bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Learning Brain
Authors: Ahr Emmanuel , Borst Grégoire , Houdé Olivier 
Published: February 2017

Abstract. Reading is an example of complex learning specific to human beings. In readers, an area of the brain is dedicated to the visual processing of letters and words, referred to as the visual word form area (VWFA). The existence of this brain area is paradoxical. Reading is too recent to be a phylogenic product of Darwinian evolution. It likely develops with intense school training via a neuroplastic ontogenic process of neuronal recycling: neurons in the lateral occipitotemporal lobe originally tuned to the visual recognition of stimuli, such as faces, objects, and animals, will be recycled for the visual recognition of letters and words. Thus, the VWFA inherits the intrinsic properties of these neurons, notably, mirror generalization, a process (or heuristic) applied to all visual stimuli that enables the recognition of a stimulus irrespective of its left-right orientation. On its own, this inherited property is not adapted to reading because it makes children confuse mirror letters, such as b and d in the Latin alphabet. In this article, we present evidence that inhibitory control is critical to avoid mirror errors inherited from the neuronal recycling process by blocking the mirror generalization heuristic in the context of reading. We subsequently argue that the “neuronal recycling + inhibitory control” law constitutes a general law of the learning brain by demonstrating that it may also account for the development of numeracy.
Coordinate activities of BRD4 and CDK9 in the transcriptional elongation complex are required for TGFβ-induced Nox4 expression and myofibroblast transdifferentiation
Authors: Ijaz Talha , Jamaluddin Mohammad , Zhao Yingxin , Zhang Yueqing , Jay Jayson , Finnerty Celeste C , Herndon David N , Tilton Ronald G , Brasier Allan R 
Published: February 2017

AbstractTransdifferentiation of quiescent dermal fibroblasts to secretory myofibroblasts has a central role in wound healing and pathological scar formation. This myofibroblast transdifferentiation process involves TGFβ-induced de novo synthesis of alpha smooth muscle cell actin (αSMA)+ fibers that enhance contractility as well as increased expression of extracellular matrix (ECM) proteins, including collagen and fibronectin. These processes are mediated upstream by the reactive oxygen species (ROS)-producing enzyme Nox4, whose induction by TGFβ is incompletely understood. In this study, we demonstrate that Nox4 is involved in αSMA+ fiber formation and collagen production in primary human dermal fibroblasts (hDFs) using a small-molecule inhibitor and siRNA-mediated silencing. Furthermore, TGFβ-induced signaling via Smad3 is required for myofibroblast transformation and Nox4 upregulation. Immunoprecipitation-selected reaction monitoring (IP-SRM) assays of the activated Smad3 complex suggest that it couples with the epigenetic reader and transcription co-activator bromodomain and extraterminal (BET) domain containing protein 4 (BRD4) to promote Nox4 transcription. In addition, cyclin-dependent kinase 9 (CDK9), a component of positive transcription elongation factor, binds to BRD4 after TGFβ stimulation and is also required for RNA polymerase II phosphorylation and Nox4 transcription regulation. Surprisingly, BRD4 depletion decreases myofibroblast differentiation but does not affect collagen or fibronectin expression in primary skin fibroblasts, whereas knockdown of CDK9 decreases all myofibroblast genes. We observe enhanced numbers and persistence of myofibroblast formation and TGFβ signaling in hypertrophic scars. BRD4 inhibition reverses hypertrophic skin fibroblast transdifferentiation to myofibroblasts. Our data indicate that BRD4 and CDK9 have independent, coordinated roles in promoting the myofibroblast transition and suggest that inhibition of the Smad3-BRD4 pathway may be a useful strategy to limit hypertrophic scar formation after burn injury.
Luteolin selectively kills STAT3 highly activated gastric cancer cells through enhancing the binding of STAT3 to SHP-1
Authors: Song Shiyu , Su Zhonglan , Xu Hui , Niu Mengyuan , Chen Xiufang , Min Haiyan , Zhang Bin , Sun Guibo , Xie Sijing , Wang Hongwei , Gao Qian 
Published: February 2017

