bluuebunny/crossref_metadata_2025_split huggingface dataset:
Degranulation of mast cells induced by gastric cancer-derived adrenomedullin prompts gastric cancer progression
Authors: Lv Yi-pin , Peng Liu-sheng , Wang Qi-hong , Chen Na , Teng Yong-sheng , Wang Ting-ting , Mao Fang-yuan , Zhang Jin-yu , Cheng Ping , Liu Yu-gang , Kong Hui , Wu Xiao-long , Hao Chuan-jie , Chen Weisan , Zhu Jiang , Han Bin , Ma Qiang , Li Ke , Zou Quanming , Zhuang Yuan 
Published: October 2018

AbstractMast cells are prominent components of solid tumors and exhibit distinct phenotypes in different tumor microenvironments. However, their precise mechanism of communication in gastric cancer remains largely unclear. Here, we found that patients with GC showed a significantly higher mast cell infiltration in tumors. Mast cell levels increased with tumor progression and independently predicted reduced overall survival. Tumor-derived adrenomedullin (ADM) induced mast cell degranulation via PI3K-AKT signaling pathway, which effectively promoted the proliferation and inhibited the apoptosis of GC cells in vitro and contributed to the growth and progression of GC tumors in vivo, and the effect could be reversed by blocking interleukin (IL)-17A production from these mast cells. Our results illuminate a novel protumorigenic role and associated mechanism of mast cells in GC, and also provide functional evidence for these mast cells to prevent, and to treat this immunopathogenesis feature of GC.
DNA-methylation-mediated silencing of miR-486-5p promotes colorectal cancer proliferation and migration through activation of PLAGL2/IGF2/β-catenin signal pathways
Authors: Liu Xiangxiang , Chen Xiaoxiang , Zeng Kaixuan , Xu Mu , He Bangshun , Pan Yuqin , Sun Huiling , Pan Bei , Xu Xueni , Xu Tao , Hu Xiuxiu , Wang Shukui 
Published: October 2018

AbstractAs one of the most common cancers worldwide, colorectal cancer (CRC) causes a large number of mortality annually. Aberrant expression of microRNAs (miRNAs) is significantly associated with the initiation and development of CRC. Further investigations regarding the regulatory mechanism of miRNAs is warranted. In this study, we discovered that miR-486-5p was remarkably downregulated in CRC, which partially results from higher DNA methylation in the promoter region detected by using methylation-specific PCR, bisulfite sequencing PCR, and DNA demethylation treatment. Besides, decreased miR-486-5p was obviously associated with advanced TNM stage, larger tumor size, lymphatic metastasis, and poor prognosis in CRC. Upregulated miR-486-5p inhibited the proliferation and migration of CRC through targeting PLAGL2 expression and subsequent repressing IGF/β-catenin signal pathways both in vitro and in vivo. Notably, plasma miR-486-5p expression was significantly upregulated in CRC patients and we identified plasma miR-486-5p as a novel diagnostic biomarker of CRC using receiver operating characteristic (ROC) curve analysis. Moreover, exploration in GEO dataset revealed that circulating miR-486-5p is tumor derived through being packaged into secretory exosomes. Taken together, our data demonstrated that miR-486-5p promotes colorectal cancer proliferation and migration through activation of PLAGL2/IGF2/β-catenin signal pathway, which is a promising therapeutic target of CRC treatment.
More complete polarization of renal tubular epithelial cells by artificial urine
Authors: Vinaiphat Arada , Charngkaew Komgrid , Thongboonkerd Visith 
Published: October 2018

AbstractCell polarization using Transwell is a common method employed to study renal tubular epithelial cells. However, this conventional protocol does not precisely recapitulate renal tubular epithelial cell phenotypes. In this study, we simulated renal physiological microenvironment by replacing serum-containing culture medium in upper chamber of the Transwell with physiologic artificial urine (AU) (to mimic renal tubular fluid), whereas the lower chamber still contained serum-containing medium (to mimic plasma-enriched renal interstitium). Comparing to the conventional protocol (control), the AU-assisted protocol offered more complete polarization of MDCK renal tubular cells as indicated by higher transepithelial electrical resistance (TER) and greater levels of tight junction (TJ) proteins (ZO-1 and occludin). Transmission electron microscopy (TEM) showed greater densities of TJ and desmosome, narrower intercellular spaces, greater cell height, and longer microvilli in the AU-treated cells. Secretome analysis revealed that the AU-treated cells secreted greater proportion of the proteins matched to normal human urinary proteome via both classical and non-classical secretory pathways. Finally, modifying/omitting each component of AU (one at a time) followed by validation revealed that urea was responsible for such property of AU to improve cell polarization. These data indicate that replacing AU on the upper chamber of Transwell can improve or optimize renal cell polarization for more precise investigations of renal physiology and cell biology in vitro.
Haploinsufficiency of autism spectrum disorder candidate gene NUAK1 impairs cortical development and behavior in mice
Authors: Courchet Virginie , Roberts Amanda J. , Meyer-Dilhet Géraldine , Del Carmine Peggy , Lewis Tommy L. , Polleux Franck , Courchet Julien 
Published: October 2018

