bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel phosphorylation by AMP-activated kinase regulates RUNX2 from ubiquitination in osteogenesis over adipogenesis
Authors: Chava Suresh , Chennakesavulu S. , Gayatri B. Meher , Reddy Aramati B. M. 
Published: July 2018

AbstractMesenchymal stem cells (MSCs) function as progenitors to a variety of cell types. The reported association between osteogenic and adipogenic commitment during differentiation is due to the regulation of key transcription factors in the signaling pathways. However, the process of adipogenesis at the expense of osteogenic phenotype during metabolic stress is still unclear. In this study, we showed for the first time that RUNX2 is a novel substrate of AMP-activated kinase (AMPK), which directly phosphorylates at serine 118 residue in the DNA-binding domain of RUNX2. Our results in in vitro MSC lineage differentiation models confirmed that active AMPK and RUNX2-S118 phosphorylation are preferentially associated with osteogenic commitment, whereas the lack of this phosphorylation leads to adipogenesis. This interplay is regulated by the ubiquitination of non-phosphorylated RUNX2-S118, which is evident in the dominant mutant RUNX2-S118D. Pharmacological activation of AMPK by metformin significantly abrogated the loss of RUNX2-S118 phosphorylation and protected from tunicamycin-induced endoplasmic reticulum stress, high glucose-induced in vitro adipogenesis and streptozotocin-induced in vivo bone adiposity and bone phenotype. In conclusion, results from this study demonstrated that RUNX2 is a direct target of AMPK which simplified the outlook towards several complex mechanisms that are currently established concerning cellular metabolism and pathogenesis.
Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells
Authors: Pakravan Golnaz , Foroughmand Ali Mohammad , Peymani Maryam , Ghaedi Kamran , Hashemi Motahare-Sadat , Hajjari Mohammadreza , Nasr-Esfahani Mohammad Hossein 
Published: July 2018

AbstractDoxorubicin (Dox) is a widely used powerful chemotherapeutic component for cancer treatment. However, its clinical application has been hampered due to doxorubicin-induced cardiomyopathy upon the cessation of chemotherapy. Previous studies revealed that PPARγ plays a crucial protective role in cardiomyocytes. Modulation of miRNA expression is an applicable approach for prohibition of toxicity induction. Therefore, the aim of present study is uprising of PPARγ transcript levels via manipulation of miRNAs to limit Dox-induced cardiotoxicity in mESCs-derived cardiac cells, as in vitro model cell to provide a simple direct approach for further clinical therapies. Based on bioinformatics data mining, eventually miR-130a was selected to target PPARγ. This miRNA is highly expressed in heart. The expression of miR-130a increases sharply upon Dox treatment while specific antagomiR-130a reverses Dox-induced reduced expression of PPARγ, cellular apoptosis, and inflammation. Our data strongly suggest that antagomiR-130a limits Dox-induced cellular toxicity via PPARγ upregulation and may have clinical relevance to limit in vivo Dox toxicity.
Nicotine aversion is mediated by GABAergic interpeduncular nucleus inputs to laterodorsal tegmentum
Authors: Wolfman Shannon L. , Gill Daniel F. , Bogdanic Fili , Long Katie , Al-Hasani Ream , McCall Jordan G. , Bruchas Michael R. , McGehee Daniel S. 
Published: July 2018

AbstractNicotine use can lead to dependence through complex processes that are regulated by both its rewarding and aversive effects. Recent studies show that aversive nicotine doses activate excitatory inputs to the interpeduncular nucleus (IPN) from the medial habenula (MHb), but the downstream targets of the IPN that mediate aversion are unknown. Here we show that IPN projections to the laterodorsal tegmentum (LDTg) are GABAergic using optogenetics in tissue slices from mouse brain. Selective stimulation of these IPN axon terminals in LDTg in vivo elicits avoidance behavior, suggesting that these projections contribute to aversion. Nicotine modulates these synapses in a concentration-dependent manner, with strong enhancement only seen at higher concentrations that elicit aversive responses in behavioral tests. Optogenetic inhibition of the IPN–LDTg connection blocks nicotine conditioned place aversion, suggesting that the IPN–LDTg connection is a critical part of the circuitry that mediates the aversive effects of nicotine.
Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection
Authors: Baeza Garcia Alvaro , Siu Edwin , Sun Tiffany , Exler Valerie , Brito Luis , Hekele Armin , Otten Gib , Augustijn Kevin , Janse Chris J. , Ulmer Jeffrey B. , Bernhagen Jürgen , Fikrig Erol , Geall Andrew , Bucala Richard 
Published: July 2018

