bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways
Authors: Yang Lichao , Guo Han , Li Ying , Meng Xianglan , Yan Lu , Dan Zhang  , Wu Sangang , Zhou Hao , Peng Lu , Xie Qiang , Jin Xin 
Published: October 2016

AbstractThe present study aimed to examine the anti-inflammatory actions of oleoylethanolamide (OEA) in lipopolysaccharide (LPS)-induced THP-1 cells. The cells were stimulated with LPS (1 μg/ml) in the presence or absence of OEA (10, 20 and 40 μM). The pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. The THP-1 cells were transiently transfected with PPARα small-interfering RNA, and TLR4 activity was determined with a blocking test using anti-TLR4 antibody. Additionally, a special inhibitor was used to analyse the intracellular signaling pathway. OEA exerted a potent anti-inflammatory effect by reducing the production of pro-inflammatory cytokines and TLR4 expression, and by enhancing PPARα expression. The modulatory effects of OEA on LPS-induced inflammation depended on PPARα and TLR4. Importantly, OEA inhibited LPS-induced NF-κB activation, IκBα degradation, expression of AP-1, and the phosphorylation of ERK1/2 and STAT3. In summary, our results demonstrated that OEA exerts anti-inflammatory effects by enhancing PPARα signaling, inhibiting the TLR4-mediated NF-κB signaling pathway, and interfering with the ERK1/2-dependent signaling cascade (TLR4/ERK1/2/AP-1/STAT3), which suggests that OEA may be a therapeutic agent for inflammatory diseases.
On The Evolutionary Origin of Symbolic Communication
Authors: Grouchy Paul , D’Eleuterio Gabriele M. T. , Christiansen Morten H. , Lipson Hod 
Published: October 2016

AbstractThe emergence of symbolic communication is often cited as a critical step in the evolution of Homo sapiens, language, and human-level cognition. It is a widely held assumption that humans are the only species that possess natural symbolic communication schemes, although a variety of other species can be taught to use symbols. The origin of symbolic communication remains a controversial open problem, obfuscated by the lack of a fossil record. Here we demonstrate an unbroken evolutionary pathway from a population of initially noncommunicating robots to the spontaneous emergence of symbolic communication. Robots evolve in a simulated world and are supplied with only a single channel of communication. When their ability to reproduce is motivated by the need to find a mate, robots evolve indexical communication schemes from initially noncommunicating populations in 99% of all experiments. Furthermore, 9% of the populations evolve a symbolic communication scheme allowing pairs of robots to exchange information about two independent spatial dimensions over a one-dimensional channel, thereby increasing their chance of reproduction. These results suggest that the ability for symbolic communication could have emerged spontaneously under natural selection, without requiring cognitive preadaptations or preexisting iconic communication schemes as previously conjectured.
Structural and Functional Analysis of DDX41: a bispecific immune receptor for DNA and cyclic dinucleotide
Authors: Omura Hiroki , Oikawa Daisuke , Nakane Takanori , Kato Megumi , Ishii Ryohei , Ishitani Ryuichiro , Tokunaga Fuminori , Nureki Osamu 
Published: October 2016

AbstractIn the innate immune system, pattern recognition receptors (PRRs) specifically recognize ligands derived from bacteria or viruses, to trigger the responsible downstream pathways. DEAD box protein 41 (DDX41) is an intracellular PRR that triggers the downstream pathway involving the adapter STING, the kinase TBK1, and the transcription factor IRF3, to activate the type I interferon response. DDX41 is unique in that it recognizes two different ligands; i.e., double-stranded DNA (dsDNA) and cyclic dinucleotides (CDN), via its DEAD domain. However, the structural basis for the ligand recognition by the DDX41 DEAD domain has remained elusive. Here, we report two crystal structures of the DDX41 DEAD domain in apo forms, at 1.5 and 2.2 Å resolutions. A comparison of the two crystal structures revealed the flexibility in the ATP binding site, suggesting its formation upon ATP binding. Structure-guided functional analyses in vitro and in vivo demonstrated the overlapped binding surface for dsDNA and CDN, which is distinct from the ATP-binding site. We propose that the structural rearrangement of the ATP binding site is crucial for the release of ADP, enabling the fast turnover of DDX41 for the dsDNA/CDN-induced STING activation pathway.
CD4-mimetic sulfopeptide conjugates display sub-nanomolar anti-HIV-1 activity and protect macaques against a SHIV162P3 vaginal challenge
Authors: Ariën Kevin K. , Baleux Françoise , Desjardins Delphine , Porrot Françoise , Coïc Yves-Marie , Michiels Johan , Bouchemal Kawthar , Bonnaffé David , Bruel Timothée , Schwartz Olivier , Le Grand Roger , Vanham Guido , Dereuddre-Bosquet Nathalie , Lortat-Jacob Hugues 
Published: October 2016

