gut to fat body. Slif represents a novel transport system and type of transceptor for sensing and transporting essential amino acids during mosquito reproduction.
Selective hydrogenation of 1,3-butadiene on platinum–copper alloys at the single-atom limit
Authors: Lucci Felicia R. , Liu Jilei , Marcinkowski Matthew D. , Yang Ming , Allard Lawrence F. , Flytzani-Stephanopoulos Maria , Sykes E. Charles H. 
Published: October 2015

AbstractPlatinum is ubiquitous in the production sectors of chemicals and fuels; however, its scarcity in nature and high price will limit future proliferation of platinum-catalysed reactions. One promising approach to conserve platinum involves understanding the smallest number of platinum atoms needed to catalyse a reaction, then designing catalysts with the minimal platinum ensembles. Here we design and test a new generation of platinum–copper nanoparticle catalysts for the selective hydrogenation of 1,3-butadiene,, an industrially important reaction. Isolated platinum atom geometries enable hydrogen activation and spillover but are incapable of C–C bond scission that leads to loss of selectivity and catalyst deactivation. γ-Alumina-supported single-atom alloy nanoparticle catalysts with <1 platinum atom per 100 copper atoms are found to exhibit high activity and selectivity for butadiene hydrogenation to butenes under mild conditions, demonstrating transferability from the model study to the catalytic reaction under practical conditions.
Learning of anticipatory responses in single neurons of the human medial temporal lobe
Authors: Reddy Leila , Poncet Marlene , Self Matthew W. , Peters Judith C. , Douw Linda , van Dellen Edwin , Claus Steven , Reijneveld Jaap C. , Baayen Johannes C. , Roelfsema Pieter R. 
Published: October 2015

AbstractNeuronal processes underlying the formation of new associations in the human brain are not yet well understood. Here human participants, implanted with depth electrodes in the brain, learned arbitrary associations between images presented in an ordered, predictable sequence. During learning we recorded from medial temporal lobe (MTL) neurons that responded to at least one of the pictures in the sequence (the preferred stimulus). We report that as a result of learning, single MTL neurons show asymmetric shifts in activity and start firing earlier in the sequence in anticipation of their preferred stimulus. These effects appear relatively early in learning, after only 11 exposures to the stimulus sequence. The anticipatory neuronal responses emerge while the subjects became faster in reporting the next item in the sequence. These results demonstrate flexible representations that could support learning of new associations between stimuli in a sequence, in single neurons in the human MTL.
The external domains of the HIV-1 envelope are a mutational cold spot
Authors: Geller Ron , Domingo-Calap Pilar , Cuevas José M. , Rossolillo Paola , Negroni Matteo , Sanjuán Rafael 
Published: October 2015

AbstractIn RNA viruses, mutations occur fast and have large fitness effects. While this affords remarkable adaptability, it can also endanger viral survival due to the accumulation of deleterious mutations. How RNA viruses reconcile these two opposed facets of mutation is still unknown. Here we show that, in human immunodeficiency virus (HIV-1), spontaneous mutations are not randomly located along the viral genome. We find that the viral mutation rate experiences a threefold reduction in the region encoding the most external domains of the viral envelope, which are strongly targeted by neutralizing antibodies. This contrasts with the hypermutation mechanisms deployed by other, more slowly mutating pathogens such as DNA viruses and bacteria, in response to immune pressure. We show that downregulation of the mutation rate in HIV-1 is exerted by the template RNA through changes in sequence context and secondary structure, which control the activity of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (A3)-mediated cytidine deamination and the fidelity of the viral reverse transcriptase.
Structure of the DBL3X-DBL4ε region of the VAR2CSA placental malaria vaccine candidate: insight into DBL domain interactions
Authors: Gangnard Stéphane , Lewit-Bentley Anita , Dechavanne Sébastien , Srivastava Anand , Amirat Faroudja , Bentley Graham A. , Gamain Benoît 
Published: October 2015

