bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic modification to induce CXCR2 overexpression in mesenchymal stem cells enhances treatment benefits in radiation-induced oral mucositis
Authors: Shen Zongshan , Wang Jiancheng , Huang Qiting , Shi Yue , Wei Zhewei , Zhang Xiaoran , Qiu Yuan , Zhang Min , Wang Yi , Qin Wei , Huang Shuheng , Huang Yinong , Liu Xin , Xia Kai , Zhang Xinchun , Lin Zhengmei 
Published: February 2018

AbstractRadiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting. By systematically evaluating the expression patterns of chemokines in radiation/chemical-induced oral mucositis, we found that CXCL2 was highly expressed, whereas cultured MSCs negligibly express the CXCL2 receptor CXCR2. Thus, we explored the potential therapeutic benefits of the transplantation of CXCR2-overexpressing MSCs (MSCsCXCR2) for mucositis treatment. Indeed, MSCsCXCR2 exhibited enhanced targeting ability to the inflamed mucosa in radiation/chemical-induced oral mucositis mouse models. Furthermore, we found that MSCCXCR2 transplantation accelerated ulcer healing by suppressing the production of pro-inflammatory chemokines and radiogenic reactive oxygen species (ROS). Altogether, these findings indicate that CXCR2 overexpression in MSCs accelerates ulcer healing, providing new insights into cell-based therapy for radiation/chemical-induced oral mucositis.
Rage induces hepatocellular carcinoma proliferation and sorafenib resistance by modulating autophagy
Authors: Li Jun , Wu Peng-Wen , Zhou Yuan , Dai Bo , Zhang Peng-Fei , Zhang Yu-Hen , Liu Yang , Shi Xiao-Lei 
Published: February 2018

AbstractThe receptor for advanced glycation end products (Rage) is involved in the development of various tumors and acts as an oncogenic protein. Rage is overexpressed in tumors including hepatocellular carcinoma (HCC). However, the molecular mechanism of Rage in HCC progression and sorafenib resistance remains unclear. In this study, enhanced Rage expression is highly associated proliferation and contributes to sorafenib resistance. Rage deficiency contributed to autophagy induction through activating AMPK/mTOR signaling pathway, which is important for sorafenib response. Moreover, the interactions between Rage and Rage ligands such as high mobility group box 1 (HMGB1) and s100a4 positively increased Rage expression. Our data indicate that Rage may be a potential target for therapeutic intervention in HCC and biomarker for sorafenib resistance.
NR4A2 protects cardiomyocytes against myocardial infarction injury by promoting autophagy
Authors: Liu Honghong , Liu Pingping , Shi Xingxing , Yin Deling , Zhao Jing 
Published: February 2018

AbstractMyocardial infarction (MI), characterized by ischemia-induced cardiomyocyte apoptosis, is the leading cause of mortality worldwide. NR4A2, a member of the NR4A orphan nucleus receptor family, is upregulated in mouse hearts with MI injury. Furthermore, NR4A2 knockdown aggravates heart injury as evidenced by enlarged hearts and increased apoptosis. To elucidate the underlying mechanisms of NR4A2-regulated apoptosis, we used H9c2 cardiomyocytes deprived of serum and neonatal rat cardiomyocytes (NRCMs) exposed to hypoxia to mimic ischemic conditions in vivo. As NR4A2 knockdown aggravates cardiomyocyte apoptosis, while NR4A2 overexpression ameliorates it, NR4A2 upregulation was considered an adaptive response to ischemia-induced cardiomyocyte apoptosis. By detecting changes in LC3 and using autophagy detection tools including Bafilomycin A1, 3MA and rapamycin, we found that NR4A2 knockdown promoted apoptosis through blocking autophagic flux. This apoptotic response was phenocopied by downregulation of NR4A2 after autophagic flux was impaired by Bafilomycin A1. Further study showed that NR4A2 binds to p53 directly and decreases its levels when it inhibits apoptosis; thus, p53/Bax is the downstream effector of NR4A2-mediated apoptosis, as previously reported. Changes in p53/Bax that were regulated by NR4A2 were also detected in injured hearts with NR4A2 knockdown. In addition, miR-212-3p is the upstream regulator of NR4A2, and it could downregulate the expression of NR4A2, as well as p53/Bax. The mechanism underlying the role of NR4A2 in apoptosis and autophagy was elucidated, and NR4A2 may be a therapeutic drug target for heart failure.
#2714, a novel active inhibitor with potent G2/M phase arrest and antitumor efficacy in preclinical models
Authors: Lu Wen-Jie , Peng Wen , Sun Qian-Qian , Li Yong-Huai , Chen Bo , Yu Luo-Ting , Xu You-Zhi , Wang Si-Ying , Zhao Ying-Lan 
Published: February 2018

