bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innovative methods to monitor rock and mountain slope deformation
Authors: Hormes Anne , Adams Marc , Amabile Anna Sara , Blauensteiner Franz , Demmler Christian , Fey Christine , Ostermann Marc , Rechberger Christina , Sausgruber Thomas , Vecchiotti Filippo , Vick Louise M. , Zangerl Christian 
Published: February 2020

AbstractDisplacement rates of mountain slope deformations that can affect entire valley mountain flanks are often measured spatially distributed in‐situ without spatial significance. The spatially explicit measurement and recording of time series of slope deformations is a challenge, as the unstable slopes are often disintegrated into several subdomains, which move with different deformation rates. The current state‐of‐the‐art monitoring systems detect slow to very slow deformation rates between mm/a and several m/a. Using the examples of slope deformations in Saalbach‐Hinterglemm and the deep rock slide Marzellkamm in Austria this paper presents the results of terrestrial laser scans, extensometer measurements, Spaceborne InSAR data, unmanned Aerial System Photogrammetry (UAS‐P), and fixed‐point measurements. The different measurements complement each other and are optimally aligned for different application areas. InSAR data can help to identify hot spots on regional and local scale, while UAS‐P enables for spatially high level accuracy in the detection of subdomains moving at different speeds. For local warning systems TLS, extensometers and GBInSAR deliver higher accuracy.
Endogenous opioid peptides and brain development: Endomorphin‐1 and Nociceptin play a sex‐specific role in the control of oligodendrocyte maturation and brain myelination
Authors: Mohamed Esraa , Paisley Caitlin E. , Meyer Logan C. , Bigbee John W. , Sato‐Bigbee Carmen 
Published: February 2020

AbstractThe generation of fully functional oligodendrocytes, the myelinating cells of the central nervous system, is preceded by a complex maturational process. We previously showed that the timing of oligodendrocyte differentiation and rat brain myelination were altered by perinatal exposure to buprenorphine and methadone, opioid analogs used for the management of pregnant addicts. Those observations suggested the involvement of the μ‐opioid receptor (MOR) and the nociceptin/orphanin FQ receptor (NOR). However, it remained to be determined if these receptors and their endogenous ligands could indeed control the timing of myelination under normal physiological conditions of brain development. We now found that the endogenous MOR ligand endomorphin‐1 (EM‐1) exerts a striking stimulatory action on cellular and morphological maturation of rat pre‐oligodendrocytes, but unexpectedly, these effects appear to be restricted to the cells from the female pups. Critically, this stimulation is abolished by coincubation with the endogenous NOR ligand nociceptin. Furthermore, NOR antagonist treatment of 9‐day‐old female pups results in accelerated brain myelination. Interestingly, the lack of sex‐dependent differences in developmental brain levels of EM‐1 and nociceptin, or oligodendroglial expression of MOR and NOR, suggests that the observed sex‐specific responses may be highly dependent on important intrinsic differences between the male and female oligodendrocytes. The discovery of a significant effect of EM‐1 and nociceptin in the developing female oligodendrocytes and brain myelination, underscores the need for further studies investigating brain sex‐related differences and their implications in opioid use and abuse, pain control, and susceptibility and remyelinating capacity in demyelinating disease as multiple sclerosis.
Lipopolysaccharide Reverses Hepatic Stellate Cell Activation Through Modulation of cMyb, Small Mothers Against Decapentaplegic, and CCAAT/Enhancer‐Binding Protein C/EBP Transcription Factors
Authors: Sharma Akanksha , Verma Alok K. , Kofron Matthew , Kudira Ramesh , Miethke Alexander , Wu Tong , Wang Jiang , Gandhi Chandrashekhar R. 
Published: February 2020

Background and Aims
During liver injury, quiescent hepatic stellate cells (qHSCs) transdifferentiate into proliferative and fibrogenic activated myofibroblastic phenotype (activated hepatic stellate cell; aHSCs) expressing smooth muscle α‐actin (αSMA) and platelet‐derived growth factor beta receptor (PDGFβR). Their interactions with gut‐derived bacterial lipopolysaccharide (LPS) are implicated in hepatic fibrogenesis. However, LPS can also attenuate fibrogenic characteristics of aHSCs.