AbstractThe human malaria parasite, Plasmodium falciparum, is able to evade spleen-mediated clearing from blood stream by sequestering in peripheral organs. This is due to the adhesive properties conferred by the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family exported by the parasite to the surface of infected erythrocytes. Expression of the VAR2CSA variant of PfEMP1 leads to pregnancy-associated malaria, which occurs when infected erythrocytes massively sequester in the placenta by binding to low-sulfated Chondroitin Sulfate A (CSA) present in the intervillous spaces. VAR2CSA is a 350 kDa protein that carries six Duffy-Binding Like (DBL) domains, one Cysteine-rich Inter-Domain Regions (CIDR) and several inter-domain regions. In the present paper, we report for the first time the crystal structure at 2.9 Å of a VAR2CSA double domain, DBL3X-DBL4ε, from the FCR3 strain. DBL3X and DBL4ε share a large contact interface formed by residues that are invariant or highly conserved in VAR2CSA variants, which suggests that these two central DBL domains (DBL3X-DBL4ε) contribute significantly to the structuring of the functional VAR2CSA extracellular region. We have also examined the antigenicity of peptides corresponding to exposed loop regions of the DBL4ε structure.
High-Efficiency Cooper-Pair Splitter in Quantum Anomalous Hall Insulator Proximity-Coupled with Superconductor
Authors: Zhang Ying-Tao , Deng Xinzhou , Sun Qing-Feng , Qiao Zhenhua 
Published: October 2015

AbstractThe quantum entanglement between two qubits is crucial for applications in the quantum communication. After the entanglement of photons was experimentally realized, much effort has been taken to exploit the entangled electrons in solid-state systems. Here, we propose a Cooper-pair splitter, which can generate spatially-separated but entangled electrons, in a quantum anomalous Hall insulator proximity-coupled with a superconductor. After coupling with a superconductor, the chiral edge states of the quantum anomalous Hall insulator can still survive, making the backscattering impossible. Thus, the local Andreev reflection becomes vanishing, while the crossed Andreev reflection becomes dominant in the scattering process. This indicates that our device can serve as an extremely high-efficiency Cooper-pair splitter. Furthermore, because of the chiral characteristic, our Cooper-pair splitter is robust against disorders and can work in a wide range of system parameters. Particularly, it can still function even if the system length exceeds the superconducting coherence length.
Absorption of PCB126 by upper airways impairs G protein-coupled receptor-mediated immune response
Authors: Shimada Ana Lúcia B. , Cruz Wesley S. , Loiola Rodrigo A. , Drewes Carine C. , Dörr Fabiane , Figueiredo Natália G. , Pinto Ernani , Farsky Sandra H. P. 
Published: October 2015

AbstractPCB126 is a dioxin-like polychlorinated biphenyl (PCB) environmental pollutant with a significant impact on human health, as it bioaccumulates and causes severe toxicity. PCB126-induced immune toxicity has been described, although the mechanisms have not been fully elucidated. In this study, an in vivo protocol of PCB126 intoxication into male Wistar rats by intranasal route was used, which has not yet been described. The intoxication was characterised by PCB126 accumulation in the lungs and liver and enhanced aryl hydrocarbon receptor expression in the liver, lungs, kidneys and adipose tissues. Moreover, an innate immune deficiency was characterised by impairment of adhesion receptors on blood leukocytes and by reduced blood neutrophil locomotion and oxidative burst activation elicited by ex vivo G protein-coupled receptor (GPCR) activation. Specificity of PCB126 actions on the GPCR pathway was shown by normal burst oxidative activation evoked by Toll-like receptor 4 and protein kinase C direct activation. Moreover, in vivo PCB180 intoxication did not alter adhesion receptors on blood leukocytes either blood neutrophil locomotion and only partially reduced the GPCR-induced burst oxidative activation on neutrophils. Therefore, a novel mechanism of in vivo PCB126 toxicity is described which impairs a pivotal inflammatory pathway to the host defence against infections.
Discovery of Novel Anti-prion Compounds Using In Silico and In Vitro Approaches
Authors: Hyeon Jae Wook , Choi Jiwon , Kim Su Yeon , Govindaraj Rajiv Gandhi , Jam Hwang Kyu , Lee Yeong Seon , An Seong Soo A. , Lee Myung Koo , Joung Jong Young , No Kyoung Tai , Lee Jeongmin 
Published: October 2015

