bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting surface deformation during mechanical attrition of metallic alloys
Authors: Cao Shan Cecilia , Zhang Xiaochun , Lu Jian , Wang Yongli , Shi San-Qiang , Ritchie Robert O. 
Published: March 2019

AbstractExtensive efforts have been devoted in both the engineering and scientific domains to seek new designs and processing techniques capable of making stronger and tougher materials. One such method for enhancing such damage-tolerance in metallic alloys is a surface nano-crystallization technology that involves the use of hundreds of small hard balls which are vibrated using high-power ultrasound so that they impact onto the surface of a material at high speed (termed Surface Mechanical Attrition Treatment or SMAT). However, few studies have been devoted to the precise underlying mechanical mechanisms associated with this technology and the effect of processing parameters. As SMAT is dynamic plastic deformation process, here we use random impact deformation as a means to investigate the relationship between impact deformation and the parameters involved in the processing, specifically ball size, impact velocity, ball density and kinetic energy. Using analytical and numerical solutions, we examine the size of the indents and the depths of the associated plastic zones induced by random impacts, with results verified by experiment in austenitic stainless steels. In addition, global random impact and local impact frequency models are developed to analyze the statistical characteristics of random impact coverage, together with a description of the effect of random multiple impacts, which are more reflective of SMAT. We believe that these models will serve as a necessary foundation for further, and more energy-efficient, development of such surface nano-crystalline processing technologies for the strengthening of metallic materials.
Copper transporter COPT5 participates in the crosstalk between vacuolar copper and iron pools mobilisation
Authors: Carrió-Seguí Àngela , Romero Paco , Curie Catherine , Mari Stéphane , Peñarrubia Lola 
Published: March 2019

AbstractCopper (Cu) deficiency affects iron (Fe) homeostasis in several plant processes, including the increased Fe requirements due to cuproprotein substitutions for the corresponding Fe counterpart. Loss-of-function mutants from Arabidopsis thaliana high affinity copper transporter COPT5 and Fe transporters NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN 3/4 (NRAMP3 and NRAMP4) were used to study the interaction between metals internal pools. A physiological characterisation showed that the copt5 mutant is sensitive to Fe deficiency, and that nramp3nramp4 mutant growth was severely affected under limiting Cu. By a transcriptomic analysis, we observed that NRAMP4 expression was highly induced in the copt5 mutant under Cu deficiency, while COPT5 was overexpressed in the nramp3nramp4 mutant. As a result, an enhanced mobilisation of the vacuolar Cu or Fe pools, when the other metal export through the tonoplast is impaired in the mutants, has been postulated. However, metals coming from internal pools are not used to accomplish the increased requirements that derive from metalloprotein substitution under metal deficiencies. Instead, the metal concentrations present in aerial parts of the copt5 and nramp3nramp4 mutants conversely show compensated levels of these two metals. Together, our data uncover an interconnection between Cu and Fe vacuolar pools, whose aim is to fulfil interorgan metal translocation.
Definition of a cell surface signature for human cardiac progenitor cells after comprehensive comparative transcriptomic and proteomic characterization
Authors: Torán José Luis , López Juan Antonio , Gomes-Alves Patricia , Aguilar Susana , Torroja Carlos , Trevisan-Herraz Marco , Moscoso Isabel , Sebastião Maria João , Serra Margarida , Brito Catarina , Cruz Francisco Miguel , Sepúlveda Juan Carlos , Abad José Luis , Galán-Arriola Carlos , Ibanez Borja , Martínez Fernando , Fernández María Eugenia , Fernández-Aviles Francisco , Palacios Itziar , R-Borlado Luis , Vázquez Jesús , Alves Paula M. , Bernad Antonio 
Published: March 2019

