bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stanniocalcin-2 contributes to mesenchymal stromal cells attenuating murine contact hypersensitivity mainly via reducing CD8+ Tc1 cells
Authors: Chen Xiaoyong , Liu Qiuli , Huang Weijun , Cai Chuang , Xia Wenjie , Peng Yanwen , Zheng Shuwei , Li Gang , Xu Yan , Wang Jiancheng , Liu Chang , Zhang Xiaoran , Huang Li , Xiang Andy Peng , Zhang Qi 
Published: May 2018

AbstractMesenchymal stromal cells (MSCs) have been demonstrated to ameliorate allergic contact dermatitis (ACD), a typical T-cell-mediated disorder. However, the underlying mechanisms behind the MSC-based treatment for ACD have not yet been fully elucidated. The stanniocalcins (STCs) comprise a family of secreted glycoprotein hormones that act as important anti-inflammatory proteins. Here, we investigated the roles of STCs in MSC-mediated T-cell suppression and their potential role in the MSC-based treatment for ACD. Gene expression profiling revealed that STC2, but not STC1, was highly expressed in MSCs. STC2 knockdown in MSCs significantly impaired their effects in reducing TNF-α- and IFN-γ-producing CD8+T cells. Importantly, silencing the STC2 expression in MSCs abated their therapeutic effect on contact hypersensitivity (CHS) in mice, mainly restoring the generation and infiltration of IFN-γ-producing CD8+T cells (Tc1 cells). Mechanistically, STC2 co-localized with heme oxygenase 1 (HO-1) in MSCs, and contributed to MSC-mediated reduction of CD8+Tc1 cells via regulating HO-1 activity. Together, these findings newly identify STC2 as the first stanniocalcin responsible for mediating the immunomodulatory effects of MSCs on allogeneic T cells and STC2 contribute to MSC-based treatment for ACD mainly via reducing the CD8+Tc1 cells.
Simulated microgravity induces a cellular regression of the mature phenotype in human primary osteoblasts
Authors: Gioia Magda , Michaletti Anna , Scimeca Manuel , Marini Mario , Tarantino Umberto , Zolla Lello , Coletta Massimo 
Published: May 2018

AbstractDecreased mechanical loading on bones, such as prolonged bed rest and microgravity during space flights, leads to the development of an osteoporotic-like phenotype. Although osteoblast hypo-functionality is reported to be involved in the progression of bone pathological conditions, the cellular mechanisms of this process remain largely unknown. The combined application of mass spectrometry “–omics” and histochemical and ultrastructural approaches have been employed to investigate the effects of the gravitational unloading on human bone-cell biology. Here we show, ex vivo, that simulated microgravity (Sμg) on human primary osteoblasts (hpOB) induces an alteration of pro-osteogenic determinants (i.e., cell morphology and deposit of hydroxyapatite crystals), accompanied by a downregulation of adhesive proteins and bone differentiation markers (e.g., integrin beta-1, protein folding Crystallin Alpha B (CRYα-B), runt-related transcription factor 2 (RUNX-2), bone morphogenic protein-2 (BMP-2), and receptor activator of nuclear factor kappa-B ligand (RANK-L)), indicating an impairment of osteogenesis. Further, we observed for the first time that Sμg can trigger a transition toward a mesenchymal-like phenotype, in which a mature osteoblast displays an hampered vitamin A metabolism, loses adhesive molecules, gains mesenchymal components (e.g., pre-osteoblast state marker CD44), morphological protrusions (filopodium-like), enhances GTPase activities, which in turn allows it to acquire migrating properties. Although this phenotypic conversion is not complete and can be reversible, Sμg environment proves a plasticity potential hidden on Earth. Overall, our results suggest that Sμg can be a powerful physical cue for triggering ex vivo a dedifferentiation impulse on hpOBs, opening a new scenario of possible innovative therapeutical biomechanical strategies for the treatment of osteo-degenerative diseases.
The p53 activator overcomes resistance to ALK inhibitors by regulating p53-target selectivity in ALK-driven neuroblastomas
Authors: Miyazaki Makoto , Otomo Ryo , Matsushima-Hibiya Yuko , Suzuki Hidenobu , Nakajima Ayana , Abe Naomi , Tomiyama Arata , Ichimura Koichi , Matsuda Koichi , Watanabe Toshiki , Ochiya Takahiro , Nakagama Hitoshi , Sakai Ryuichi , Enari Masato 
Published: May 2018