AbstractThe antitumor effect of luteolin, a plant flavonoid, in gastric cancer (GC) cells has not been fully understood. Here we show that luteolin selectively kills STAT3 overactivated GC cells that are often drug resistant. The treatment of luteolin in these GC cells significantly inhibited STAT3 phosphorylation and reduced the expression of STAT3 targeting gene Mcl-1, Survivin and Bcl-xl. Silencing of SHP-1, a protein tyrosine phosphatase, abolished the inhibitory effect of luteolin on STAT3 and cell apoptosis, suggesting that SHP-1 is crucial in luteolin-mediated cellular function. Moreover, this luteolin effect of STAT3 dephosphorylation by SHP-1 involved in HSP-90, which protected STAT3 phosphorylation by forming HSP-90/STAT3 complex. Thus, luteolin inhibited STAT3 activation through disrupting the binding of HSP-90 to STAT3, which promoted its interaction to SHP-1, resulted in the dephosphorylation of STAT3. The GC cell xenograft mouse model confirmed the effectiveness of luteolin induced inhibition of tumor growth in vivo.
Thioridazine enhances sensitivity to carboplatin in human head and neck cancer cells through downregulation of c-FLIP and Mcl-1 expression
Authors: Seo Seung Un , Cho Hyuk Ki , Min Kyoung-jin , Woo Seon Min , Kim Shin , Park Jong-Wook , Kim Sang Hyun , Choi Yung Hyun , Keum Young Sam , Hyun Jin Won , Park Hyun Ho , Lee Sang-Han , Kim Dong Eun , Kwon Taeg Kyu 
Published: February 2017

AbstractCarboplatin is a less toxic analog of cisplatin, but carboplatin also has side effects, including bone marrow suppression. Therefore, to improve the capacity of the anticancer activity of carboplatin, we investigated whether combined treatment with carboplatin and thioridazine, which has antipsychotic and anticancer activities, has a synergistic effect on apoptosis. Combined treatment with carboplatin and thioridazine markedly induced caspase-mediated apoptosis in head and neck squamous cell carcinoma (AMC-HN4) cells. Combined treatment with carboplatin and thioridazine induced downregulation of Mcl-1 and c-FLIP expression. Ectopic expression of Mcl-1 and c-FLIP inhibited carboplatin plus thioridazine-induced apoptosis. We found that augmentation of proteasome activity had a critical role in downregulation of Mcl-1 and c-FLIP expression at the post-translational level in carboplatin plus thioridazine-treated cells. Furthermore, carboplatin plus thioridazine induced upregulation of the expression of proteasome subunit alpha 5 (PSMA5) through mitochondrial reactive oxygen species (ROS)-dependent nuclear factor E2-related factor 2 (Nrf2) activation. In addition, combined treatment with carboplatin and thioridazine markedly induced apoptosis in human breast carcinoma (MDA-MB231) and glioma (U87MG) cells, but not in human normal mesangial cells and normal human umbilical vein cells (EA.hy926). Collectively, our study demonstrates that combined treatment with carboplatin and thioridazine induces apoptosis through proteasomal degradation of Mcl-1 and c-FLIP by upregulation of Nrf2-dependent PSMA5 expression.
Chip-based quantum key distribution
Authors: Sibson P. , Erven C. , Godfrey M. , Miki S. , Yamashita T. , Fujiwara M. , Sasaki M. , Terai H. , Tanner M. G. , Natarajan C. M. , Hadfield R. H. , O’Brien J. L. , Thompson M. G. 
Published: February 2017

AbstractImprovement in secure transmission of information is an urgent need for governments, corporations and individuals. Quantum key distribution (QKD) promises security based on the laws of physics and has rapidly grown from proof-of-concept to robust demonstrations and deployment of commercial systems. Despite these advances, QKD has not been widely adopted, and large-scale deployment will likely require chip-based devices for improved performance, miniaturization and enhanced functionality. Here we report low error rate, GHz clocked QKD operation of an indium phosphide transmitter chip and a silicon oxynitride receiver chip—monolithically integrated devices using components and manufacturing processes from the telecommunications industry. We use the reconfigurability of these devices to demonstrate three prominent QKD protocols—BB84, Coherent One Way and Differential Phase Shift—with performance comparable to state-of-the-art. These devices, when combined with integrated single photon detectors, pave the way for successfully integrating QKD into future telecommunications networks.
Natural amines inhibit activation of human plasmacytoid dendritic cells through CXCR4 engagement
Authors: Smith Nikaïa , Pietrancosta Nicolas , Davidson Sophia , Dutrieux Jacques , Chauveau Lise , Cutolo Pasquale , Dy Michel , Scott-Algara Daniel , Manoury Bénédicte , Zirafi Onofrio , McCort-Tranchepain Isabelle , Durroux Thierry , Bachelerie Françoise , Schwartz Olivier , Münch Jan , Wack Andreas , Nisole Sébastien , Herbeuval Jean-Philippe 
Published: February 2017