AbstractAdult cardiac progenitor/stem cells (CPC/CSC) are multipotent resident populations involved in cardiac homeostasis and heart repair. Assisted by complementary RNAseq analysis, we defined the fraction of the CPC proteome associable with specific functions by comparison with human bone marrow mesenchymal stem cells (MSC), the reference population for cell therapy, and human dermal fibroblasts (HDF), as a distant reference. Label-free proteomic analysis identified 526 proteins expressed differentially in CPC. iTRAQ analysis confirmed differential expression of a substantial proportion of those proteins in CPC relative to MSC, and systems biology analysis defined a clear overrepresentation of several categories related to enhanced angiogenic potential. The CPC plasma membrane compartment comprised 1,595 proteins, including a minimal signature of 167 proteins preferentially or exclusively expressed by CPC. CDH5 (VE-cadherin), OX2G (OX-2 membrane glycoprotein; CD200), GPR4 (G protein-coupled receptor 4), CACNG7 (calcium voltage-gated channel auxiliary subunit gamma 7) and F11R (F11 receptor; junctional adhesion molecule A; JAM-A; CD321) were selected for validation. Their differential expression was confirmed both in expanded CPC batches and in early stages of isolation, particularly when compared against cardiac fibroblasts. Among them, GPR4 demonstrated the highest discrimination capacity between all cell lineages analyzed.
Colloidal analogues of polymer chains, ribbons and 2D crystals employing orientations and interactions of nano-rods dispersed in a nematic liquid crystal
Authors: M Muhammed Rasi , Pujala Ravi Kumar , Dhara Surajit 
Published: March 2019

AbstractRobust control over the position, orientation and self-assembly of nonspherical colloids facilitate the creation of new materials with complex architecture that are important from technological and fundamental perspectives. We study orientation, elastic interaction and co-assembly of surface functionalized silica nano-rods in thin films of nematic liquid crystal. With homeotropic boundary condition, the nano-rods are predominantly oriented perpendicular to the nematic director which is different than the mostly parallel orientation of the micro-rods. The percentage of perpendicular nano-rods are significantly larger than the parallel nano-rods. The perpendicular nano-rods create very weak elastic deformation and exhibit unusual, out-of-plane, attractive interaction. On the other hand, the nano-rods oriented parallel to the director create strong elastic deformation and shows anisotropic, in-plane, dipolar interaction. In both orientations, the induced defects reside in the nano-rods. With the help of a dynamic laser tweezers and using nano-rods as building blocks we demonstrate colloidal analogues of linear polymer chains, ribbons and two-dimensional binary crystals.
Gadd45b mediates depressive-like role through DNA demethylation
Authors: Labonté Benoit , Jeong Yun Ha , Parise Eric , Issler Orna , Fatma Mena , Engmann Olivia , Cho Kyung-Ah , Neve Rachael , Nestler Eric J. , Koo Ja Wook 
Published: March 2019

AbstractAnimal studies using chronic social defeat stress (CSDS) in mice showed that brain-derived neurotrophic factor (BDNF) signaling in the mesolimbic dopamine (DA) circuit is important for the development of social aversion. However, the downstream molecular targets after BDNF release from ventral tegmental area (VTA) DA terminals are unknown. Here, we show that depressive-like behaviors induced by CSDS are mediated in part by Gadd45b downstream of BDNF signaling in the nucleus accumbens (NAc). We show that Gadd45b mRNA levels are increased in susceptible but not resilient mice. Intra-NAc infusion of BDNF or optical stimulation of VTA DA terminals in NAc enhanced Gadd45b expression levels in the NAc. Importantly, Gadd45b downregulation reversed social avoidance in susceptible mice. Together, these data suggest that Gadd45b in NAc contributes to susceptibility to social stress. In addition, we investigated the function of Gadd45b in demethylating CpG islands of representative gene targets, which have been associated with a depressive phenotype in humans and animal models. We found that Gadd45b downregulation changes DNA methylation levels in a phenotype-, gene-, and locus-specific fashion. Together, these results highlight the contribution of Gadd45b and changes in DNA methylation in mediating the effects of social stress in the mesolimbic DA circuit.
In vitro metabolic activation of vitamin D3 by using a multi-compartment microfluidic liver-kidney organ on chip platform
Authors: Theobald Jannick , Abu el Maaty Mohamed A. , Kusterer Nico , Wetterauer Bernhard , Wink Michael , Cheng Xinlai , Wölfl Stefan 
Published: March 2019