AbstractArresting cell cycle has been one of the most common approaches worldwide in cancer therapy. Specifically, arresting cells in the G2/M phase is a promising therapeutic approach in the battle against lung cancer. In the present study, we demonstrated the anticancer activities and possible mechanism of compound #2714, which can prompt G2/M phase arrest followed by cell apoptosis induction in Lewis lung carcinoma LL/2 cells. In vitro, #2714 significantly inhibited LL/2 cell viability in a concentration- and time-dependent manner while exhibiting few toxicities on non-cancer cells. The mechanism study showed that cell proliferation inhibition due to the treatment with #2714 correlated with G2/M phase arrest and was followed by LL/2 cell apoptosis. The characterized changes were associated with the downregulation of phosphorylated cell division cycle 25C (Cdc25C) and upregulation of p53. Apoptosis-associated activation of cleaved caspase-3 was also detected. Moreover, #2714 strongly attenuated LL/2 cell proliferation by disrupting the phosphorylation of p44/42 mitogen-activated protein kinase (MAPK). In vivo, intraperitoneal administration of #2714 (25–100 mg/kg/day) to mice bearing established tumors in xenograft models significantly prevented LL/2 tumor growth (58.1%) without detectable toxicity. Compound #2714 significantly increased apoptosis in LL/2 lung cancer cells in mice models, as observed via terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, and the data from an immunohistochemical analysis showed that #2714 remarkably inhibited the proliferation and angiogenesis of lung cancer in vivo. Taken together, our data suggest that #2714 has a high potential anti-lung cancer efficacy with a pathway-specific mechanism of G2/M phase arrest and subsequent apoptosis induction both in vitro and in vivo; its potential to be an anticancer candidate warrants further investigation.
Oxidation-stable amine-containing adsorbents for carbon dioxide capture
Authors: Min Kyungmin , Choi Woosung , Kim Chaehoon , Choi Minkee 
Published: February 2018

AbstractAmine-containing solids have been investigated as promising adsorbents for CO2 capture, but the low oxidative stability of amines has been the biggest hurdle for their practical applications. Here, we developed an extra-stable adsorbent by combining two strategies. First, poly(ethyleneimine) (PEI) was functionalized with 1,2-epoxybutane, which generates tethered 2-hydroxybutyl groups. Second, chelators were pre-supported onto a silica support to poison p.p.m.-level metal impurities (Fe and Cu) that catalyse amine oxidation. The combination of these strategies led to remarkable synergy, and the resultant adsorbent showed a minor loss of CO2 working capacity (8.5%) even after 30 days aging in O2-containing flue gas at 110 °C. This corresponds to a ~50 times slower deactivation rate than a conventional PEI/silica, which shows a complete loss of CO2 uptake capacity after the same treatment. The unprecedentedly high oxidative stability may represent an important breakthrough for the commercial implementation of these adsorbents.
Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease
Authors: Idowu Jessica , Home Trisha , Patel Nisha , Magenheimer Brenda , Tran Pamela V. , Maser Robin L. , Ward Christopher J. , Calvet James P. , Wallace Darren P. , Sharma Madhulika 
Published: February 2018