Approach and Results
We examined molecular mechanisms of antifibrogenic effects of LPS on aHSCs in vitro and in vivo. Culture‐activated rat HSCs were exposed to 0‐100 ng/mL of LPS or its active component, diphosphoryl‐lipid A (DPLA), and parameters of fibrosis and inflammatory cytokines/chemokines were determined by qRT‐PCR, western, and immunohistochemical analyses. In vivo, HSCs were activated by repeated CCl4 administration to rats every 3 days for 3 or 8 weeks, then challenged with LPS (5 mg/kg; IP). HSCs were isolated 24 hours later, and fibrogenic/inflammatory parameters were analyzed. LPS induced phenotypic changes in aHSCs (rounding, size reduction) and loss of proliferation. LPS down‐regulated expression of αSMA, PDGFβR, transforming growth factor beta receptor 1 (TGFβR1), collagen 1α1 (Col1α1), and fibronectin while up‐regulating tumor necrosis factor alpha, interleukin‐6, and C‐X‐C motif chemokine ligand 1 expression. LPS did not increase peroxisome proliferation‐activated receptor gamma expression or lipid accumulation typical of qHSCs. DPLA elicited the same effects as LPS on aHSCs, indicating specificity, and monophosphoryl lipid A down‐regulated fibrogenic markers, but elicited very weak inflammatory response. LPS down‐regulated the expression of cMyb, a transcription factor for αSMA, and up‐regulated small mother against decapentaplegic (SMAD)7 and CCAAT/enhancer‐binding protein (C/EBP)δ, the transcriptional inhibitors of Col1α1 expression. In vivo LPS treatment of aHSCs inhibited their proliferation, down‐regulated PDGFβR, αSMA, TGFβR1, Col1α1, and cMyb expression, and increased expression of SMAD7, C/EBPα, and C/EBPδ.

Conclusions
In conclusion, LPS induces a unique phenotype in aHSCs associated with down‐regulation of key fibrogenic mechanisms and thus may have an important role in limiting fibrosis.
REACH Specific Environmental Release Categories for Plant Protection Product Applications
Authors: Dobe Christopher , Bonifay Sébastien , Krass Joachim D , McMillan Claire , Terry Adrian , Wormuth Matthias 
Published: February 2020

Abstract
The European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation requires that quantitative environmental risk assessment is carried out for hazardous substances used as coformulants in plant protection products (PPPs), if registered above 10 t/y. The European Crop Protection Association (ECPA) has developed generic exposure scenarios and specific environmental release categories (SpERCs) to support these risk assessments. The SpERCs offer refinements to the default release factors defined in environmental release categories (ERCs) and are intended to be used with nested multimedia mass balance models as part of the assessment of regional predicted environmental concentrations. Based on the application method of PPPs, 2 scenarios were defined for which SpERCs were developed: 1) spraying of PPPs and 2) direct application of granular products or treated seeds to soil. The SpERC for spray applications includes release factors to air and soil that depend on the vapor pressure of the coformulant. Calculations are presented to support the subSpERCs describing the transition from nonvolatile to volatile behavior. The most recent version of the spray application SpERC defines a release factor for surface water and more conservative release factors to soil compared with previous versions. Use of the ECPA SpERCs allows the coformulant emissions from PPPs to be fully accounted for in the regional-scale environmental risk assessment for a given substance, along with all other sources of emissions. Qualitative and quantitative justification for the ECPA-derived SpERCs is presented and serves as the background documentation to the online European Chemicals Agency (ECHA) SpERC factsheets. The approach developed here whereby regional-scale SpERCs are used in combination with a customized local-scale exposure model is potentially applicable for other sectors that are required to conduct exposure assessments outside the scope of the standard environmental REACH models. Integr Environ Assess Manag 2020;16:472–480. © 2020 Syngenta Crop Protection AG. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
Mechanistic Insights on the Formation of High‐Valent MnIII/IV=O Species Using Oxygen as Oxidant: A Theoretical Perspective
Authors: Sen Asmita , Vyas Nidhi , Pandey Bhawana , Jaccob Madhavan , Rajaraman Gopalan 
Published: February 2020