AbstractPlasmacytoid dendritic cells (pDC) are specialized in secretion of type I interferon in response to pathogens. Here we show that natural monoamines and synthetic amines inhibit pDC activation by RNA viruses. Furthermore, a synthetic analogue of histamine reduces type I interferon production in a mouse model of influenza infection. We identify CXC chemokine receptor 4 (CXCR4) as a receptor used by amines to inhibit pDC. Our study establishes a functional link between natural amines and the innate immune system and identifies CXCR4 as a potential ‘on-off’ switch of pDC activity with therapeutic potential.
Molecular composition of organic matter controls methylmercury formation in boreal lakes
Authors: Bravo Andrea G. , Bouchet Sylvain , Tolu Julie , Björn Erik , Mateos-Rivera Alejandro , Bertilsson Stefan 
Published: February 2017

AbstractA detailed understanding of the formation of the potent neurotoxic methylmercury is needed to explain the large observed variability in methylmercury levels in aquatic systems. While it is known that organic matter interacts strongly with mercury, the role of organic matter composition in the formation of methylmercury in aquatic systems remains poorly understood. Here we show that phytoplankton-derived organic compounds enhance mercury methylation rates in boreal lake sediments through an overall increase of bacterial activity. Accordingly, in situ mercury methylation defines methylmercury levels in lake sediments strongly influenced by planktonic blooms. In contrast, sediments dominated by terrigenous organic matter inputs have far lower methylation rates but higher concentrations of methylmercury, suggesting that methylmercury was formed in the catchment and imported into lakes. Our findings demonstrate that the origin and molecular composition of organic matter are critical parameters to understand and predict methylmercury formation and accumulation in boreal lake sediments.
Dpath software reveals hierarchical haemato-endothelial lineages of Etv2 progenitors based on single-cell transcriptome analysis
Authors: Gong Wuming , Rasmussen Tara L. , Singh Bhairab N. , Koyano-Nakagawa Naoko , Pan Wei , Garry Daniel J. 
Published: February 2017

AbstractDevelopmental, stem cell and cancer biologists are interested in the molecular definition of cellular differentiation. Although single-cell RNA sequencing represents a transformational advance for global gene analyses, novel obstacles have emerged, including the computational management of dropout events, the reconstruction of biological pathways and the isolation of target cell populations. We develop an algorithm named dpath that applies the concept of metagene entropy and allows the ranking of cells based on their differentiation potential. We also develop self-organizing map (SOM) and random walk with restart (RWR) algorithms to separate the progenitors from the differentiated cells and reconstruct the lineage hierarchies in an unbiased manner. We test these algorithms using single cells from Etv2-EYFP transgenic mouse embryos and reveal specific molecular pathways that direct differentiation programmes involving the haemato-endothelial lineages. This software program quantitatively assesses the progenitor and committed states in single-cell RNA-seq data sets in a non-biased manner.
Small genomic insertions form enhancers that misregulate oncogenes
Authors: Abraham Brian J. , Hnisz Denes , Weintraub Abraham S. , Kwiatkowski Nicholas , Li Charles H. , Li Zhaodong , Weichert-Leahey Nina , Rahman Sunniyat , Liu Yu , Etchin Julia , Li Benshang , Shen Shuhong , Lee Tong Ihn , Zhang Jinghui , Look A. Thomas , Mansour Marc R. , Young Richard A. 
Published: February 2017

AbstractThe non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challenges with interpreting short-read DNA sequences. Here, using a combination of Chip-seq to enrich enhancer DNA and a computational approach with multiple DNA alignment procedures, we identify enhancer-associated small insertion variants. Among the 102 tumour cell genomes we analyse, small insertions are frequently observed in enhancer DNA sequences near known oncogenes. Further study of one insertion, somatically acquired in primary leukaemia tumour genomes, reveals that it nucleates formation of an active enhancer that drives expression of the LMO2 oncogene. The approach described here to identify enhancer-associated small insertion variants provides a foundation for further study of these abnormalities across human cancers.
Wide-range ideal 2D Rashba electron gas with large spin splitting in Bi2Se3/MoTe2 heterostructure
Authors: Wang Te-Hsien , Jeng Horng-Tay 
Published: February 2017