AbstractPolycystic kidney disease (PKD) is a genetic disorder characterized by fluid-filled cysts in the kidney and liver that ultimately leads to end-stage renal disease. Currently there is no globally approved therapy for PKD. The Notch signaling pathway regulates cellular processes such as proliferation and de-differentiation, which are cellular hallmarks of PKD. Thus we hypothesized that the Notch pathway plays a critical role in PKD. Evaluation of protein expression of Notch signaling components in kidneys of Autosomal Recessive PKD (ARPKD) and Autosomal Dominant PKD (ADPKD) mouse models and of ADPKD patients revealed that Notch pathway members, particularly Notch3, were consistently upregulated or activated in cyst-lining epithelial cells. Notch3 expression correlated with rapidly growing cysts and co-localized with the proliferation marker, PCNA. Importantly, Notch inhibition significantly decreased forskolin-induced Notch3 activation and proliferation of primary human ADPKD cells, and significantly reduced cyst formation and growth of human ADPKD cells cultured in collagen gels. Thus our data indicate that Notch3 is aberrantly activated and facilitates epithelial cell proliferation in PKD, and that inhibition of Notch signaling may prevent cyst formation and growth.
The optimal movement patterns for mating encounters with sexually asymmetric detection ranges
Authors: Mizumoto Nobuaki , Dobata Shigeto 
Published: February 2018

AbstractAnimals have evolved various sex-specific characteristics to improve the efficiency of mating encounters. One is the sex-specific attracting signal. Signal receivers perform a combination of random search and navigation before and after signal detections. On the other hand, signal senders can also modify their movement patterns to optimize their encounter rates, which invokes a reverse side of random search problems that asks for the most efficient movement patterns of signal senders to be found by signal receivers. In this study, we focused on visual and auditory signals in particular, and quantified the efficiency of mating encounters of individual animals performing a Lévy walk, a special class of random walk, with a variety of speeds before signal detection. We found that signal senders should move more slowly and/or less diffusively than receivers to improve mating encounters. The optimal movement patterns of senders ranged from relatively slow to stationary ones depending on the density of individuals, the effective range of signals, and the ability of receivers to locate senders. By focusing on the optimal movement patterns of individuals that are often assumed to be given targets, the present study provides insights into strategies of effective attraction beyond the case of mate search.
Optogenetic Tractography for anatomo-functional characterization of cortico-subcortical neural circuits in non-human primates
Authors: Senova S. , Poupon C. , Dauguet J. , Stewart H. J. , Dugué G. P. , Jan C. , Hosomi K. , Ralph G. S. , Barnes L. , Drouot X. , Pouzat C. , Mangin J. F. , Pain F. , Doignon I. , Aron-Badin R. , Brouillet E. , Boyden E. S. , Mitrophanous K. A. , Hantraye P. , Palfi S. 
Published: February 2018

AbstractDissecting neural circuitry in non-human primates (NHP) is crucial to identify potential neuromodulation anatomical targets for the treatment of pharmacoresistant neuropsychiatric diseases by electrical neuromodulation. How targets of deep brain stimulation (DBS) and cortical targets of transcranial magnetic stimulation (TMS) compare and might complement one another is an important question. Combining optogenetics and tractography may enable anatomo-functional characterization of large brain cortico-subcortical neural pathways. For the proof-of-concept this approach was used in the NHP brain to characterize the motor cortico-subthalamic pathway (m_CSP) which might be involved in DBS action mechanism in Parkinson’s disease (PD). Rabies-G-pseudotyped and Rabies-G-VSVg-pseudotyped EIAV lentiviral vectors encoding the opsin ChR2 gene were stereotaxically injected into the subthalamic nucleus (STN) and were retrogradely transported to the layer of the motor cortex projecting to STN. A precise anatomical mapping of this pathway was then performed using histology-guided high angular resolution MRI tractography guiding accurately cortical photostimulation of m_CSP origins. Photoexcitation of m_CSP axon terminals or m_CSP cortical origins modified the spikes distribution for photosensitive STN neurons firing rate in non-equivalent ways. Optogenetic tractography might help design preclinical neuromodulation studies in NHP models of neuropsychiatric disease choosing the most appropriate target for the tested hypothesis.
Passively mode-locked interband cascade optical frequency combs
Authors: Bagheri Mahmood , Frez Clifford , Sterczewski Lukasz A. , Gruidin Ivan , Fradet Mathieu , Vurgaftman Igor , Canedy Chadwick L. , Bewley William W. , Merritt Charles D. , Kim Chul Soo , Kim Mijin , Meyer Jerry R. 
Published: February 2018