AbstractHigh‐valent metal−oxo species are of great interest as they serve as a robust catalyst for various organic transformations, and at the same time, they offer significant insight into the reactivity of various metalloenzymes. Formation of Mn−Oxo species is of great interest as they are involved in the Oxygen Evolving Complex of Photosystem II, and various bio‐mimic models were synthesized to understand its reactivity. In this context, using urea decorated amine ligands, Borovik et al. have reported the facile formation of MnIII=O and MnIV=O species from [MnIIH2buea]2− (here H2buea=tris[(N′‐tert‐butylureayl)‐N‐ethyl]amine) precursor complex using oxygen as the oxidant. While reactivity of these species is thoroughly studied, mechanism of formation of such species is scarcely explored. In this work, we have attempted to establish the formation of these species from the MnII precursor using the experimental conditions. Our calculations reveal the following fundamental steps in the formation of such species: i) O2 activation by MnII lead to formation of MnII−superoxide species wherein the oxidation state of the MnII found to be intact upon O2 binding facilitated by the deprotonated nitrogen atom present in the cavity (ii) in the second step, superoxo species is converted to MnII−hydroperoxo species, [MnIIH2buea(OOH)]2− using dimethylacetamide solvent as source for HAT reaction (iii) presence of water molecule found to aid the O−O bond cleavage in [MnIIH2buea(OOH)]2− species leading to the formation of the putative MnIII=O species, [MnIIIH3buea(O)]2− (iv) one‐electron oxidation of MnIII=O, leads to the formation of [MnIVH3buea(O)]− species and this step is endothermic and need some external oxidants for its formation. While various spin‐states and their roles are explored, our calculations reveal that the Mn atom prefers to be in the high‐spin state across the potential energy surface studied. However, the nature of the formation is strongly correlated to the spin state arising from the radical nature present in the O2 moiety and also in the deprotonated nitrogen atom. This offers a unique multistate reactivity channel for the formation these species easing various kinetic barriers across the potential energy surface. Further, we have also computed the spectral parameters for the experimentally observed species, which are in agreement with the reported data offering confidence on the mechanism established. To this end, our study unveils a facile formation of high‐valent Mn−Oxo species using O2 as oxidant and role of water molecules in the formation of such species, and these mechanistic insights are likely to have implications beyond the example studied here.
Heparin/poly‐l‐lysine nanoplatform with growth factor delivery for surface modification of cardiovascular stents: The influence of vascular endothelial growth factor loading
Authors: Tan Jianying , Cui Yuanyuan , Zeng Zheng , Wei Lai , Li Li , Wang Huanran , Hu Huiyi , Liu Tao , Huang Nan , Chen Junying , Weng Yajun 
Published: February 2020

AbstractThe rapid re‐endothelialization of the vascular stent surface is desirable for preventing thrombosis or reducing restenosis. Many biological factors that promote the biological behavior of endothelial cells have been used for the surface modification of stents. Vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, induces strong vascular growth. In this study, we investigated different VEGF concentrations (50 to 500 ng/ml) to determine the optimum concentration for biocompatibility. First, VEGF‐loaded heparin/poly‐l‐lysine (Hep‐PLL) nanoparticles were created by electrostatic interactions. Then, the VEGF‐loaded nanoparticles were immobilized on dopamine‐coated 316 L stainless steel (SS) surfaces. The physical and chemical properties of the modified surface were characterized and the biocompatibility was evaluated in vitro. The results indicated that the VEGF‐loaded nanoparticles were immobilized successfully on the 316LSS surface, as evidenced by the results of Alcian Blue staining and water contact angle (WCA) measurements. The low platelet adhesion and activation indicated that the modified surfaces had good blood compatibility. The modified surfaces showed a good inhibitory effect on smooth muscle cells, indicating that they inhibited tissue hyperplasia. In addition, the modified surfaces significantly promoted endothelial cell adhesion, proliferation, migration, and biological activity, especially VEGF concentration was 350 ng/ml (NPV350). The optical VEGF concentration of the surface modified Hep‐PLL nanoparticles was 350 ng/ml. The proposed method shows promise for potential applications for cardiovascular devices.
Evaluating the cytotoxicity of graphene oxide using embryonic stem cells‐derived cells
Authors: Hu Le , Fu Yan , Rong Liyuan , Yang Xinji , Li Yueyue , Wang Liqiang , Wu Wei 
Published: February 2020

AbstractGraphene oxide (GO) has several potential biomedical applications and therefore cytotoxic evaluation of GO is very important. However, the two most common in vitro models for testing cytotoxicity—primary human cells and immortalized cell lines—suffer serious limitations, namely limited supplies of cells and unrealistic cellular responses, respectively. Here, we demonstrate the use of embryonic stem cell (ESC)‐derived cells to study GO cytotoxicity. We tested the use of retinal pigment epithelium (RPE) cells derived from three‐dimensional human ESC cultures (“ESC‐RPE” cells) as a model of GO cytotoxicity by exposing them to varying concentrations of GO nanosheets. For comparison, we also performed the same test with primary human retinal pigment epithelium cells (“hRPE”), and with cells derived from a human RPE cell line (“ARPE19” cells). We found that cytotoxicity metrics (viability, apoptosis, intracellular reactive oxygen species, and mitochondrial membrane potential) were very similar in ESC‐RPE cells and hRPE cells, and those in ARPE19 cells were very different. We conclude that cell models of GO cytotoxicity derived from ESCs are an excellent alternative to primary human cells, without the limitations of tissue availability.
A positive feedback loop between Wnt/β‐catenin signaling and hTERT regulates the cancer stem cell‐like traits in radioresistant nasopharyngeal carcinoma cells
Authors: Chen Kaihua , Chen Li , Li Ling , Qu Song , Yu Binbin , Sun Yongchu , Wan Fangzhu , Chen Xishan , Liang Renba , Zhu Xiaodong 
Published: February 2020