AbstractPlasmodium species produce an ortholog of the cytokine macrophage migration inhibitory factor, PMIF, which modulates the host inflammatory response to malaria. Using a novel RNA replicon-based vaccine, we show the impact of PMIF immunoneutralization on the host response and observed improved control of liver and blood-stage Plasmodium infection, and complete protection from re-infection. Vaccination against PMIF delayed blood-stage patency after sporozoite infection, reduced the expression of the Th1-associated inflammatory markers TNF-α, IL-12, and IFN-γ during blood-stage infection, augmented Tfh cell and germinal center responses, increased anti-Plasmodium antibody titers, and enhanced the differentiation of antigen-experienced memory CD4 T cells and liver-resident CD8 T cells. Protection from re-infection was recapitulated by the adoptive transfer of CD8 or CD4 T cells from PMIF RNA immunized hosts. Parasite MIF inhibition may be a useful approach to promote immunity to Plasmodium and potentially other parasite genera that produce MIF orthologous proteins.
Strong plates enhance mantle mixing in early Earth
Authors: Agrusta Roberto , van Hunen Jeroen , Goes Saskia 
Published: July 2018

AbstractIn the present-day Earth, some subducting plates (slabs) are flattening above the upper–lower mantle boundary at ~670 km depth, whereas others go through, indicating a mode between layered and whole-mantle convection. Previous models predicted that in a few hundred degree hotter early Earth, convection was likely more layered due to dominant slab stagnation. In self-consistent numerical models where slabs have a plate-like rheology, strong slabs and mobile plate boundaries favour stagnation for old and penetration for young slabs, as observed today. Here we show that such models predict slabs would have penetrated into the lower mantle more easily in a hotter Earth, when a weaker asthenosphere and decreased plate density and strength resulted in subduction almost without trench retreat. Thus, heat and material transport in the Earth’s mantle was more (rather than less) efficient in the past, which better matches the thermal evolution of the Earth.
Nonstimulatory peptide–MHC enhances human T-cell antigen-specific responses by amplifying proximal TCR signaling
Authors: Zhao Xiang , Sankaran Shvetha , Yap Jiawei , Too Chien Tei , Ho Zi Zong , Dolton Garry , Legut Mateusz , Ren Ee Chee , Sewell Andrew K. , Bertoletti Antonio , MacAry Paul A. , Brzostek Joanna , Gascoigne Nicholas R. J. 
Published: July 2018

AbstractForeign antigens are presented by antigen-presenting cells in the presence of abundant endogenous peptides that are nonstimulatory to the T cell. In mouse T cells, endogenous, nonstimulatory peptides have been shown to enhance responses to specific peptide antigens, a phenomenon termed coagonism. However, whether coagonism also occurs in human T cells is unclear, and the molecular mechanism of coagonism is still under debate since CD4 and CD8 coagonism requires different interactions. Here we show that the nonstimulatory, HIV-derived peptide GAG enhances a specific human cytotoxic T lymphocyte response to HBV-derived epitopes presented by HLA-A*02:01. Coagonism in human T cells requires the CD8 coreceptor, but not T-cell receptor (TCR) binding to the nonstimulatory peptide–MHC. Coagonists enhance the phosphorylation and recruitment of several molecules involved in the TCR-proximal signaling pathway, suggesting that coagonists promote T-cell responses to antigenic pMHC by amplifying TCR-proximal signaling.
Perspective: bidirectional exosomal transport between cancer stem cells and their fibroblast-rich microenvironment during metastasis formation
Authors: Valcz Gábor , Buzás Edit Irén , Szállási Zoltán , Kalmár Alexandra , Krenács Tibor , Tulassay Zsolt , Igaz Péter , Molnár Béla 
Published: July 2018