AbstractRecently, numerous rare de novo mutations have been identified in patients diagnosed with autism spectrum disorders (ASD). However, despite the predicted loss-of-function nature of some of these de novo mutations, the affected individuals are heterozygous carriers, which would suggest that most of these candidate genes are haploinsufficient and/or lead to expression of dominant-negative forms of the protein. Here, we tested this hypothesis with the candidate ASD gene Nuak1 that we previously identified for its role in the development of cortical connectivity. We report that Nuak1 is haploinsufficient in mice with regard to its function in cortical development. Furthermore Nuak1+/− mice show a combination of abnormal behavioral traits ranging from defective spatial memory consolidation, defects in social novelty (but not social preference) and abnormal sensorimotor gating. Overall, our results demonstrate that Nuak1 haploinsufficiency leads to defects in the development of cortical connectivity and a complex array of behavorial deficits.
Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation
Authors: Liang Huiyi , Peng Bo , Dong Cong , Liu Lixin , Mao Jiaji , Wei Song , Wang Xinlu , Xu Hanshi , Shen Jun , Mao Hai-Quan , Gao Xiaohu , Leong Kam W. , Chen Yongming 
Published: October 2018

AbstractCell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here we show that ~40 nm cationic nanoparticles (cNP) can scavenge cfDNA derived from RA patients and inhibit the activation of primary synovial fluid monocytes and fibroblast-like synoviocytes. Using clinical scoring, micro-CT images, MRI, and histology, we show that intravenous injection of cNP into a CpG-induced mouse model or collagen-induced arthritis rat model can relieve RA symptoms including ankle and tissue swelling, and bone and cartilage damage. This culminates in the manifestation of partial mobility recovery of the treated rats in a rotational cage test. Mechanistic studies on intracellular trafficking and biodistribution of cNP, as well as measurement of cytokine expression in the joints and cfDNA levels in systemic circulation and inflamed joints also correlate with therapeutic outcomes. This work suggests a new direction of nanomedicine in treating inflammatory diseases.
Cancer exosomes induce tumor innervation
Authors: Madeo Marianna , Colbert Paul L. , Vermeer Daniel W. , Lucido Christopher T. , Cain Jacob T. , Vichaya Elisabeth G. , Grossberg Aaron J. , Muirhead DesiRae , Rickel Alex P. , Hong Zhongkui , Zhao Jing , Weimer Jill M. , Spanos William C. , Lee John H. , Dantzer Robert , Vermeer Paola D. 
Published: October 2018

AbstractPatients with densely innervated tumors suffer with increased metastasis and decreased survival as compared to those with less innervated tumors. We hypothesize that in some tumors, nerves are acquired by a tumor-induced process, called axonogenesis. Here, we use PC12 cells as an in vitro neuronal model, human tumor samples and murine in vivo models to test this hypothesis. When appropriately stimulated, PC12 cells extend processes, called neurites. We show that patient tumors release vesicles, called exosomes, which induce PC12 neurite outgrowth. Using a cancer mouse model, we show that tumors compromised in exosome release are less innervated than controls. Moreover, in vivo pharmacological blockade of exosome release similarly attenuates tumor innervation. We characterize these nerves as sensory in nature and demonstrate that axonogenesis is potentiated by the exosome-packaged axonal guidance molecule, EphrinB1. These findings indicate that tumor released exosomes induce tumor innervation and exosomes containing EphrinB1 potentiate this activity.
Human breast tumor-infiltrating CD8+ T cells retain polyfunctionality despite PD-1 expression
Authors: Egelston Colt A. , Avalos Christian , Tu Travis Y. , Simons Diana L. , Jimenez Grecia , Jung Jae Y. , Melstrom Laleh , Margolin Kim , Yim John H. , Kruper Laura , Mortimer Joanne , Lee Peter P. 
Published: October 2018