AbstractAnaplastic lymphoma kinase (ALK) is an oncogenic receptor tyrosine kinase that is activated by gene amplification and mutation in neuroblastomas. ALK inhibitors can delay the progression of ALK-driven cancers, but are of limited use owing to ALK inhibitor resistance. Here, we show that resistance to ALK inhibitor in ALK-driven neuroblastomas can be attenuated by combination treatment with a p53 activator. Either ALK inhibition or p53 activator treatment induced cell cycle arrest, whereas combination treatment induced apoptosis, and prevented tumour relapse both in vitro and in vivo. This shift toward apoptosis, and away from cell-cycle arrest, in the presence of an ALK inhibitor and a p53 activator, is mediated by inhibition of the ALK–AKT–FOXO3a axis leading to a specific upregulation of SOX4. SOX4 cooperates with p53 to upregulate the pro-apoptotic protein PUMA. These data therefore suggest a novel combination therapy strategy for treating ALK-driven neuroblastomas.
Identifying and characterizing SCRaMbLEd synthetic yeast using ReSCuES
Authors: Luo Zhouqing , Wang Lihui , Wang Yun , Zhang Weimin , Guo Yakun , Shen Yue , Jiang Linghuo , Wu Qingyu , Zhang Chong , Cai Yizhi , Dai Junbiao 
Published: May 2018

AbstractSCRaMbLE is a novel system implemented in the synthetic yeast genome, enabling massive chromosome rearrangements to produce strains with a large genotypic diversity upon induction. Here we describe a reporter of SCRaMbLEd cells using efficient selection, termed ReSCuES, based on a loxP-mediated switch of two auxotrophic markers. We show that all randomly isolated clones contained rearrangements within the synthetic chromosome, demonstrating high efficiency of selection. Using ReSCuES, we illustrate the ability of SCRaMbLE to generate strains with increased tolerance to several stress factors, such as ethanol, heat and acetic acid. Furthermore, by analyzing the tolerant strains, we are able to identify ACE2, a transcription factor required for septum destruction after cytokinesis, as a negative regulator of ethanol tolerance. Collectively, this work not only establishes a generic platform to rapidly identify strains of interest by SCRaMbLE, but also provides methods to dissect the underlying mechanisms of resistance.
Rapid host strain improvement by in vivo rearrangement of a synthetic yeast chromosome
Authors: Blount B. A. , Gowers G-O. F. , Ho J. C. H. , Ledesma-Amaro R. , Jovicevic D. , McKiernan R. M. , Xie Z. X. , Li B. Z. , Yuan Y. J. , Ellis T. 
Published: May 2018

AbstractSynthetic biology tools, such as modular parts and combinatorial DNA assembly, are routinely used to optimise the productivity of heterologous metabolic pathways for biosynthesis or substrate utilisation, yet it is well established that host strain background is just as important for determining productivity. Here we report that in vivo combinatorial genomic rearrangement of Saccharomyces cerevisiae yeast with a synthetic chromosome V can rapidly generate new, improved host strains with genetic backgrounds favourable to diverse heterologous pathways, including those for violacein and penicillin biosynthesis and for xylose utilisation. We show how the modular rearrangement of synthetic chromosomes by SCRaMbLE can be easily determined using long-read nanopore sequencing and we explore experimental conditions that optimise diversification and screening. This synthetic genome approach to metabolic engineering provides productivity improvements in a fast, simple and accessible way, making it a valuable addition to existing strain improvement techniques.
Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system
Authors: Ramírez Julia , Duijvenboden Stefan van , Ntalla Ioanna , Mifsud Borbala , Warren Helen R , Tzanis Evan , Orini Michele , Tinker Andrew , Lambiase Pier D. , Munroe Patricia B. 
Published: May 2018