AbstractCarcinomas are complex structures composed of hierarchically organized distinct cell populations such as cancer stem cells and non-stem (bulk) cancer cells. Their genetic/epigenetic makeup and the dynamic interplay between the malignant cell populations and their stromal fibroblasts are important determinants of metastatic tumor invasion. Important mediators of these interactions are the small, membrane-enclosed extracellular vesicles, in particular exosomes. Both cancer cell and fibroblast-derived exosomes carry a set of regulatory molecules, including proteins and different species of RNA, which cooperatively support metastatic tumor spread. Here, we briefly overview potential links between cancer stem cells and the exosome-mediated fibroblast-enriched metastatic niche formation to discuss their role in the promotion of tumor growth and metastatic expansion in breast carcinoma models.
Revealing the complex genetic structure of cultivated amaryllis (Hippeastrum hybridum) using transcriptome-derived microsatellite markers
Authors: Wang Yi , Chen Defeng , He Xiaofeng , Shen Jiangxian , Xiong Min , Wang Xian , Zhou Di , Wei Zunzheng 
Published: July 2018

AbstractAlthough amaryllis (Hippeastrum hybridum) plants are commonly used in physiological and ecological research, the extent of their genomic and genetic resources remains limited. The development of molecular markers is therefore of great importance to accelerate genetic improvements in Hippeastrum species. In this study, a total of 269 unique genes were defined that might regulate the flower spathe development of amaryllis. In addition, 2000 simple sequence repeats (SSRs) were detected based on 171,462 de novo assembled unigenes from transcriptome data, and 66,4091 single nucleotide polymorphisms (SNPs) were also detected as putative molecular markers. Twenty-one SSR markers were screened to evaluate the genetic diversity and population structure of 104 amaryllis accessions. A total of 98 SSR loci were amplified for all accessions. The results reveal that Nei’s gene diversity (H) values of these markers ranged between 0.055 and 0.394, whereas the average values of Shannon’s Information index (I) ranged between 0.172 and 0.567. Genetic tree analysis further demonstrates that all accessions can be grouped into three main clusters, which can be further divided into two subgroups. STRUCTURE-based analysis revealed that the highest ΔK values were observed when K = 5, K = 6, K = 7 and K = 8. The results of this study enable large-scale transcriptomics and classification of Hippeastrum genetic polymorphisms and will be useful in the future for resource conservation and production.
Improving the efficiency of rear emitter silicon solar cell using an optimized n-type silicon oxide front surface field layer
Authors: Kim Sangho , Park Jinjoo , Phong Pham Duy , Shin Chonghoon , Iftiquar S. M. , Yi Junsin 
Published: July 2018

AbstractOptical and electrical characteristics of n-type nano-crystalline-silicon oxide (n-µc-SiO:H) materials can be varied to optimize and improve the performance of a solar cell. In silicon heretojunction (SHJ) solar cells, it can be used to improve carrier selectivity and optical transmission at the front side, both of which are vitally important in device operation. For this purpose, the n-µc-SiO:H was investigated as the front surface field (FSF) layer. During film deposition, an increased CO2 flow rate from 0 to 6 sccm resulted in changes of crystalline volume fractions from 57 to 28%, optical band-gaps from 1.98 to 2.21 eV, dark conductivities from 7.29 to 1.1 × 10−5 S/cm, and activation energies from 0.019 to 0.29 eV, respectively. In device applications, a minimum optical reflection was estimated for the FSF layer that was fabricated with 4 sccm CO2 (FSF-4), and therefore obtained the highest external quantum efficiency, although short circuit current density (Jsc) was 38.83 mA/cm2 and power conversion efficiency (PCE) was 21.64%. However, the highest PCE of 22.34% with Jsc = 38.71 mA/cm2 was observed with the FSF prepared with 2 sccm CO2 (FSF-2), as the combined opto-electronic properties of FSF-2 were better than those of the FSF-4.
Quantum Zeno Effect assisted Spectroscopy of a single trapped Ion
Authors: Ozawa Akira , Davila-Rodriguez Josue , Hänsch Theodor W. , Udem Thomas 
Published: July 2018