AbstractAn application-expected ideal two-dimensional Rashba electron gas, i.e., nearly all the conduction electrons occupy the Rashba bands, is crucial for semiconductor spintronic applications. We demonstrate that such an ideal two-dimensional Rashba electron gas with a large Rashba splitting can be realized in a topological insulator Bi2Se3 ultrathin film grown on a transition metal dichalcogenides MoTe2 substrate through first-principle calculations. Our results show the Rashba bands exclusively over a very large energy interval of about 0.6 eV around the Fermi level within the MoTe2 semiconducting gap. Such a wide-range ideal two-dimensional Rashba electron gas with a large spin splitting, which is desirable for real devices utilizing the Rashba effect, has never been found before. Due to the strong spin–orbit coupling, the strength of the Rashba splitting is comparable with that of the heavy-metal surfaces such as Au and Bi surfaces, giving rise to a spin precession length as small as ~10 nm. The maximum in-plane spin polarization of the inner (outer) Rashba band near the Γ point is about 70% (60%). The room-temperature coherence length is at least several times longer than the spin precession length, providing good coherency through the spin processing devices. The wide energy window for ideal Rashba bands, small spin precession length, as well as long spin coherence length in this two-dimensional topological insulator/transition metal dichalcogenides heterostructure pave the way for realizing an ultrathin nano-scale spintronic device such as the Datta–Das spin transistor at room-temperature.
Escherichia coli-derived virus-like particles in vaccine development
Authors: Huang Xiaofen , Wang Xin , Zhang Jun , Xia Ningshao , Zhao Qinjian 
Published: February 2017

AbstractRecombinant virus-like particle-based vaccines are composed of viral structural proteins and mimic authentic native viruses but are devoid of viral genetic materials. They are the active components in highly safe and effective vaccines for the prevention of infectious diseases. Several expression systems have been used for virus-like particle production, ranging fromEscherichia colito mammalian cell lines. The prokaryotic expression system, especiallyEscherichia coli, is the preferred expression host for producing vaccines for global use. Hecolin, the first licensed virus-like particle vaccine derived fromEscherichia coli, has been demonstrated to possess good safety and high efficacy. In this review, we focus onEscherichia coli-derived virus-like particle based vaccines and vaccine candidates that are used for prevention (immunization against microbial pathogens) or disease treatment (directed against cancer or non-infectious diseases). The native-like spatial or higher-order structure is essential for the function of virus-like particles. Thus, the tool box for analyzing the key physicochemical, biochemical and functional attributes of purified virus-like particles will also be discussed. In summary, theEscherichia coliexpression system has great potentials for producing a range of proteins with self-assembling properties to be used as vaccine antigens given the proper epitopes were preserved when compared to those in the native pathogens or disease-related target molecules.
Genome-wide association study for performance traits in chickens using genotype by sequencing approach
Authors: Pértille Fábio , Moreira Gabriel Costa Monteiro , Zanella Ricardo , Nunes José de Ribamar da Silva , Boschiero Clarissa , Rovadoscki Gregori Alberto , Mourão Gerson Barreto , Ledur Mônica Corrêa , Coutinho Luiz Lehmann 
Published: February 2017

AbstractPerformance traits are economically important and are targets for selection in breeding programs, especially in the poultry industry. To identify regions on the chicken genome associated with performance traits, different genomic approaches have been applied in the last years. The aim of this study was the application of CornellGBS approach (134,528 SNPs generated from aPstIrestriction enzyme) on Genome-Wide Association Studies (GWAS) in an outbred F2chicken population. We have validated 91.7% of these 134,528 SNPs after imputation of missed genotypes. Out of those, 20 SNPs were associated with feed conversion, one was associated with body weight at 35 days of age (P < 7.86E-07) and 93 were suggestively associated with a variety of performance traits (P < 1.57E-05). The majority of these SNPs (86.2%) overlapped with previously mapped QTL for the same performance traits and some of the SNPs also showed novel potential QTL regions. The results obtained in this study suggests future searches for candidate genes and QTL refinements as well as potential use of the SNPs described here in breeding programs.
Involvement of β-defensin 130 (DEFB130) in the macrophage microbicidal mechanisms for killing Plasmodium falciparum
Authors: Terkawi Mohamad Alaa , Takano Ryo , Furukawa Atsushi , Murakoshi Fumi , Kato Kentaro 
Published: February 2017