AbstractThe CD4 and the cryptic coreceptor binding sites of the HIV-1 envelope glycoprotein are key to viral attachment and entry. We developed new molecules comprising a CD4 mimetic peptide linked to anionic compounds (mCD4.1-HS12 and mCD4.1-PS1), that block the CD4-gp120 interaction and simultaneously induce the exposure of the cryptic coreceptor binding site, rendering it accessible to HS12- or PS1- mediated inhibition. Using a cynomolgus macaque model of vaginal challenge with SHIV162P3, we report that mCD4.1-PS1, formulated into a hydroxyethyl-cellulose gel provides 83% protection (5/6 animals). We next engineered the mCD4 moiety of the compound, giving rise to mCD4.2 and mCD4.3 that, when conjugated to PS1, inhibited cell-free and cell-associated HIV-1 with particularly low IC50, in the nM to pM range, including some viral strains that were resistant to the parent molecule mCD4.1. These chemically defined molecules, which target major sites of vulnerability of gp120, are stable for at least 48 hours in conditions replicating the vaginal milieu (37 °C, pH 4.5). They efficiently mimic several large gp120 ligands, including CD4, coreceptor or neutralizing antibodies, to which their efficacy compares very favorably, despite a molecular mass reduced to 5500 Da. Together, these results support the development of such molecules as potential microbicides.
Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes
Authors: Nagaishi Kanna , Mizue Yuka , Chikenji Takako , Otani Miho , Nakano Masako , Konari Naoto , Fujimiya Mineko 
Published: October 2016

AbstractBone marrow-derived mesenchymal stem cells (MSCs) have contributed to the improvement of diabetic nephropathy (DN); however, the actual mediator of this effect and its role has not been characterized thoroughly. We investigated the effects of MSC therapy on DN, focusing on the paracrine effect of renal trophic factors, including exosomes secreted by MSCs. MSCs and MSC-conditioned medium (MSC-CM) as renal trophic factors were administered in parallel to high-fat diet (HFD)-induced type 2 diabetic mice and streptozotocin (STZ)-induced insulin-deficient diabetic mice. Both therapies showed approximately equivalent curative effects, as each inhibited the exacerbation of albuminuria. They also suppressed the excessive infiltration of BMDCs into the kidney by regulating the expression of the adhesion molecule ICAM-1. Proinflammatory cytokine expression (e.g., TNF-α) and fibrosis in tubular interstitium were inhibited. TGF-β1 expression was down-regulated and tight junction protein expression (e.g., ZO-1) was maintained, which sequentially suppressed the epithelial-to-mesenchymal transition of tubular epithelial cells (TECs). Exosomes purified from MSC-CM exerted an anti-apoptotic effect and protected tight junction structure in TECs. The increase of glomerular mesangium substrate was inhibited in HFD-diabetic mice. MSC therapy is a promising tool to prevent DN via the paracrine effect of renal trophic factors including exosomes due to its multifactorial action.
Dies1/VISTA expression loss is a recurrent event in gastric cancer due to epigenetic regulation
Authors: Oliveira Patrícia , Carvalho Joana , Rocha Sara , Azevedo Mafalda , Reis Inês , Camilo Vânia , Sousa Bárbara , Valente Sofia , Paredes Joana , Almeida Raquel , Huntsman David , Oliveira Carla 
Published: October 2016

AbstractDies1/VISTA induces embryonic stem-cell differentiation, via BMP-pathway, but also acts as inflammation regulator and immune-response modulator. Dies1 inhibition in a melanoma-mouse model led to increased tumour-infiltrating T-cells and decreased tumour growth, emphasizing Dies1 relevance in tumour-microenvironment. Dies1 is involved in cell de/differentiation, inflammation and cancer processes, which mimic those associated with Epithelial-to-Mesenchymal-Transition (EMT). Despite this axis linking Dies1 with EMT and cancer, its expression, modulation and relevance in these contexts is unknown. To address this, we analysed Dies1 expression, its regulation by promoter-methylation and miR-125a-5p overexpression, and its association with BMP-pathway downstream-effectors, in a TGFβ1-induced EMT-model, cancer cell-lines and primary samples. We detected promoter-methylation as a mechanism controlling Dies1 expression in our EMT-model and in several cancer cell-lines. We showed that the relationship between Dies1 expression and BMP-pathway effectors observed in the EMT-model, was not present in all cell-lines, suggesting that Dies1 has other cell-specific effectors, beyond the BMP-pathway. We further demonstrated that: Dies1 expression loss is a recurrent event in GC, caused by promoter methylation and/or miR-125a-5p overexpression and; GC-microenvironment myofibroblasts overexpress Dies1. Our findings highlight Dies1 as a novel player in GC, with distinct roles within tumour cells and in the tumour-microenvironment.
The 1257 Samalas eruption (Lombok, Indonesia): the single greatest stratospheric gas release of the Common Era
Authors: Vidal Céline M. , Métrich Nicole , Komorowski Jean-Christophe , Pratomo Indyo , Michel Agnès , Kartadinata Nugraha , Robert Vincent , Lavigne Franck 
Published: October 2016