AbstractFunctional CD8+T cells in human tumors play a clear role in clinical prognosis and response to immunotherapeutic interventions. PD-1 expression in T cells involved in chronic infections and tumors such as melanoma often correlates with a state of T-cell exhaustion. Here we interrogate CD8+tumor-infiltrating lymphocytes (TILs) from human breast and melanoma tumors to explore their functional state. Despite expression of exhaustion hallmarks, such as PD-1 expression, human breast tumor CD8+TILs retain robust capacity for production of effector cytokines and degranulation capacity. In contrast, melanoma CD8+TILs display dramatic reduction of cytokine production and degranulation capacity. We show that CD8+TILs from human breast tumors can potently kill cancer cells via bi-specific antibodies. Our data demonstrate that CD8+TILs in human breast tumors retain polyfunctionality, despite PD-1 expression, and suggest that they may be harnessed for effective immunotherapies.
Shaping the topology of folding pathways in mechanical systems
Authors: Stern Menachem , Jayaram Viraaj , Murugan Arvind 
Published: October 2018

AbstractDisordered mechanical systems, when strongly deformed, have complex configuration spaces with multiple stable states and pathways connecting them. The topology of such pathways determines which states are smoothly accessible from any part of configuration space. Controlling this topology would allow us to limit access to undesired states and select desired behaviors in metamaterials. Here, we show that the topology of such pathways, as captured by bifurcation diagrams, can be tuned using imperfections such as stiff hinges in elastic networks and creased thin sheets. We derive Linear Programming-like equations for designing desirable pathway topologies. These ideas are applied to eliminate the exponentially many ways of misfolding self-folding sheets by making some creases stiffer than others. Our approach allows robust folding by entire classes of external folding forces. Finally, we find that the bifurcation diagram makes pathways accessible only at specific folding speeds, enabling speed-dependent selection of different folded states.
Action sharpens sensory representations of expected outcomes
Authors: Yon Daniel , Gilbert Sam J. , de Lange Floris P. , Press Clare 
Published: October 2018

AbstractWhen we produce actions we predict their likely consequences. Dominant models of action control suggest that these predictions are used to ‘cancel’ perceptual processing of expected outcomes. However, normative Bayesian models of sensory cognition developed outside of action propose that rather than being cancelled, expected sensory signals are represented with greater fidelity (sharpened). Here, we distinguished between these models in an fMRI experiment where participants executed hand actions (index vs little finger movement) while observing movements of an avatar hand. Consistent with the sharpening account, visual representations of hand movements (index vs little finger) could be read out more accurately when they were congruent with action and these decoding enhancements were accompanied by suppressed activity in voxels tuned away from, not towards, the expected stimulus. Therefore, inconsistent with dominant action control models, these data show that sensorimotor prediction sharpens expected sensory representations, facilitating veridical perception of action outcomes.
A selenium-catalysed para-amination of phenols
Authors: Yan Dingyuan , Wang Guoqiang , Xiong Feng , Sun Wei-Yin , Shi Zhuangzhi , Lu Yi , Li Shuhua , Zhao Jing 
Published: October 2018

AbstractAntioxidant enzyme glutathione peroxidase (GPx) decomposes hydroperoxides by utilizing the different redox chemistry of the selenium and sulfur. Here, we report a Se-catalysed para-amination of phenols while, in contrast, the reactions with sulfur donors are stoichiometric. A catalytic amount of phenylselenyl bromide smoothly converts N-aryloxyacetamides to N-acetyl p-aminophenols. When the para position was substituted (for example, with tyrosine), the dearomatization 4,4-disubstituted cyclodienone products were obtained. A combination of experimental and computational studies was conducted and suggested the weaker Se−N bond plays a key role in the completion of the catalytic cycle. Our method extends the selenium-catalysed processes to the functionalisation of aromatic compounds. Finally, we demonstrated the mild nature of the para-amination reaction by generating an AIEgen 2-(2′-hydroxyphenyl)benzothiazole (HBT) product in a fluorogenic fashion in a PBS buffer.
Narrow bandgap oxide nanoparticles coupled with graphene for high performance mid-infrared photodetection
Authors: Yu Xuechao , Li Yangyang , Hu Xiaonan , Zhang Daliang , Tao Ye , Liu Zhixiong , He Yongmin , Haque Md. Azimul , Liu Zheng , Wu Tom , Wang Qi Jie 
Published: October 2018