AbstractOrgan-on-chip platforms provide models that allow the representation of human physiological processes in cell-based miniaturized systems. Potential pre-clinical applications include drug testing and toxicity studies. Here we describe the use of a multi-compartment micro-fluidic chip to recapitulate hepatic vitamin D metabolism (vitamin D to 25-hydroxyvitamin D) and renal bio-activation (25-hydroxyvitamin D to 1,25-dihydroxyvitamin D) in humans. In contrast to cultivation in conventional tissue culture settings, on-chip cultivation of HepG2 and RPTEC cells in interconnected chambers, used to mimic the liver and kidneys, respectively, resulted in the enhanced expression of vitamin D metabolizing enzymes (CYP2R1, CYP27B1 and CYP24A1). Pump-driven flow of vitamin D3-containing medium through the microfluidic chip produced eluate containing vitamin D3 metabolites. LC-MSMS showed a strong accumulation of 25-hydroxyvitamin D. The chip eluate induced the expression of differentiation markers in HL-60 (acute myeloid leukemia) cells, assessed by qPCR and FACS analysis, in a manner similar to treatment with reference standards indicating the presence of fully activated 1,25 dihydroxyvitamin D, although the latter was not detected in the eluate by LC-MSMS. Interestingly, 25-hydroxyvitamin D by itself led to weak activation of HL-60 cells suggesting that 25-hydroxyvitamin D is also an active metabolite. Our experiments demonstrate that complex metabolic interactions can be reconstructed outside the human body using dedicated organ-on-chip platforms. We therefore propose that such systems may be used to mimic the in vivo metabolism of various micronutrients and xenobiotics.
Iron induces insulin resistance in cardiomyocytes via regulation of oxidative stress
Authors: Sung Hye Kyoung , Song Erfei , Jahng James Won Suk , Pantopoulos Kostas , Sweeney Gary 
Published: March 2019

AbstractIron overload is associated with various pathological changes which contribute to heart failure. Here, we examined mechanisms via which iron alters cardiomyocyte insulin sensitivity. Treatment of primary adult and neonatal cardiomyocytes as well as H9c2 cells with iron decreased insulin sensitivity determined via Western blotting or immunofluorescent detection of Akt and p70S6K phosphorylation and glucose uptake. Using CellROX deep red or DCF-DA probes we also observed that iron increased generation of reactive oxygen species (ROS), and that pretreatment with the superoxide dismutase mimetic MnTBAP reduced ROS production and attenuated iron-induced insulin resistance. SKQ1 and allopurinol but not apocynin reduced iron-induced ROS suggesting mitochondria and xanthine oxidase contribute to cellular ROS in response to iron. Western blotting for LC3-I, LC3-II and P62 levels as well as immunofluorescent co-detection of autophagosomes with Cyto-ID and lysosomal cathepsin activity indicated that iron attenuated autophagic flux without altering total expression of Atg7 or beclin-1 and phosphorylation of mTORC1 and ULK1. This conclusion was reinforced via protein accumulation detected using Click-iT HPG labelling after iron treatment. The adiponectin receptor agonist AdipoRon increased autophagic flux and improved insulin sensitivity both alone and in the presence of iron. We created an autophagy-deficient cell model by overexpressing a dominant-negative Atg5 mutant in H9c2 cells and this confirmed that reduced autophagy flux correlated with less insulin sensitivity. In conclusion, our study showed that iron promoted a cascade of ROS production, reduced autophagy and insulin resistance in cardiomyocytes.
Probing hair cell’s mechano-transduction using two-tone suppression measurements
Authors: Zhou Wenxiao , Nam Jong-Hoon 
Published: March 2019