AbstractPrion diseases are associated with the conformational conversion of the physiological form of cellular prion protein (PrPC) to the pathogenic form, PrPSc. Compounds that inhibit this process by blocking conversion to the PrPSc could provide useful anti-prion therapies. However, no suitable drugs have been identified to date. To identify novel anti-prion compounds, we developed a combined structure- and ligand-based virtual screening system in silico. Virtual screening of a 700,000-compound database, followed by cluster analysis, identified 37 compounds with strong interactions with essential hotspot PrP residues identified in a previous study of PrPC interaction with a known anti-prion compound (GN8). These compounds were tested in vitro using a multimer detection system, cell-based assays and surface plasmon resonance. Some compounds effectively reduced PrPSc levels and one of these compounds also showed a high binding affinity for PrPC. These results provide a promising starting point for the development of anti-prion compounds.
Zoophycos macroevolution since 541 Ma
Authors: Zhang Li-Jun , Fan Ruo-Ying , Gong Yi-Ming 
Published: October 2015

AbstractZoophycosis one of the most complex and enigmatic trace fossils recorded in marine strata from Cambrian to Quaternary worldwide, which is invaluable for the study of Phanerozoic development of organism–environment interactions. Here we address and demonstrate the macroevolution of PhanerozoicZoophycosby assembling 448 points in constructing the PhanerozoicZoophycosdatabase based on 291 papers from 1821 to 2015 and 180 specimens from Cambrian to Palaeogene. The comprehensive dataset reveals, for the first time, five peaks and six depressions in PhanerozoicZoophycosoccurrence frequency. Secondly, the palaeogeographical distribution ofZoophycosis closely associated with the supercontinent Pangaea shifting, independent of the latitude. Our data also attest that the bathymetrical shift ofZoophycosfrom the littoral–neritic to bathyal environments is synchronized with the tiering shift from shallow to deep. By detailed comparison with body fossils, geochemical and palaeogeographical records, we conclude that the macroevolution of PhanerozoicZoophycosis multi-affected by the global biodiversity expansion, benthic nutrient enhancement and the biotic macroevolution of theZoophycos-producers. The macroevolution of development evidenced by the morphological changes ofZoophycosand other trace fossils, may have great implications on the behavioural and physiological adaptation of ancient animals to the environments.
Large-Scale Molecular Simulations on the Mechanical Response and Failure Behavior of a defective Graphene: Cases of 5–8–5 Defects
Authors: Wang Shuaiwei , Yang Baocheng , Yuan Jinyun , Si Yubing , Chen Houyang 
Published: October 2015

AbstractUnderstanding the effect of defects on mechanical responses and failure behaviors of a graphene membrane is important for its applications. As examples, in this paper, a family of graphene with various 5–8–5 defects are designed and their mechanical responses are investigated by employing molecular dynamics simulations. The dependence of fracture strength and strain as well as Young’s moduli on the nearest neighbor distance and defect types is examined. By introducing the 5–8–5 defects into graphene, the fracture strength and strain become smaller. However, the Young’s moduli of DL (Linear arrangement of repeat unit 5–8–5 defect along zigzag-direction of graphene), DS (a Slope angle between repeat unit 5–8–5 defect and zigzag direction of graphene) and DZ (Zigzag-like 5–8–5 defects) defects in the zigzag direction become larger than those in the pristine graphene in the same direction. A maximum increase of 11.8% of Young’s modulus is obtained. Furthermore, the brittle cracking mechanism is proposed for the graphene with 5–8–5 defects. The present work may provide insights in controlling the mechanical properties by preparing defects in the graphene and give a full picture for the applications of graphene with defects in flexible electronics and nanodevices.
Despair-associated memory requires a slow-onset CA1 long-term potentiation with unique underlying mechanisms
Authors: Jing Liang , Duan Ting-Ting , Tian Meng , Yuan Qiang , Tan Ji-Wei , Zhu Yong-Yong , Ding Ze-Yang , Cao Jun , Yang Yue-Xiong , Zhang Xia , Mao Rong-Rong , Richter-levin Gal , Zhou Qi-Xin , Xu Lin 
Published: October 2015