AbstractImpaired capacity to increase heart rate (HR) during exercise (ΔHRex), and a reduced rate of recovery post-exercise (ΔHRrec) are associated with higher cardiovascular mortality rates. Currently, the genetic basis of both phenotypes remains to be elucidated. We conduct genome-wide association studies (GWASs) for ΔHRex and ΔHRrec in ~40,000 individuals, followed by replication in ~27,000 independent samples, all from UK Biobank. Six and seven single-nucleotide polymorphisms for ΔHRex and ΔHRrec, respectively, formally replicate. In a full data set GWAS, eight further loci for ΔHRex and nine for ΔHRrec are genome-wide significant (P ≤ 5 × 10−8). In total, 30 loci are discovered, 8 being common across traits. Processes of neural development and modulation of adrenergic activity by the autonomic nervous system are enriched in these results. Our findings reinforce current understanding of HR response to exercise and recovery and could guide future studies evaluating its contribution to cardiovascular risk prediction.
Molecular solar thermal energy storage in photoswitch oligomers increases energy densities and storage times
Authors: Mansø Mads , Petersen Anne Ugleholdt , Wang Zhihang , Erhart Paul , Nielsen Mogens Brøndsted , Moth-Poulsen Kasper 
Published: May 2018

AbstractMolecular photoswitches can be used for solar thermal energy storage by photoisomerization into high-energy, meta-stable isomers; we present a molecular design strategy leading to photoswitches with high energy densities and long storage times. High measured energy densities of up to 559 kJ kg−1 (155 Wh kg−1), long storage lifetimes up to 48.5 days, and high quantum yields of conversion of up to 94% per subunit are demonstrated in norbornadiene/quadricyclane (NBD/QC) photo-/thermoswitch couples incorporated into dimeric and trimeric structures. By changing the linker unit between the NBD units, we can at the same time fine-tune light-harvesting and energy densities of the dimers and trimers so that they exceed those of their monomeric analogs. These new oligomers thereby meet several of the criteria to be met for an optimum molecule to ultimately enter actual devices being able to undergo closed cycles of solar light-harvesting, energy storage, and heat release.
Rapid pathway prototyping and engineering using in vitro and in vivo synthetic genome SCRaMbLE-in methods
Authors: Liu Wei , Luo Zhouqing , Wang Yun , Pham Nhan T. , Tuck Laura , Pérez-Pi Irene , Liu Longying , Shen Yue , French Chris , Auer Manfred , Marles-Wright Jon , Dai Junbiao , Cai Yizhi 
Published: May 2018

AbstractExogenous pathway optimization and chassis engineering are two crucial methods for heterologous pathway expression. The two methods are normally carried out step-wise and in a trial-and-error manner. Here we report a recombinase-based combinatorial method (termed “SCRaMbLE-in”) to tackle both challenges simultaneously. SCRaMbLE-in includes an in vitro recombinase toolkit to rapidly prototype and diversify gene expression at the pathway level and an in vivo genome reshuffling system to integrate assembled pathways into the synthetic yeast genome while combinatorially causing massive genome rearrangements in the host chassis. A set of loxP mutant pairs was identified to maximize the efficiency of the in vitro diversification. Exemplar pathways of β-carotene and violacein were successfully assembled, diversified, and integrated using this SCRaMbLE-in method. High-throughput sequencing was performed on selected engineered strains to reveal the resulting genotype-to-phenotype relationships. The SCRaMbLE-in method proves to be a rapid, efficient, and universal method to fast track the cycle of engineering biology.
Asynchronous suppression of visual cortex during absence seizures in stargazer mice
Authors: Meyer Jochen , Maheshwari Atul , Noebels Jeffrey , Smirnakis Stelios 
Published: May 2018

AbstractAbsence epilepsy is a common childhood disorder featuring frequent cortical spike-wave seizures with a loss of awareness and behavior. Using the calcium indicator GCaMP6 with in vivo 2-photon cellular microscopy and simultaneous electrocorticography, we examined the collective activity profiles of individual neurons and surrounding neuropil across all layers in V1 during spike-wave seizure activity over prolonged periods in stargazer mice. We show that most (~80%) neurons in all cortical layers reduce their activity during seizures, whereas a smaller pool activates or remains neutral. Unexpectedly, ictal participation of identified single-unit activity is not fixed, but fluctuates on a flexible time scale from seizure to seizure. Pairwise correlation analysis of calcium activity reveals a surprising lack of synchrony among neurons and neuropil patches in all layers during seizures. Our results demonstrate asynchronous suppression of visual cortex during absence seizures, with potential implications for understanding cortical network function during EEG states of reduced awareness.
Effect of ionic composition on thermal properties of energetic ionic liquids
Authors: Park Chihyun , Han Minsu , Kim Jinbo , Lee Woojae , Kim Eunkyoung 
Published: May 2018