AbstractWhen two sound tones are delivered to the cochlea simultaneously, they interact with each other in a suppressive way, a phenomenon referred to as two-tone suppression (2TS). This nonlinear response is ascribed to the saturation of the outer hair cell’s mechano-transduction. Thus, 2TS can be used as a non-invasive probe to investigate the fundamental properties of cochlear mechano-transduction. We developed a nonlinear cochlear model in the time domain to interpret 2TS data. The multi-scale model incorporates cochlear fluid dynamics, organ of Corti (OoC) mechanics and outer hair cell electrophysiology. The model simulations of 2TS show that the threshold amplitudes and rates of low-side suppression are dependent on mechano-transduction properties. By comparing model responses to existing 2TS measurement data, we estimate intrinsic characteristics of mechano-transduction such as sensitivity and adaptation. For mechano-transduction sensitivity at the basal location (characteristic frequency of 17 kHz) at 0.06 nm−1, the simulation results agree with 2TS measurements of basilar membrane responses. This estimate is an order of magnitude higher than the values observed in experiments on isolated outer hair cells. The model also demonstrates how the outer hair cell’s adaptation alters the temporal pattern of 2TS by modulating mechano-electrical gain and phase.
Methylmercury induces the expression of chemokine CCL4 via SRF activation in C17.2 mouse neural stem cells
Authors: Kim Min-Seok , Takahashi Tsutomu , Lee Jin-Yong , Toyama Takashi , Hoshi Takayuki , Kuge Shusuke , Fujiwara Yasuyuki , Naganuma Akira , Hwang Gi-Wook 
Published: March 2019

AbstractMethylmercury is an environmental pollutant that causes specific and serious damage to the central nervous system. We have previously shown that C-C motif chemokine ligand 4 (CCL4) protects cultured neural cells from methylmercury toxicity and expression of CCL4 is specifically induced in mouse brain by methylmercury. In this study, we examined the transcriptional regulatory mechanism that induces CCL4 expression by methylmercury using C17.2 mouse neural stem cells. The promoter region of the CCL4 gene was analyzed by a reporter assay, revealing that the region up to 50 bp upstream from the transcription start site was necessary for inducing expression of CCL4 by methylmercury. Nine transcription factors that might bind to this upstream region and be involved in the induction of CCL4 expression by methylmercury were selected, and the induction of CCL4 expression by methylmercury was suppressed by the knockdown of serum response factor (SRF). In addition, the nuclear level of SRF was elevated by methylmercury, and an increase in the amount bound to the CCL4 gene promoter was also observed. Furthermore, we examined the upstream signaling pathway involved in the induction of CCL4 expression by SRF, and confirmed that activation of p38 and ERK, which are part of the MAPK pathway, are involved. These results suggest that methylmercury induces the expression of CCL4 by activating SRF via the p38 and ERK signaling pathway. Our findings are important for elucidating the mechanism involved in the brain-specific induction of CCL4 expression by methylmercury.
PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer
Authors: Morihiro Toshiaki , Kuroda Shinji , Kanaya Nobuhiko , Kakiuchi Yoshihiko , Kubota Tetsushi , Aoyama Katsuyuki , Tanaka Takehiro , Kikuchi Satoru , Nagasaka Takeshi , Nishizaki Masahiko , Kagawa Shunsuke , Tazawa Hiroshi , Fujiwara Toshiyoshi 
Published: March 2019

AbstractWhile the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan–Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.
Crystal structure of dimeric Synechococcus spermidine synthase with bound polyamine substrate and product
Authors: Guédez Gabriela , Pothipongsa Apiradee , Sirén Saija , Liljeblad Arto , Jantaro Saowarath , Incharoensakdi Aran , Salminen Tiina A. 
Published: March 2019