AbstractThe quantum Zeno effect (QZE) is not only interesting as a manifestation of the counterintuitive behavior of quantum mechanics, but may also have practical applications. When a spectroscopy laser is applied to target atoms or ions prepared in an initial state, the Rabi flopping of an auxiliary transition sharing one common level can be inhibited. This effect is found to be strongly dependent on the detuning of the spectroscopy laser and offers a sensitive spectroscopy signal which allows for high precision spectroscopy of transitions with a small excitation rate. We demonstrate this method with direct frequency comb spectroscopy using the minute power of a single mode to drive a dipole allowed transition in a single trapped ion. Resolving the individual modes of the frequency comb demonstrates that the simple instantaneous quantum collapse description of the QZE can not be applied here, as these modes need several pulses to build up.
Integrated deep visual and semantic attractor neural networks predict fMRI pattern-information along the ventral object processing pathway
Authors: Devereux Barry J. , Clarke Alex , Tyler Lorraine K. 
Published: July 2018

AbstractRecognising an object involves rapid visual processing and activation of semantic knowledge about the object, but how visual processing activates and interacts with semantic representations remains unclear. Cognitive neuroscience research has shown that while visual processing involves posterior regions along the ventral stream, object meaning involves more anterior regions, especially perirhinal cortex. Here we investigate visuo-semantic processing by combining a deep neural network model of vision with an attractor network model of semantics, such that visual information maps onto object meanings represented as activation patterns across features. In the combined model, concept activation is driven by visual input and co-occurrence of semantic features, consistent with neurocognitive accounts. We tested the model’s ability to explain fMRI data where participants named objects. Visual layers explained activation patterns in early visual cortex, whereas pattern-information in perirhinal cortex was best explained by later stages of the attractor network, when detailed semantic representations are activated. Posterior ventral temporal cortex was best explained by intermediate stages corresponding to initial semantic processing, when visual information has the greatest influence on the emerging semantic representation. These results provide proof of principle of how a mechanistic model of combined visuo-semantic processing can account for pattern-information in the ventral stream.
Neonatal anesthesia exposure impacts brain microRNAs and their associated neurodevelopmental processes
Authors: Lin Daisy , Liu Jinyang , Hu Zihua , Cottrell James E. , Kass Ira S. 
Published: July 2018

AbstractMicroRNAs (miRNAs), when subjected to environmental stimuli, can exhibit differential expression. As critical regulators of gene expression, differential miRNA expression has been implicated in numerous disorders of the nervous system. In this study, we focused on the effect of a general anesthetic, as an environmental stimulus, on miRNA expression of the developing brain. General anesthetics have potential long-lasting neurotoxic effects on the developing brain, resulting in behavioral changes in adulthood. We first carried out an unbiased profiling approach to examine the effect of single-episode neonatal general anesthetic, sevoflurance (sevo), exposure on miRNA expression of the brain. Neonatal sevo has a significant effect on the expression of specific miRNAs of the whole brain and the hippocampus that is both immediate – directly after neonatal treatment, as well as long-lasting - during adulthood. Functionally, neonatal sevo-associated miRNA gene-targets share potential neurodevelopmental pathways related to axon guidance, DNA transcription, protein phosphorylation and nervous system development. Our understanding on the role of miRNAs provides a putative epigenetic/molecular bridge that links neonatal general anesthetic’s effect with its associated functional change.
Fate of mesoangioblasts in a vaginal birth injury model: influence of the route of administration
Authors: Mori da Cunha Marina Gabriela Monteiro Carvalho , Giacomazzi Giorgia , Callewaert Geertje , Hympanova Lucie , Russo Francesca , Vande Velde Greetje , Gijsbers Rik , Albersen Maarten , Sampaolesi Maurilio , Deprest Jan 
Published: July 2018

AbstractCurrently cell therapy is considered as an experimental strategy to assist the healing process following simulated vaginal birth injury in rats, boosting the functional and morphologic recovery of pelvic floor muscles and nerves. However, the optimal administration route and dose still need to be determined. Mesangioblasts theoretically have the advantage that they can differentiate in skeletal and smooth muscle. We investigated the fate of mesoangioblasts transduced with luciferase and green fluorescent protein reporter genes (rMABseGFP/fLUC) using bioluminescence, immunofluorescence and RT-PCR in rats undergoing simulated birth injury. rMABseGFP/fLUC were injected locally, intravenously and intra-arterially (common iliacs and aorta). Intra-arterial delivery resulted in the highest amount of rMABseGFP/fLUC in the pelvic organs region and in a more homogeneous distribution over all relevant pelvic organs. Sham controls showed that the presence of the injury is important for recruitment of intra-arterially injected rMABseGFP/fLUC. Injection through the aorta or bilaterally in the common iliac arteries resulted in comparable numbers of rMABseGFP/fLUC in the pelvic organs, yet aortic injection was faster and gave less complications.
The crustal geophysical signature of a world-class magmatic mineral system
Authors: Heinson Graham , Didana Yohannes , Soeffky Paul , Thiel Stephan , Wise Tom 
Published: July 2018