AbstractRadioresistance may be induced by cancer stem cells (CSCs), while the biological traits of CSCs need to be retained by telomerase. The telomerase activity mainly depends on the transcriptional regulation of human telomerase reverse transcriptase (hTERT). Moreover, Wnt/β‐catenin signaling is also considered essential for maintaining the CSC phenotypes. In the previous study, we discovered that the radioresistant nasopharyngeal carcinoma cells CNE‐2R displayed CSC‐like traits, as well as high expression of hTERT and β‐catenin, but whether hTERT and β‐catenin were involved in regulating the CSC‐like traits and radiosensitivity of CNE‐2R cells remained unclear. In this study, our results suggested that hTERT could positively regulate the expression of CSC‐related proteins, as well as the cytoplasm‐ and nucleus‐β‐catenin, but it could not markedly regulate the expression of total β‐catenin in CNE‐2R cells. Meanwhile, Wnt/β‐catenin signaling had a positive regulatory effect on the expression of hTERT and CSC‐related proteins. Moreover, there was a β‐catenin/hTERT protein complex in CNE‐2R cells, indicating that β‐catenin could directly interact with hTERT protein. Our results also revealed that silencing hTERT or suppressing Wnt/β‐catenin signaling could attenuate telomerase activity and radioresistance of CNE‐2R cells; while suppressing Wnt/β‐catenin signaling, the telomerase activity and radioresistance could be reversed through overexpressing hTERT. Taken together, we have outlined a positive feedback loop between Wnt/β‐catenin signaling and hTERT in CNE‐2R cells, which can regulate the telomerase activity and CSC‐like traits, thus regulating the radiosensitivity. Therefore, blocking Wnt/β‐catenin signaling transduction and interfering with hTERT expression may be a promising approach for targeting radioresistant nasopharyngeal carcinoma cells with CSC‐like traits.
Inhibition of MAGEA2 regulates pluripotency, proliferation, apoptosis, and differentiation in mouse embryonic stem cells
Authors: Park Song , Han Jee Eun , Kim Hyeon‐Gyeom , Kim Hee‐Yeon , Kim Min‐Gi , Park Jin‐Kyu , Cho Gil‐Jae , Huang Hai , Kim Myoung Ok , Ryoo Zae Young , Han Se‐Hyeon , Choi Seong‐Kyoon 
Published: February 2020

AbstractMouse embryonic stem cells (mESCs) exhibit self‐renewal and pluripotency, can differentiate into all three germ layers, and serve as an essential model in stem cell research and for potential clinical application in regenerative medicine. Melanoma‐associated antigen A2 (MAGEA2) is not expressed in normal somatic cells but rather in different types of cancer, especially in undifferentiated cells, such as in the testis, differentiating cells, and ESCs. However, the role of MAGEA2 in mESCs remains to be clarified. Accordingly, in this study, we examined the expression and functions of MAGEA2 in mESCs. MAGEA2 messenger RNA (mRNA) expression was decreased during mESCs differentiation. MAGEA2 function was then evaluated in knockdown mESC. MAGEA2 knockdown resulted in decreased pluripotency marker gene expression in mESCs consequent to increased Erk1/2 phosphorylation. Decreased MAGEA2 expression inhibited mESC proliferation via S phase cell cycle arrest with a subsequent decrease in cell cycle‐associated genes Cdk1, Cdk2, Cyclin A1, Cyclin D1, and Cdc25a. Apoptotic mESCs markedly increased along with cleaved forms of caspases 3, 6, and 7 and PARP expression, confirming caspase‐dependent apoptosis. MAGEA2 knockdown significantly decreased embryoid body size in vitro when cells were differentiated naturally and teratoma size in vivo, concomitant with decreased ectoderm marker gene expression. These findings suggested that MAGEA2 regulates ESC pluripotency, proliferation, cell cycle, apoptosis, and differentiation. The enhanced understanding of the regulatory mechanisms underlying diverse mESC characteristics will facilitate the clinical application of mESCs.
microRNA expression profiles and the potential competing endogenous RNA networks in NELL‐1‐induced human adipose‐derived stem cell osteogenic differentiation
Authors: Yu Liyuan , Cen Xiao , Xia Kai , Huang Xinqi , Sun Wentian , Zhao Zhihe , Liu Jun 
Published: February 2020