AbstractSince their inception, optical frequency combs have transformed a broad range of technical and scientific disciplines, spanning time keeping to navigation. Recently, dual comb spectroscopy has emerged as an attractive alternative to traditional Fourier transform spectroscopy, since it offers higher measurement sensitivity in a fraction of the time. Midwave infrared (mid-IR) frequency combs are especially promising as an effective means for probing the strong fundamental absorption lines of numerous chemical and biological agents. Mid-IR combs have been realized via frequency down-conversion of a near-IR comb, by optical pumping of a micro-resonator, and beyond 7 μm by four-wave mixing in a quantum cascade laser. In this work, we demonstrate an electrically-driven frequency comb source that spans more than 1 THz of bandwidth centered near 3.6 μm. This is achieved by passively mode-locking an interband cascade laser (ICL) with gain and saturable absorber sections monolithically integrated on the same chip. The new source will significantly enhance the capabilities of mid-IR multi-heterodyne frequency comb spectroscopy systems.
Consequences of VHL Loss on Global DNA Methylome
Authors: Robinson Claire M. , Lefebvre Francois , Poon Betty P. , Bousard Aurelie , Fan Xiaojun , Lathrop Mark , Tost Jorg , Kim William Y. , Riazalhosseini Yasser , Ohh Michael 
Published: February 2018

AbstractIn clear-cell renal cell carcinoma (ccRCC), loss of von Hippel-Lindau (VHL) tumour suppressor gene and reduced oxygen tension promote stabilisation of hypoxia-inducible factor (HIF) family of transcription factors, which promote changes in the expression of genes that contribute to oncogenesis. Multiple studies have demonstrated significant perturbations in DNA methylation in ccRCC via largely unclear mechanisms that modify the transcriptional output of tumour cells. Here, we show that the methylation status of the CpG dinucleotide within the consensus hypoxia-responsive element (HRE) markedly influences the binding of HIF and that the loss of VHL results in significant alterations in the DNA methylome. Surprisingly, hypoxia, which likewise promotes HIF stabilisation and activation, has relatively few effects on global DNA methylation. Gene expression analysis of ccRCC patient samples highlighted expression of a group of genes whose transcription correlated with methylation changes, including hypoxic responsive genes such as VEGF and TGF. These results suggest that the loss of VHL alters DNA methylation profile across the genome, commonly associated with and contributing to ccRCC progression.
Compensatory increases in tear volume and mucin levels associated with meibomian gland dysfunction caused by stearoyl-CoA desaturase-1 deficiency
Authors: Inaba Takaaki , Tanaka Yasuhisa , Tamaki Shusaku , Ito Tomotaka , Ntambi James M. , Tsubota Kazuo 
Published: February 2018

AbstractThe stearoyl-CoA desaturase (SCD) family of enzymes catalyzes monounsaturated fatty acid synthesis by inserting a cis double bond at the Δ9 position of saturated fatty acids. Disruption of these enzymes has been reported to induce a severe dry skin phenotype. Since lipid abnormalities in the meibomian glands have been associated with dry eye, we analyzed selected eye tissues contributing to tear volume and composition in genetically SCD-1-deficient mice (SCD-1 KO), including the lacrimal glands and conjunctiva. Previous histopathological analysis had revealed atrophy and loss of meibomian glands; taken together with the increased goblet cell and MUC5AC expression in the conjunctiva reported here, these findings suggest that the tear volume and mucin levels secreted are enhanced in the absence of lipid secretion as a compensatory mechanism. The expression of lipid metabolism genes in lacrimal glands was decreased in SCD1 KO mice. Thus, these results provide new pathophysiological mechanisms to pursue with regard to meibomian gland dysfunction. In addition, lack of SCD-1 causes a compensatory increase in the tear volume and mucin levels associated with changes in expression of lipid metabolism genes. These results may be useful as a new concept for dry eye treatment strategies.
Opportunistic random searcher versus intentional search image user
Authors: Garay József , Varga Zoltán , Móri Tamás F. , López Inmaculada , Gámez Manuel , Gallego Juan R. , Cabello Tomás 
Published: February 2018