AbstractWorld-class magmatic mineral systems are characterised by fluid/melt originating in the deep crust and mantle. However, processes that entrain and focus fluids from a deep-source region to a kilometre-scale deposit through the crust are unclear. A magnetotelluric (MT) and reflection seismic program across the margin of the Gawler Craton, Australia yield a distinct signature for a 1590 Ma event associated with emplacement of iron-oxide copper gold uranium (IOCG-U) deposits. Two- and three-dimensional MT modelling images a 50 km wide lower-crustal region of resistivity <10 Ωm along an accreted Proterozoic belt. The least resistive (~1 Ωm) part terminates at the brittle-ductile transition at ~15 km, directly beneath a rifted sedimentary basin. Above the brittle-ductile transition, three narrow low-resistivity zones (~100 Ωm) branch to the surface. The least resistive zone is remarkably aligned with the world-class IOCG-U Olympic Dam deposit and the other two with significant known IOCG-U mineral occurrences. These zones are spatially correlated with narrow regions of low seismic reflectivity in the upper crust, and the deeper lower-crust conductor is almost seismically transparent. We argue this whole-of-crust imaging encapsulates deep mineral system and maps pathways of metalliferous fluids from crust and mantle sources to emplacement at discrete locations.
Codon usage clusters correlation: towards protein solubility prediction in heterologous expression systems in E. coli
Authors: Pellizza Leonardo , Smal Clara , Rodrigo Guido , Arán Martín 
Published: July 2018

AbstractProduction of soluble recombinant proteins is crucial to the development of industry and basic research. However, the aggregation due to the incorrect folding of the nascent polypeptides is still a mayor bottleneck. Understanding the factors governing protein solubility is important to grasp the underlying mechanisms and improve the design of recombinant proteins. Here we show a quantitative study of the expression and solubility of a set of proteins from Bizionia argentinensis. Through the analysis of different features known to modulate protein production, we defined two parameters based on the %MinMax algorithm to compare codon usage clusters between the host and the target genes. We demonstrate that the absolute difference between all %MinMax frequencies of the host and the target gene is significantly negatively correlated with protein expression levels. But most importantly, a strong positive correlation between solubility and the degree of conservation of codons usage clusters is observed for two independent datasets. Moreover, we evince that this correlation is higher in codon usage clusters involved in less compact protein secondary structure regions. Our results provide important tools for protein design and support the notion that codon usage may dictate translation rate and modulate co-translational folding.
The Functional Alterations in Top-Down Attention Streams of Parkinson’s disease Measured by EEG
Authors: Bin Yoo Hye , Concha Edgar Omar de la , De Ridder Dirk , Pickut Barbara A. , Vanneste Sven 
Published: July 2018

AbstractEarly and moderate Parkinson’s disease patients seem to have attention dysfunctions manifested differentially in separate attention streams: top-down and bottom-up. With a focus on the neurophysiological underpinnings of such differences, this study evaluated source-localized regional activity and functional connectivity of regions in the top-down and bottom-up streams as well as any discordance between the two streams. Resting state electroencephalography was used for 36 Parkinson’s disease patients and 36 healthy controls matched for age and gender. Parkinson’s disease patients showed disproportionally higher bilateral gamma activity in the bottom-up stream and higher left alpha2 connectivity in the top-down stream when compared to age-matched controls. An additional cross-frequency coupling analysis showed that Parkinson’s patients have higher alpha2-gamma coupling in the right posterior parietal cortex, which is part of the top-down stream. Higher coupling in this region was also associated with lower severity of motor symptoms in Parkinson’s disease. This study provides evidence that in Parkinson’s disease, the activity in gamma frequency band and connectivity in alpha2 frequency band is discordant between top-down and bottom-up attention streams.