AbstractStudies have indicated that Nel‐like molecule‐1 (NELL‐1) was an osteoblast‐specific cytokine and some specific microRNAs (miRNAs) could serve as competing endogenous RNA (ceRNA) to partake in osteogenic differentiation of human adipose‐derived stem cells (hASCs). The aim of this study was to explore the potential functional mechanisms of recombinant human NELL‐1 protein (rhNELL‐1) during hASCs osteogenic differentiation. rhNELL‐1 was added to osteogenic medium to activate osteogenic differentiation of hASCs. High‐throughput RNA sequencing (RNA‐Seq) was performed and validated by real‐time quantitative polymerase chain reaction. Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed to detect the functions of differentially expressed miRNAs and genes. Coding‐noncoding gene co‐expression network and ceRNA networks were constructed to predict the potential regulatory role of miRNAs. A total of 1010 differentially expressed miRNAs and 1762 differentially expressed messenger RNAs (mRNAs) were detected. miRNA‐370‐3p, bone morphogenetic protein 2 (BMP2), and parathyroid hormone like hormone (PTHLH) were differentially expressed during NELL‐1‐induced osteogenesis. Bioinformatic analyses demonstrated that these differentially expressed miRNAs and mRNAs enriched in Rap1 signaling pathway, PI3K‐Akt signaling pathway, p53 signaling pathway, Glucagon signaling pathway, and hypoxia‐inducible factor‐1 signaling pathway, which were important pathways related to osteogenic differentiation. In addition, miRNA‐370‐3p and has‐miR‐485‐5p were predicted to interact with circ0001543, circ0002405, and ENST00000570267 in ceRNA networks. Based on the gain or loss of functional experiments by transfection, the results showed that miR‐370‐3p was a key regulator in osteogenic differentiation by targeting BMP2 and disturbing the expression of PTHLH, and participated in NELL‐1‐stimulated osteogenesis. The present study provided the primary data and evidence for further exploration on the roles of miRNAs and ceRNAs during NELL‐1‐induced ossification of hASCs.
LINC02595 promotes tumor progression in colorectal cancer by inhibiting miR‐203b‐3p activity and facilitating BCL2L1 expression
Authors: Yang Zhidong , An Yue , Wang Ningning , Dong Xihua , Kang Hui 
Published: February 2020

AbstractColorectal cancer (CRC) is one of the most prevalent tumors worldwide. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators in postgenomic biology. Numerous lncRNAs have been identified as diagnostic biomarkers and therapeutic targets. However, the molecular mechanisms underlying the role of lncRNAs in CRC progression are not fully understood. Differentially expressed lncRNAs and messenger RNAs were investigated using a microarray approach in five paired primary CRC tumor tissues and the corresponding nontumor tissues and confirmed in an additional 116 paired tissues and 21 inflammatory bowel disease tissues and 15 adjacent normal tissues by a quantitative real‐time polymerase chain reaction. We also performed comprehensive transcriptome profiling analysis on Gene Expression Omnibus and The Cancer Genome Atlas datasets. We identified LINC02595 and evaluated its clinical significance as a plasma biomarker. The function of LINC02595 was evaluated using a panel of in vivo and vitro assays, including cell counting kit‐8, colony formation, cell cycle, apoptosis, RNA fluorescence in situ hybridization, luciferase reporter, immunohistochemistry, and CRC xenografts. We found that LINC02595 is upregulated in tumor tissues and blood samples of patients with CRC and CRC cell lines. Functional research found that LINC02595 promotes CRC cell growth, influences the cell cycle, and reduces apoptosis in vitro and vivo. Mechanistically, LINC02595 promoted BCL2‐like 1 (BCL2L1) expression through miR‐203b‐3p sponging. Our research demonstrated that LINC02595 is an oncogene in CRC and established the presence of a LINC02595‐miR‐203b‐BCL2L1 axis in CRC, which might provide a new diagnostic biomarker and therapeutic targets for the treatment of this disease.