AbstractA model to predict the effect of ionic composition on the thermal properties of energetic ionic liquids was developed by quantitative structure-property relationship modeling, which predicted the detonation velocity, pressure, and melting temperature of energetic ionic liquids. A hybrid approach was used to determine the optimal subset of descriptors by combining regression with the genetic algorithm as an optimization method. The model showed the high accuracy, reaching a correlation factor of R2 as 0.71, 0.73 and 0.68 for the correlation between the calculated detonation velocity, pressure and melting temperature against reported values. It was validated extensively and compared to the Kamlet–Jacobs equation. The effect of ion composition on the thermal properties of energetic ionic liquids could be quantitatively analyzed through the developed model, to give an insight for the design of new energetic ionic liquids.
Slow touch targeting CT-fibres does not increase prosocial behaviour in economic laboratory tasks
Authors: Rosenberger Lisa Anna , Ree Anbjørn , Eisenegger Christoph , Sailer Uta 
Published: May 2018

AbstractField studies have demonstrated that humans become more generous, helpful and compliant after having been touched by another person. Here, we explored whether these effects are larger for touch activating the C-tactile (CT) fibres, as it is ascribed a particular role in establishing and maintaining bonds and affiliative interactions. The role of CT-targeted and non-targeted touch on prosocial behaviour was investigated in three different experiments using a trust game and a task measuring individual differences in social value orientations (the SVO task). Whereas participants in general acted prosocially, there was no influence of CT-targeted touch on prosocial behaviour, both in comparison to non-CT-targeted control touch and visual (non-tactile) stimulation. The null findings were further corroborated by Bayesian statistics. Thus, under the controlled laboratory conditions employed, CT-targeted touch did not play a particular role in prosocial behaviour. This indicates that touch does not increase prosocial behaviour in the absence of meaningful social and psychological connotations. Any touch related effects on prosocial behaviour likely depends on the ecological validity of the situation.
Effectiveness of in-Line Filters to Completely Remove Particulate Contamination During a Pediatric Multidrug Infusion Protocol
Authors: Perez Maxime , Décaudin Bertrand , Abou Chahla Wadih , Nelken Brigitte , Storme Laurent , Masse Morgane , Barthélémy Christine , Lebuffe Gilles , Odou Pascal 
Published: May 2018

AbstractThe large number of drugs administered simultaneously to neonates and children in hospital results in the formation of particles that are potentially infused. We have investigated the ability of IV in-line filters to eliminate particulate matter from multidrug infusion lines and so prevent contamination. The impact on particle occurrence of the internal volume of the IV line below the in-line filter was then evaluated. The multidrug therapy given to children was reproduced with and without in-line filtration. Three combinations with a filter were tested to vary the internal volume (V) between the filter and the catheter egress. The catheter was then connected to a dynamic particle count to evaluate the particulate matter potentially administered to children during infusion. The introduction of in-line filters led to a significant reduction in overall particulate matter, from 416,974 [208,479–880,229] to 7,551 [1,985–11,287] particles (p < 0.001). Larger particles of ≥10 and 25 µm were also significantly reduced. Adding an extension set to the egress of the in-line filter (V = 1.7 mL) caused a significant increase in particulate contamination for both. This study showed that in-line filtration is an effective tool in preventing particle administration to patients. Their position in the infusion in-line is therefore important because of its impact on internal volume and drug particle formation.
Cattle with a precise, zygote-mediated deletion safely eliminate the major milk allergen beta-lactoglobulin
Authors: Wei Jingwei , Wagner Stefan , Maclean Paul , Brophy Brigid , Cole Sally , Smolenski Grant , Carlson Dan F. , Fahrenkrug Scott C. , Wells David N. , Laible Götz 
Published: May 2018

AbstractWe applied precise zygote-mediated genome editing to eliminate beta-lactoglobulin (BLG), a major allergen in cows’ milk. To efficiently generate LGB knockout cows, biopsied embryos were screened to transfer only appropriately modified embryos. Transfer of 13 pre-selected embryos into surrogate cows resulted in the birth of three calves, one dying shortly after birth. Deep sequencing results confirmed conversion of the genotype from wild type to the edited nine bp deletion by more than 97% in the two male calves. The third calf, a healthy female, had in addition to the expected nine bp deletion (81%), alleles with an in frame 21 bp deletion (<17%) at the target site. While her milk was free of any mature BLG, we detected low levels of a BLG variant derived from the minor deletion allele. This confirmed that the nine bp deletion genotype completely knocks out production of BLG. In addition, we showed that the LGB knockout animals are free of any TALEN-mediated off-target mutations or vector integration events using an unbiased whole genome analysis. Our study demonstrates the feasibility of generating precisely biallelically edited cattle by zygote-mediated editing for the safe production of hypoallergenic milk.
Short-term temporal memory in idiopathic and Parkin-associated Parkinson’s disease
Authors: Degos Bertrand , Ameqrane Ilhame , Rivaud-Péchoux Sophie , Pouget Pierre , Missal Marcus 
Published: May 2018