AbstractLarge explosive eruptions inject volcanic gases and fine ash to stratospheric altitudes, contributing to global cooling at the Earth’s surface and occasionally to ozone depletion. The modelling of the climate response to these strong injections of volatiles commonly relies on ice-core records of volcanic sulphate aerosols. Here we use an independent geochemical approach which demonstrates that the great 1257 eruption of Samalas (Lombok, Indonesia) released enough sulphur and halogen gases into the stratosphere to produce the reported global cooling during the second half of the 13th century, as well as potential substantial ozone destruction. Major, trace and volatile element compositions of eruptive products recording the magmatic differentiation processes leading to the 1257 eruption indicate that Mt Samalas released 158 ± 12 Tg of sulphur dioxide, 227 ± 18 Tg of chlorine and a maximum of 1.3 ± 0.3 Tg of bromine. These emissions stand as the greatest volcanogenic gas injection of the Common Era. Our findings not only provide robust constraints for the modelling of the combined impact of sulphur and halogens on stratosphere chemistry of the largest eruption of the last millennium, but also develop a methodology to better quantify the degassing budgets of explosive eruptions of all magnitudes.
Dual Roles of IFN-γ and IL-4 in the Natural History of Murine Autoimmune Cholangitis: IL-30 and Implications for Precision Medicine
Authors: Syu Bi-Jhen , Loh Chia-En , Hsueh Yu-Hsin , Gershwin M. Eric , Chuang Ya-Hui 
Published: October 2016

AbstractPrimary biliary cirrhosis (PBC) is a progressive autoimmune liver disease with a long natural history. The pathogenesis of PBC is thought to be orchestrated by Th1 and/or Th17. In this study, we investigated the role of CD4+ helper T subsets and their cytokines on PBC using our previous established murine model of 2-OA-OVA immunization. We prepared adeno-associated virus (AAV)-IFN-γ and AAV-IL-4 and studied their individual influences on the natural history of autoimmune cholangitis in this model. Administration of IFN-γ significantly promotes recruitment and lymphocyte activation in the earliest phases of autoimmune cholangitis but subsequently leads to downregulation of chronic inflammation through induction of the immunosuppressive molecule IL-30. In contrast, the administration of IL-4 does not alter the initiation of autoimmune cholangitis, but does contribute to the exacerbation of chronic liver inflammation and fibrosis. Thus Th1 cells and IFN-γ are the dominant contributors in the initiation phase of this model but clearly may have different effects as the disease progress. In conclusion, better understanding of the mechanisms by which helper T cells function in the natural history of cholangitis is essential and illustrates that precision medicine may be needed for patients with PBC at various stages of their disease process.
Calcium dysregulation contributes to neurodegeneration in FTLD patient iPSC-derived neurons
Authors: Imamura Keiko , Sahara Naruhiko , Kanaan Nicholas M. , Tsukita Kayoko , Kondo Takayuki , Kutoku Yumiko , Ohsawa Yutaka , Sunada Yoshihide , Kawakami Koichi , Hotta Akitsu , Yawata Satoshi , Watanabe Dai , Hasegawa Masato , Trojanowski John Q. , Lee Virginia M.-Y. , Suhara Tetsuya , Higuchi Makoto , Inoue Haruhisa 
Published: October 2016

