bluuebunny/crossref_metadata_2025_split huggingface dataset:
New generation CPPs show distinct selectivity for cancer and noncancer cells
Authors: Tansi Felista L. , Filatova Margarita P. , Koroev Dmitri O. , Volpina Olga M. , Lange Steffi , Schumann Christina , Teichgräber Ulf K. , Reissmann Siegmund , Hilger Ingrid 
Published: October 2018

AbstractIn the last three decades, many new cell‐penetrating peptides (CPPs) were developed that exhibited enhanced cell selectivity. Thus, we aimed to validate the tumor cell selectivity of peptides from this new generation, namely fragments mini‐crotamine and mini‐maurocalcine. Both of these peptides are derived from venoms. Furthermore, we studied an analog of the classical CPP HIV‐TAT(47‐57) with alternating chirality of Arg residues. To allow covalent coupling of cargoes or fluorophores, a cysteine residue was introduced to the N‐terminus of the synthesized peptides. The therapeutic antibody trastuzumab conjugated to different fluorescent dyes was used for internalization studies. Comparison of uptake efficiencies revealed that CPPs of the new generation are in contrast to MPG‐peptides, nearly unable to internalize the noncovalently formed complexes with trastuzumab. Interestingly, the fluorescent derivative of the crotamine fragment was mainly observed in a subpopulation of breast cancer cells, whereas it was homogenously distributed in fibrosarcoma, colon cancer, and noncancerous endothelia cells. Thus, the fluorescent crotamine fragment reported herein is a potent theranostic tool for image‐guided applications. This peptide can be used to pinpoint the level of heterogeneity present within tumors and aid in the generation of therapeutics that target heterogenic subpopulations.
Lysophosphatidic acid induces the crosstalk between the endovascular human trophoblast and endothelial cells in vitro
Authors: Beltrame Jimena S. , Scotti Leopoldina , Sordelli Micaela S. , Cañumil Vanesa A. , Franchi Ana M. , Parborell Fernanda , Ribeiro María L. 
Published: October 2018

AbstractSpiral artery remodeling at the maternal–fetal interface is crucial for successful pregnancy and requires the interaction between the first trimester trophoblast and the endothelial cells of the maternal vessels. However, the precise mechanism of this dialog has yet to be determined. The current study investigated whether lysophosphatidic acid (LPA) modulates trophoblast–endothelial crosstalk in vitro. HTR‐8/SVneo trophoblast cell line (H8) was seeded on top of Geltrex, incubated with LPA or LPA + NS‐398 (selective cyclooxygenase‐2 inhibitor), LPA + 1400W (selective inducible nitric oxide synthase inhibitor) or LPA + IL‐6 neutralizing antibody and assayed for tube formation to model the acquisition of trophoblast endovascular phenotype. The supernatants were collected and used as conditioned media (CM). To test trophoblast–endothelial crosstalk, the endothelial cell line EA.hy926 was incubated with trophoblast CM. The CM from LPA‐induced tubulogenesis stimulated endothelial cells migration and did not modify the apoptosis. Soluble factors derived from cyclooxygenase‐2 and IL‐6 pathways were involved in H8–EA.hy926 interaction under the LPA effect. Moreover, LPA increased the levels of IL‐6 mRNA by cyclooxygenase‐2 pathway in H8 cells. Collectively, LPA promotes trophoblast–endothelial crosstalk in vitro and induces the release of trophoblast soluble factors that stimulate endothelial cells migration without changes in apoptosis. The evidence presented here provides new insights about an active role of LPA as a lipid mediator regulating vascular remodeling at the maternal–fetal interface.
Real‐time detection of breast cancer at the cellular level
Authors: Carver Gary E. , Locknar Sarah A. , Weaver Donald L. , Stein Janet L. , Stein Gary S. 
Published: October 2018