AbstractUnderstanding the molecular defense mechanism of macrophages and identifying their effector molecules against malarial parasites may provide important clues for the discovery of new therapies. To analyze the immunological responses of malarial parasite-induced macrophages, we used DNA microarray technology to examine the gene profile of differentiated macrophages phagocytizing Plasmodium falciparum-parasitized erythrocytes (iRBC). The transcriptional gene profile of macrophages in response to iRBCs represented 168 down-regulated genes, which were mainly involved in the cellular immune response, and 216 upregulated genes, which were involved in cellular proteolysis, growth, and adhesion. Importantly, the specific upregulation of β-defensin 130 (DEFB130) in these macrophages suggested a possible role for DEFB130 in malarial parasite elimination. Differentiated macrophages phagocytizing iRBCs exhibited an increase in intracellular DEFB130 levels and DEFB130 appeared to accumulate at the site of iRBC engulfment. Transfection of esiRNA-mediated knockdown of DEFB130 into macrophages resulted in a remarkable reduction in their antiplasmodial activity in vitro. Furthermore, DEFB130 synthetic peptide exhibited a modest toxic effect on P. falciparum in vitro and P. yoelii in vivo, unlike scrambled DEFB130 peptide, which showed no antiplasmodial activity. Together, these results suggest that DEFB130 might be one of the macrophage effector molecules for eliminating malarial parasites. Our data broaden our knowledge of the immunological response of macrophages to iRBCs and shed light on a new target for therapeutic intervention.
Precise measurement of ultra-narrow laser linewidths using the strong coherent envelope
Authors: Huang Shihong , Zhu Tao , Liu Min , Huang Wei 
Published: February 2017

AbstractLaser linewidth narrowing down to kHz or even Hz is an important topic in areas like clock synchronization technology, laser radars, quantum optics, and high-precision detection. Conventional decoherence measurement methods like delayed self-heterodyne/homodyne interferometry cannot measure such narrow linewidths accurately. This is because a broadening of the Gaussian spectrum, which hides the laser’s intrinsic Lorentzian linewidth, cannot be avoided. Here, we introduce a new method using the strong coherent envelope to characterize the laser’s intrinsic linewidth through self-coherent detection. This method can eliminate the effect of the broadened Gaussian spectrum induced by the 1/f frequency noise. We analyze, in detail, the relationship between intrinsic laser linewidth, contrast difference with the second peak and the second trough (CDSPST) of the strong coherent envelope, and the length of the delaying fiber. The correct length for the delaying fiber can be chosen by combining the estimated laser linewidth (Δfest) with a specific CDSPST (ΔS) to obtain the accurate laser linewidth (Δf). Our results indicate that this method can be used as an accurate detection tool for measurements of narrow or super-narrow linewidths.
Gene variation in IL-7 receptor (IL-7R)α affects IL-7R response in CD4+ T cells in HIV-infected individuals
Authors: Hartling Hans Jakob , Ryder Lars P. , Ullum Henrik , Ødum Niels , Nielsen Susanne Dam 
Published: February 2017

AbstractOptimal CD4+ T cell recovery after initiating combination antiretroviral treatment (cART) in HIV infection reduces risk of morbidity and mortality. T-allele homozygosity (‘TT’) in the single nucleotide polymorphism, rs6897932(C/T), in the IL-7 receptor α (IL-7RA) is associated with faster CD4+ T cell recovery after cART initiation compared to C-allele homozygosity in rs6897932 (‘CC’). However, underlying mechanisms are unknown. We aimed to examine potential mechanisms explaining the association between rs6897932 and CD4+ T cell recovery. Ten ‘TT’ and 10 ‘CC’ HIV-infected individuals matched on gender, age, and nadir and current CD4+ T cell counts were included in a cross-sectional study. ‘TT’ individuals had higher proportion of CD4+ T cells expressing pSTAT5 compared to ‘CC’ individuals after stimulating with IL-7, especially when co-stimulated with soluble IL7-RA (sIL-7RA). Furthermore, ‘TT’ individuals had a higher proportion of proliferating CD4+ T cells after 7 days of culture with IL-7 + sIL-7RA compared to ‘CC’ individuals. No differences between ‘TT’ and ‘CC’ in binding of biotinylated IL-7 were found. In conclusion, increased signal transduction and proliferation in response to IL-7 was found in ‘TT’ compared to ‘CC’ HIV-infected individuals providing a mechanistic explanation of the effect of rs6897932 T-allele on CD4+ T cell recovery in HIV infection.