AbstractThe emotion of despair that occurs with uncontrollable stressful event is probably retained by memory, termed despair-associated memory, although little is known about the underlying mechanisms. Here, we report that forced swimming (FS) with no hope to escape, but not hopefully escapable swimming (ES), enhances hippocampal α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-dependent GluA1 Ser831 phosphorylation (S831-P), induces a slow-onset CA1 long-term potentiation (LTP) in freely moving rats and leads to increased test immobility 24-h later. Before FS application of the antagonists to block S831-P or N-methyl-D-aspartic acid receptor (NMDAR) or glucocorticoid receptor (GR) disrupts LTP and reduces test immobility, to levels similar to those of the ES group. Because these mechanisms are specifically linked with the hopeless of escape from FS, we suggest that despair-associated memory occurs with an endogenous CA1 LTP that is intriguingly mediated by a unique combination of rapid S831-P with NMDAR and GR activation to shape subsequent behavioral despair.
Maternal intraguild predation risk affects offspring anti-predator behavior and learning in mites
Authors: Seiter Michael , Schausberger Peter 
Published: October 2015

AbstractPredation risk is a strong selective force shaping prey morphology, life history and behavior. Anti-predator behaviors may be innate, learned or both but little is known about the transgenerational behavioral effects of maternally experienced predation risk. We examined intraguild predation (IGP) risk-induced maternal effects on offspring anti-predator behavior, including learning, in the predatory mite Phytoseiulus persimilis. We exposed predatory mite mothers during egg production to presence or absence of the IG predator Amblyseius andersoni and assessed whether maternal stress affects the anti-predator behavior, including larval learning ability, of their offspring as protonymphs. Protonymphs emerging from stressed or unstressed mothers and having experienced IGP risk as larvae or not, were subjected to choice situations with and without IG predator traces. Predator-experienced protonymphs from stressed mothers were the least active and acted the boldest in site choice towards predator cues. We argue that the attenuated response of the protonymphs to predator traces alone represents optimized risk management because no immediate risk existed. Such behavioral adjustment could reduce the inherent fitness costs of anti-predator behaviors. Overall, our study suggests that P. persimilis mothers experiencing IGP risk may prime their offspring to behave more optimally in IGP environments.
Rpn10 monoubiquitination orchestrates the association of the ubiquilin-type DSK2 receptor with the proteasome
Authors: Zuin Alice , Bichmann Anne , Isasa Marta , Puig-Sàrries Pilar , Díaz Luís Miguel , Crosas Bernat 
Published: October 2015

Despite the progress made in understanding the roles of proteasome polyubiquitin receptors, such as the subunits Rpn10 (regulatory particle non-ATPase 10) and Rpn13, and the transient interactors Rad23 (radiation sensitivity abnormal 23) and Dsk2 (dual-specificity protein kinase 2), the mechanisms involved in their regulation are virtually unknown. Rpn10, which is found in the cell in proteasome-bound and -unbound pools, interacts with Dsk2, and this interaction has been proposed to regulate the amount of Dsk2 that gains access to the proteasome. Rpn10 monoubiquitination has emerged as a conserved mechanism with a strong effect on Rpn10 function. In the present study, we show that functional yeast proteasomes have the capacity to associate and dissociate with Rpn10 and that Rpn10 monoubiquitination decreases the Rpn10–proteasome and Rpn10–Dsk2 associations. Remarkably, this process facilitates the formation of Dsk2–proteasomes in vivo. Therefore, Rpn10 monoubiquitination acts as mechanism that serves to switch the proteasome from an ‘Rpn10 high/Dsk2 low’ state to an ‘Rpn10 low/Dsk2 high’ state. Interestingly, Rpn10–ubiquitin, with an inactivated ubiquitin-interacting motif (UIM), and Dsk2I45S, with an inactive ubiquitin-like domain (UBL), show temperature-dependent phenotypes with multiple functional interactions.