AbstractMutations in the gene MAPT encoding tau, a microtubules-associated protein, cause a subtype of familial neurodegenerative disorder, known as frontotemporal lobar degeneration tauopathy (FTLD-Tau), which presents with dementia and is characterized by atrophy in the frontal and temporal lobes of the brain. Although induced pluripotent stem cell (iPSC) technology has facilitated the investigation of phenotypes of FTLD-Tau patient neuronal cells in vitro, it remains unclear how FTLD-Tau patient neurons degenerate. Here, we established neuronal models of FTLD-Tau by Neurogenin2-induced direct neuronal differentiation from FTLD-Tau patient iPSCs. We found that FTLD-Tau neurons, either with an intronic MAPT mutation or with an exonic mutation, developed accumulation and extracellular release of misfolded tau followed by neuronal death, which we confirmed by correction of the intronic mutation with CRISPR/Cas9. FTLD-Tau neurons showed dysregulation of the augmentation of Ca2+ transients evoked by electrical stimulation. Chemogenetic or pharmacological control of neuronal activity-relevant Ca2+ influx by the introduction of designer receptors exclusively activated by designer drugs (DREADDs) or by the treatment with glutamate receptor blockers attenuated misfolded tau accumulation and neuronal death. These data suggest that neuronal activity may regulate neurodegeneration in tauopathy. This FTLD-Tau model provides mechanistic insights into tauopathy pathogenesis and potential avenues for treatments.
Multiple discrete soluble aggregates influence polyglutamine toxicity in a Huntington’s disease model system
Authors: Xi Wen , Wang Xin , Laue Thomas M. , Denis Clyde L. 
Published: October 2016

AbstractHuntington’s disease (HD) results from expansions of polyglutamine stretches (polyQ) in the huntingtin protein (Htt) that promote protein aggregation, neurodegeneration, and death. Since the diversity and sizes of the soluble Htt-polyQ aggregates that have been linked to cytotoxicity are unknown, we investigated soluble Htt-polyQ aggregates using analytical ultracentrifugation. Soon after induction in a yeast HD model system, non-toxic Htt-25Q and cytotoxic Htt-103Q both formed soluble aggregates 29S to 200S in size. Because current models indicate that Htt-25Q does not form soluble aggregates, reevaluation of previous studies may be necessary. Only Htt-103Q aggregation behavior changed, however, with time. At 6 hr mid-sized aggregates (33S to 84S) and large aggregates (greater than 100S) became present while at 24 hr primarily only mid-sized aggregates (20S to 80S) existed. Multiple factors that decreased cytotoxicity of Htt-103Q (changing the length of or sequences adjacent to the polyQ, altering ploidy or chaperone dosage, or deleting anti-aging factors) altered the Htt-103Q aggregation pattern in which the suite of mid-sized aggregates at 6 hr were most correlative with cytotoxicity. Hence, the amelioration of HD and other neurodegenerative diseases may require increased attention to and discrimination of the dynamic alterations in soluble aggregation processes.
A novel Al matrix composite reinforced by nano-AlNp network
Authors: Ma X. , Zhao Y. F. , Tian W. J. , Qian Z. , Chen H. W. , Wu Y. Y. , Liu X. F. 
Published: October 2016

AbstractIn pursuit of lightweighting of automobiles and low emission of transportation, the efforts to develop high-strength, heat-resistant and fatigue-resistant Al alloys and/or composites have been ongoing. Here we report a novel Al matrix composite with ultrahigh strength reinforced by a three dimensional network of nano-AlN particles for the first time. The in-situ synthesized AlN particles are connected by twinning bonding chains and built up a three dimensional network strengthening Al matrix enormously like the skeleton to human body. The composite containing 16.4wt.% AlN particles shows excellent properties: the ultimate tensile strengths can be up to 518MPa at room temperature and 190MPa at 350 °C. This peculiar performance results from the novel spatial distribution of nano-scale AlN particles. Our findings in this work would help to develop a potential candidate for high-performance heat resistance light-metal based materials.
Pathological Assessment of Rectal Cancer after Neoadjuvant Chemoradiotherapy: Distribution of Residual Cancer Cells and Accuracy of Biopsy
Authors: Xiao Lin , Yu Xin , Deng Wenjing , Feng Huixia , Chang Hui , Xiao Weiwei , Zhang Huizhong , Xi Shaoyan , Liu Mengzhong , Zhu Yujia , Gao Yuanhong 
Published: October 2016