AbstractWe consider two types of optimal foragers: a random searcher and a search image user. A search image user can find its desired prey with higher and undesired prey with lower probability than a random searcher. Our model considers the density-dependent travelling time and the time duration of reproduction (oviposition). In the framework of optimal foraging theory for one predator–two prey systems, we find that there are ranges of prey densities in which the search image user has a higher net energy intake, and there are other ranges of prey densities in which the random searcher has higher net energy intake. The damsel bug Nabis pseudoferus Remane (Hemiptera: Nabidae) is a generalist predator rather than an omnivore. This species has a wide range of arthropod prey (predominantly insects and mites). Several aspects of the biology of this species have been studied, especially its cannibalistic behaviour, which is a quite important feature because N. pseudoferus is often used as a biological control agent against lepidopteran pests in greenhouse crops. Experimentally, we found that Nabis is a search image user in the above sense.
Thermally Stable, High Performance Transfer Doping of Diamond using Transition Metal Oxides
Authors: Crawford Kevin G. , Qi Dongchen , McGlynn Jessica , Ivanov Tony G. , Shah Pankaj B. , Weil James , Tallaire Alexandre , Ganin Alexey Y. , Moran David A. J. 
Published: February 2018

AbstractWe report on optimisation of the environmental stability and high temperature operation of surface transfer doping in hydrogen-terminated diamond using MoO3 and V2O5 surface acceptor layers. In-situ annealing of the hydrogenated diamond surface at 400 °C was found to be crucial to enhance long-term doping stability. High temperature sheet resistance measurements up to 300 °C were performed to examine doping thermal stability. Exposure of MoO3 and V2O5 transfer-doped hydrogen-terminated diamond samples up to a temperature of 300 °C in ambient air showed significant and irreversible loss in surface conductivity. Thermal stability was found to improve dramatically however when similar thermal treatment was performed in vacuum or in ambient air when the oxide layers were encapsulated with a protective layer of hydrogen silsesquioxane (HSQ). Inspection of the films by X-ray diffraction revealed greater crystallisation of the MoO3 layers following thermal treatment in ambient air compared to the V2O5 films which appeared to remain amorphous. These results suggest that proper encapsulation and passivation of these oxide materials as surface acceptor layers on hydrogen-terminated diamond is essential to maximise their environmental and thermal stability.
Neural substrates of norm compliance in perceptual decisions
Authors: Toelch U. , Pooresmaeili A. , Dolan R. J. 
Published: February 2018

AbstractSocietal norms exert a powerful influence on our decisions. Behaviours motivated by norms, however, do not always concur with the responses mandated by decision relevant information potentially generating a conflict. To probe the interplay between normative and informational influences, we examined how prosocial norms impact on perceptual decisions subjects made in the context of a simultaneous presentation of social information. Participants displayed a bias in their perceptual decisions towards that mandated by social information. However, normative prescriptions modulated this bias bi-directionally depending on whether norms mandated a decision in accord or contrary to the contextual social information. At a neural level, the addition of a norms increased activity in prefrontal cortex and modulated functional connectivity between prefrontal and parietal areas. The bi-directional effect of our norms was captured by differential activations when participants decided against the social information. When norms indicated a decision in line with social information, non-compliance modulated lateral prefrontal cortex activity. By contrast, when norms mandated a decision against social information norm compliance increased activity in the anterior cingulate cortex. Hence, social norms changed the balance between a reliance on perceptual and social information by modulating brain activity in regions associated with response inhibition and conflict monitoring.
Hybridized Tungsten Oxide Nanostructures for Food Quality Assessment: Fabrication and Performance Evaluation
Authors: Kumar Pankaj , Sarswat Prashant K. , Free Michael L. 
Published: February 2018

AbstractTungsten oxide based micro and nanosized structures possess good capacitance as well as enhanced rate capability. Such properties are useful in various applications including electrochemical supercapacitors. Apart from supercapacitance, WO3and their 2D integrated structures have been modified using different methods to widen their range of the utility. Modification using layer coating, functionalization with other nanomaterial or molecules are methods that can be used to improve the core structure of WO3. But such modifications often alter electrochemical performance. The effects and outcomes of such modifications incorporated in WO3structures were studied using electrochemical methods, sensing behavior, and morphological examination. One goal for such modifications was to improve robustness of the WO3structures apart from any change in supercapacitance performance. After detailed electrochemical analyses of WO3structures, a preliminary study was performed regarding the feasibility of the WO3based sensors for food safety applications based on electrochemical detection of hazardous dyes in food. Preliminary results obtained after various electrochemical tests including pulsed voltammetry, cyclic voltammetry, and electrochemical impedance spectroscopy suggest the viability of WO3structures for food safety applications.