AbstractThe pursuit of optoelectronic devices operating in the mid-infrared regime is driven by both fundamental interests and envisioned applications ranging from imaging, sensing to communications. Despite continued achievements in traditional semiconductors, notorious obstacles such as the complicated growth processes and cryogenic operation preclude the usage of infrared detectors. As an alternative path towards high-performance photodetectors, hybrid semiconductor/graphene structures have been intensively explored. However, the operation bandwidth of such photodetectors has been limited to visible and near-infrared regimes. Here we demonstrate a mid-infrared hybrid photodetector enabled by coupling graphene with a narrow bandgap semiconductor, Ti2O3 (Eg = 0.09 eV), which achieves a high responsivity of 300 A W−1 in a broadband wavelength range up to 10 µm. The obtained responsivity is about two orders of magnitude higher than that of the commercial mid-infrared photodetectors. Our work opens a route towards achieving high-performance optoelectronics operating in the mid-infrared regime.
Dopamine-dependent prefrontal reactivations explain long-term benefit of fear extinction
Authors: Gerlicher A. M. V. , Tüscher O. , Kalisch R. 
Published: October 2018

AbstractFear extinction does not prevent post-traumatic stress or have long-term therapeutic benefits in fear-related disorders unless extinction memories are easily retrieved at later encounters with the once-threatening stimulus. Previous research in rodents has pointed towards a role for spontaneous prefrontal activity occurring after extinction learning in stabilizing and consolidating extinction memories. In other memory domains spontaneous post-learning activity has been linked to dopamine. Here, we show that a neural activation pattern — evoked in the ventromedial prefrontal cortex (vmPFC) by the unexpected omission of the feared outcome during extinction learning — spontaneously reappears during postextinction rest. The number of spontaneous vmPFC pattern reactivations predicts extinction memory retrieval and vmPFC activation at test 24 h later. Critically, pharmacologically enhancing dopaminergic activity during extinction consolidation amplifies spontaneous vmPFC reactivations and correspondingly improves extinction memory retrieval at test. Hence, a spontaneous dopamine-dependent memory consolidation-based mechanism may underlie the long-term behavioral effects of fear extinction.
Tailoring near-field thermal radiation between metallo-dielectric multilayers using coupled surface plasmon polaritons
Authors: Lim Mikyung , Song Jaeman , Lee Seung S. , Lee Bong Jae 
Published: October 2018

AbstractSeveral experiments have shown a huge enhancement in thermal radiation over the blackbody limit when two objects are separated by nanoscale gaps. Although those measurements only demonstrated enhanced radiation between homogeneous materials, theoretical studies now focus on controlling the near-field radiation by tuning surface polaritons supported in nanomaterials. Here, we experimentally demonstrate near-field thermal radiation between metallo-dielectric multilayers at nanoscale gaps. Significant enhancement in heat transfer is achieved due to the coupling of surface plasmon polaritons (SPPs) supported at multiple metal-dielectric interfaces. This enables the metallo-dielectric multilayers at a 160-nm vacuum gap to have the same heat transfer rate as that between semi-infinite metal surfaces separated by only 75 nm. We also demonstrate that near-field thermal radiation can be readily tuned by modifying the resonance condition of coupled SPPs. This study will provide a new direction for exploiting surface-polariton-mediated near-field thermal radiation between planar structures.
MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy
Authors: Liu Feng , Chen Jianxia , Wang Peng , Li Haohao , Zhou Yilong , Liu Haipeng , Liu Zhonghua , Zheng Ruijuan , Wang Lin , Yang Hua , Cui Zhenling , Wang Fei , Huang Xiaochen , Wang Jie , Sha Wei , Xiao Heping , Ge Baoxue 
Published: October 2018

AbstractTuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb, the role of calcium (Ca2+) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb-infected mice and macrophages. The target of miR-27a is the ER-located Ca2+ transporter CACNA2D3. Targeting of this transporter leads to the downregulation of Ca2+ signaling, thus inhibiting autophagosome formation and promoting the intracellular survival of Mtb. Mice lacking of miR-27a and mice treated with an antagomir to miR-27a are more resistant to Mtb infection. Our findings reveal a strategy for Mtb to increase intracellular survival by manipulating the Ca2+-associated autophagy, and may also support the development of host-directed anti-TB therapeutic approaches.
PEDOT:PSS-based Multilayer Bacterial-Composite Films for Bioelectronics
Authors: Zajdel Tom J. , Baruch Moshe , Méhes Gábor , Stavrinidou Eleni , Berggren Magnus , Maharbiz Michel M. , Simon Daniel T. , Ajo-Franklin Caroline M. 
Published: October 2018

AbstractMicrobial electrochemical systems provide an environmentally-friendly means of energy conversion between chemical and electrical forms, with applications in wastewater treatment, bioelectronics, and biosensing. However, a major challenge to further development, miniaturization, and deployment of bioelectronics and biosensors is the limited thickness of biofilms, necessitating large anodes to achieve sufficient signal-to-noise ratios. Here we demonstrate a method for embedding an electroactive bacterium, Shewanella oneidensis MR-1, inside a conductive three-dimensional poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) matrix electropolymerized on a carbon felt substrate, which we call a multilayer conductive bacterial-composite film (MCBF). By mixing the bacteria with the PEDOT:PSS precursor in a flow-through method, we maintain over 90% viability of S. oneidensis during encapsulation. Microscopic analysis of the MCBFs reveal a tightly interleaved structure of bacteria and conductive PEDOT:PSS up to 80 µm thick. Electrochemical experiments indicate S. oneidensis in MCBFs can perform both direct and riboflavin-mediated electron transfer to PEDOT:PSS. When used in bioelectrochemical reactors, the MCBFs produce 20 times more steady-state current than native biofilms grown on unmodified carbon felt. This versatile approach to control the thickness of bacterial composite films and increase their current output has immediate applications in microbial electrochemical systems, including field-deployable environmental sensing and direct integration of microorganisms into miniaturized organic electronics.
High-Ranking Geladas Protect and Comfort Others After Conflicts
Authors: Palagi Elisabetta , Leone Alessia , Demuru Elisa , Ferrari Pier Francesco 
Published: October 2018

AbstractPost-conflict affiliation is a mechanism favored by natural selection to manage conflicts in animal groups thus avoiding group disruption. Triadic affiliation towards the victim can reduce the likelihood of redirection (benefits to third-parties) and protect and provide comfort to the victim by reducing its post-conflict anxiety (benefits to victims). Here, we test specific hypotheses on the potential functions of triadic affiliation inTheropithecus gelada, a primate species living in complex multi-level societies. Our results show that higher-ranking geladas provided more spontaneous triadic affiliation than lower-ranking subjects and that these contacts significantly reduced the likelihood of further aggression on the victim. Spontaneous triadic affiliation significantly reduced the victim’s anxiety (measured by scratching), although it was not biased towards kin or friends. In conclusion, triadic affiliation in geladas seems to be a strategy available to high-ranking subjects to reduce the social tension generated by a conflict. Although this interpretation is the most parsimonious one, it cannot be totally excluded that third parties could also be affected by the negative emotional state of the victim thus increasing a third party’s motivation to provide comfort. Therefore, the debate on the linkage between third-party affiliation and emotional contagion in monkeys remains to be resolved.
An interspecies barrier to tetraploid complementation and chimera formation
Authors: Yamaguchi Tomoyuki , Sato Hideyuki , Kobayashi Toshihiro , Kato-itoh Megumi , Goto Teppei , Hara Hiromasa , Mizuno Naoaki , Yanagida Ayaka , Umino Ayumi , Hamanaka Sanae , Suchy Fabian , Masaki Hideki , Ota Yasunori , Hirabayashi Masumi , Nakauchi Hiromitsu 
Published: October 2018

AbstractTo study development of the conceptus in xenogeneic environments, we assessed interspecies chimera formation as well as tetraploid complementation between mouse and rat. Overall contribution of donor PSC-derived cells was lower in interspecies chimeras than in intraspecies chimeras, and high donor chimerism was associated with anomalies or embryonic death. Organ to organ variation in donor chimerism was greater in interspecies chimeras than in intraspecies chimeras, suggesting species-specific affinity differences among interacting molecules necessary for organogenesis. In interspecies tetraploid complementation, embryo development was near normal until the stage of placental formation, after which no embryos survived.