AbstractWe investigated the distribution of residual cancer cells (RCCs) within different layers of the bowel wall in surgical specimens and the value of biopsies of primary rectal lesion after preoperative volumetric modulated arc therapy (VMAT) with concurrent chemotherapy in patients with rectal cancer. Between April 2011 and April 2013, 178 patients with rectal cancer who received preoperative VMAT, concurrent chemotherapy, and surgery were evaluated; 79 of the patients received a biopsy of the primary lesion after chemoradiotherapy and prior to surgery. The distribution of RCCs in the surgical specimens and the sensitivity and specificity of the biopsy of primary rectal lesions for pathological response were evaluated. Fifty-two patients had a complete pathological response in the bowel wall. Of the 120 patients with ypT2-4, the rate of detection of RCCs in the mucosa, submucosa, and muscularis propria was 20%, 36.7%, 69.2%, respectively. The sensitivity and specificity of biopsies of primary rectal lesions was 12.9% and 94.1%, respectively. After chemoradiotherapy, the RCCs were primarily located in the deeper layers of the bowel wall, and the biopsy results for primary rectal lesions were unreliable due to poor sensitivity.
Structurally Efficient Three-dimensional Metamaterials with Controllable Thermal Expansion
Authors: Xu Hang , Pasini Damiano 
Published: October 2016

AbstractThe coefficient of thermal expansion (CTE) of architected materials, as opposed to that of conventional solids, can be tuned to zero by intentionally altering the geometry of their structural layout. Existing material architectures, however, achieve CTE tunability only with a sacrifice in structural efficiency, i.e. a drop in both their stiffness to mass ratio and strength to mass ratio. In this work, we elucidate how to resolve the trade-off between CTE tunability and structural efficiency and present a lightweight bi-material architecture that not only is stiffer and stronger than other 3D architected materials, but also has a highly tunable CTE. Via a combination of physical experiments on 3D fabricated prototypes and numeric simulations, we demonstrate how two distinct mechanisms of thermal expansion appearing in a tetrahedron, can be exploited in an Octet lattice to generate a large range of CTE values, including negative, zero, or positive, with no loss in structural efficiency. The novelty and simplicity of the proposed design as well as the ease in fabrication, make this bi-material architecture well-suited for a wide range of applications, including satellite antennas, space optical systems, precision instruments, thermal actuators, and MEMS.
Synergistic Communication between CD4+ T Cells and Monocytes Impacts the Cytokine Environment
Authors: Schrier Sarah B. , Hill Abby S. , Plana Deborah , Lauffenburger Douglas A. 
Published: October 2016

AbstractPhysiological cytokine environments arise from factors produced by diverse cell types in coordinated concert. Understanding the contributions of each cell type in the context of cell-cell communication is important for effectively designing disease modifying interventions. Here, we present multi-plexed measurement of 48 cytokines from a coculture system of primary human CD4+ T cells and monocytes across a spectrum of stimuli and for a range of relative T cell/monocyte compositions, coupled with corresponding measurements from PBMCs and plasma from the same donors. Computational analysis of the resulting data-sets elucidated communication-independent and communication-dependent contributions, including both positive and negative synergies. We find that cytokines in cell supernatants were uncorrelated to those found in plasma. Additionally, as an example of positive synergy, production levels of CXCR3 cytokines IP-10 and MIG, depend non-linearly on both IFNγ and TNFα levels in cross-talk between T cells and monocytes. Overall, this work demonstrates that communication between cell types can significantly impact the consequent cytokine environment, emphasizing the value of mixed cell population studies.
Mu rhythm suppression reflects mother-child face-to-face interactions: a pilot study with simultaneous MEG recording
Authors: Hasegawa Chiaki , Ikeda Takashi , Yoshimura Yuko , Hiraishi Hirotoshi , Takahashi Tetsuya , Furutani Naoki , Hayashi Norio , Minabe Yoshio , Hirata Masayuki , Asada Minoru , Kikuchi Mitsuru 
Published: October 2016

AbstractSpontaneous face-to-face interactions between mothers and their children play crucial roles in the development of social minds; however, these inter-brain dynamics are still unclear. In this pilot study, we measured MEG mu suppression during face-to-face spontaneous non-linguistic interactions between mothers and their children with autism spectrum disorder (ASD) using the MEG hyperscanning system (i.e., simultaneous recording). The results demonstrated significant correlations between the index of mu suppression (IMS) in the right precentral area and the traits (or severity) of ASD in 13 mothers and 8 children (MEG data from 5 of the children could not be obtained due to motion noise). In addition, higher IMS values (i.e., strong mu suppression) in mothers were associated with higher IMS values in their children. To evaluate the behavioral contingency between mothers and their children, we calculated cross correlations between the magnitude of the mother and child head-motion during MEG recordings. As a result, in mothers whose head motions tended to follow her child’s head motion, the magnitudes of mu suppression in the mother’s precentral area were large. Further studies with larger sample sizes, including typically developing children, are necessary to generalize this result to typical interactions between mothers and their children.