AbstractIn a rapidly changing environment, we often know when to do something before we have to do it. This preparation in the temporal domain is based on a ‘perception’ of elapsed time and short-term memory of previous stimulation in a similar context. These functions could be perturbed in Parkinson’s disease. Therefore, we investigated their role in eye movement preparation in sporadic Parkinson’s disease and in a very infrequent variant affecting the Parkin gene. We used a simple oculomotor task where subjects had to orient to a visual target and movement latency was measured. We found that in spite of an increased average reaction time, the influence of elapsed time on movement preparation was similar in controls and the two groups of PD patients. However, short-term temporal memory of previous stimulation was severely affected in sporadic PD patients either ON or OFF dopaminergic therapy. We conclude that the two different contributions to temporal preparation could be dissociated. Moreover, a short-term temporal memory deficit might underlie temporal cognition deficits previously observed in PD.
Yttrium (III) Recovery with D2EHPA in Pseudo-Emulsion Hollow Fiber Strip Dispersion System
Authors: Pirom Teerapon , Arponwichanop Amornchai , Pancharoen Ura , Yonezawa Tetsu , Kheawhom Soorathep 
Published: May 2018

AbstractYttrium (Y) is an essential lanthanide rare earth element and can be effectively extracted and purified using a hollow fiber supported liquid membrane (HFSLM) system. However, the stability of HFSLM system is a significant challenge. Pseudoemulsion-hollow fiber strip dispersion (PEHFSD) system, providing excellent stability, is attracting research attention. In this work, the recovery of Y(III) by PEHFSD system using di(2-ethylhexyl)phosphoric acid (D2EHPA) as a carrier was investigated. The effects of several operating parameters, including the initial concentration of Y(III) in the feed phase, the flow rate of feed, the stirring speed and the volumetric ratio of feed to strip on Y(III) separation were studied. The Y(III) transport was analyzed on the concentration ratio of Y(III) ions, percent extraction, percent stripping and overall mass transfer coefficient (K
p
). The PEHFSD system outperformed HFSLM system regarding separation performance and stability. K
p
of HFSLM system decreased after the second run, but K
p
of PEHFSD system remained constant even at the fifth run. The dispersed droplets in the strip dispersion phase in the PEHFSD system enhanced separation performance and stability of the membrane module.
Common drivers of seasonal movements on the migration – residency behavior continuum in a large herbivore
Authors: Martin Jodie , Tolon Vincent , Morellet Nicolas , Santin-Janin Hugues , Licoppe Alain , Fischer Claude , Bombois Jérôme , Patthey Patrick , Pesenti Elias , Chenesseau Delphine , Saïd Sonia 
Published: May 2018

AbstractThis study aimed to (1) identify the scale of environmental drivers of seasonal movements on the migration – residency behavior continuum in a large herbivore species and to (2) test the hypothesis that the same environmental drivers and spatio-temporal scaling should influence spatial processes in both migrants (long distance migration) and residents (short distance range shifts). We performed a comparative analysis of the influence of plant phenology and snow cover duration on seasonal movements of five partially migrating red deer populations with contrasting environmental conditions, at the seasonal range scale and at the study area scale. The five populations presented varying proportions of migrants, large gradients of migration distances and seasonal range shifts. The probability for a red deer to migrate was strongly influenced by large-scale environmental conditions, consistent with the resource heterogeneity hypothesis (high spatio-temporal scaling favors migration). Distances moved by both migrants and residents were strongly related to large-scale environmental conditions as well. We showed that similar proximal causes influenced these seasonal movements, reinforcing the idea of a continuum from migration to residency in response to seasonal environmental changes. Together, our findings suggest that global warming, by homogenizing large-scale environmental conditions, may thus decrease migratory tactics.