Abstract
Spermidine is a ubiquitous polyamine synthesized by spermidine synthase (SPDS) from the substrates, putrescine and decarboxylated S-adenosylmethionine (dcAdoMet). SPDS is generally active as homodimer, but higher oligomerization states have been reported in SPDS from thermophiles, which are less specific to putrescine as the aminoacceptor substrate. Several crystal structures of SPDS have been solved with and without bound substrates and/or products as well as inhibitors. Here, we determined the crystal structure of SPDS from the cyanobacterium Synechococcus (SySPDS) that is a homodimer, which we also observed in solution. Unlike crystal structures reported for bacterial and eukaryotic SPDS with bound ligands, SySPDS structure has not only bound putrescine substrate taken from the expression host, but also spermidine product most probably as a result of an enzymatic reaction. Hence, to the best of our knowledge, this is the first structure reported with both amino ligands in the same structure. Interestingly, the gate-keeping loop is disordered in the putrescine-bound monomer while it is stabilized in the spermidine-bound monomer of the SySPDS dimer. This confirms the gate-keeping loop as the key structural element that prepares the active site upon binding of dcAdoMet for the catalytic reaction of the amine donor and putrescine.
Rat mRNA expression profiles associated with inhibition of ischemic acute kidney injury by losartan
Authors: Wu Yijin , Peng Wenying , Wei Ru , Zhou Yanhe , Fang Miaoxian , Liu Siyi , Deng Yujun , Yin Qi , Ouyang Xin , Hu Linhui , Hou Yating , Chen Chunbo 
Published: March 2019

AbstractObjective: Losartan was reported to inhibit the progression of acute kidney injury (AKI), but little is known about the underlying pharmacological mechanisms. In the present study, the mRNA expression profiles in ischemic AKI rat kidney altered by losartan treatment were analyzed by next-generation deep sequencing technology.Methods: Ischemia and reperfusion treatment was applied to induce AKI in Sprague–Dawley (SD) rats. The urea and creatinine contents in rat blood were measured. H&E staining was performed to evaluate the histological alteration of rat kidney tissues under a microscope. The TUNEL method was applied to analyze apoptosis in rat kidney tissues. The mRNA profiles in rat kidney were analyzed using next-generation deep sequencing. Differential gene expression was confirmed by quantitative qRT-PCR.Results: The rat model of AKI induced by ischemia and reperfusion showed significant increases in urea and creatinine levels, accompanied by a disrupted kidney tubular structure and renal cell apoptosis. Losartan treatment effectively inhibited the changes in urea and creatinine, tubular structure, and apoptosis in AKI rat kidney. A large number of mRNAs were found to be differentially expressed in the kidneys of AKI rats treated with losartan, which are involved in multiple processes and signaling pathways. The expression of nine differentially expressed genes such as monocyte chemoattractant protein-1 (CCL2) and suppressor of cytokine signaling 3 (SOCS3) was confirmed by qRT-PCR and Western blot.Conclusion: Losartan caused significant alterations in the gene expression profile in AKI rat kidney, which mediated its anti-AKI effects.
miR-500 promotes cell proliferation by directly targetting LRP1B in prostate cancer
Authors: Zhang Zhaoli , Cui Ran , Li Hui , Li Jinlong 
Published: March 2019

AbstractAccumulating evidence suggests that miRNAs play a crucial role in the development of prostate cancer (PC); however, the role of miR-500 in PC remains poorly understood. The data presented here reveal abnormal increases in miR-500 expression in PC tissues and cell lines. Suppression of miR-500 expression significantly inhibited the proliferation of PC-3 and LnCap cells and was negatively regulative with low-density lipoprotein receptor-related protein 1B (LRP1B). Increased cell cycle arrest at the G1 stage and decreased protein expression of cyclinD1 and CDK2 was observed in response to miR-500 knockdown in PC-3 and LnCap cells, in combination with LRP1B overexpression. LRP1B was identified as a target of miR-500 and was significantly decreased in PC tissues. Taken together, these findings demonstrate that miR-500 plays an important role in the proliferation of PC cells via the inhibition of LRP1B expression.
Entretien avec Éric Julliand : le psychiatre comme empêcheur de tourner en rond
Authors: Bachy Coralie , Frankhauser Adeline , Martin Brice 
Published: March 2019

Le psychiatre et psychanalyste lyonnais Éric Julliand accorde une interview dans laquelle il revient sur son parcours et ses principales conceptions de la psychiatrie.
Cet entretien est l’occasion de revenir sur les grandes évolutions de la psychiatrie publique de la seconde moitié du XXe siècle et le regard que porte Éric Julliand sur ses mutations contemporaines.