AbstractNovel optoelectronic instrumentation has been developed for the multispectral imaging of autofluorescence emitted by metabolic fluorophores. The images resolve individual cells while spectra are collected for each pixel in the images. These datacubes are generated at a rate of 10 per second—fast enough for surgical guidance. The data is processed in real time to provide a single color‐coded image to the surgeon. To date, the system has been applied to fresh, ex vivo, human surgical specimens and has distinguished breast cancer from benign tissue. The approach is applicable to in vivo measurements of surgical margins and needle‐based optical biopsies. Ongoing work demonstrates that the system has great potential for translation to a hand‐held probe with high sensitivity and specificity.
PURB is a positive regulator of amino acid‐induced milk synthesis in bovine mammary epithelial cells
Authors: Huo Nan , Yu Mengmeng , Li Xueying , Zhou Chenjian , Jin Xin , Gao Xuejun 
Published: October 2018

AbstractPrevious studies have implicated that purine‐rich element binding protein B (PURB) is a key regulator of gene transcription and cell physiology. Whether PURB plays a regulatory role in milk synthesis in bovine mammary epithelial cells (BMECs) is not known. We observed that Met and Leu increased PURB expression and nuclear localization. Overexpression of PURB led to increased milk protein and fat synthesis as well as mTOR and SREBP‐1c expression whereas PURB knockdown had the opposite effects. The PI3K inhibitor wortmannin totally abolished the stimulation of Met and Leu on PURB expression, and we further confirmed that PURB was required for Met and Leu to stimulate mTOR phosphorylation and SREBP‐1c expression. We also demonstrated that PURB binds to the promoters of mTOR and SREBP‐1c, and these bindings were increased by Met and Leu stimulation. In summary, our data reveal that PURB is required for amino acids to stimulate mTOR and SREBP‐1c gene expression, and PURB is a positive regulator of amino acid‐induced PI3K‐regulated milk protein and fat synthesis in BMECs.
Identification of CD28 and PTEN as novel prognostic markers for cervical cancer
Authors: Shen Fujin , Zheng Hongyun , Zhou Limei , Li Wei , Liu Juan , Xu Xuexian 
Published: October 2018

AbstractCervical cancer (CC) is the most common malignant tumor with poor clinical outcome among women. Identification of novel biomarkers could be beneficial for the clinical diagnosis and treatment of CC. This study aimed to identify prognostic biomarkers for the prediction of prognostic status of CC patients, and explore the effect of the corresponding methylated genes in the occurrence and development of CC. The methylation microarray data of CC was extracted from The Cancer Genome Atlas (TCGA) dataset. The methylation genes associated with the prognostic status were identified based on the information of the relapse‐free survival (RFS) of the CC patients. The prognostic gene pairs were further identified. Then, the prognostic signature was identified by the forward search algorithm based on the C‐index method. The results were validated by independent dataset. Finally, the functional analysis was performed on the methylation genes. A total of 276 methylation genes and 2508 gene pairs associated with the prognostic status of the CC were identified. A signature composed of eight methylation gene pairs was obtained to predict the prognostic status of cervical patients. A series of genes that played an important role in the occurrence and development of CC were obtained by the functional enrichment analysis. To summary, a prognostic signature consisting of eight methylation gene pairs was obtained. Of note, the
CD28 and
PTEN gene pair were found to play important roles in the occurrence and development of CC.
CRISPR–Cas9 in genome editing: Its function and medical applications
Authors: Khadempar Saedeh , Familghadakchi Shokoufeh , Motlagh Roozbeh Akbari , Farahani Najmeh , Dashtiahangar Maryam , Rezaei Hamzeh , Gheibi Hayat Seyed Mohammad 
Published: October 2018

AbstractThe targeted genome modification using RNA‐guided nucleases is associated with several advantages such as a rapid, easy, and efficient method that not only provides the manipulation and alteration of genes and functional studies for researchers, but also increases their awareness of the molecular basis of the disease and development of new and targeted therapeutic approaches. Different techniques have been emerged so far as the molecular scissors mediating targeted genome editing including zinc finger nuclease, transcription activator‐like effector nucleases, and clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR‐associated protein 9 (Cas9). CRISPR–Cas9 is a bacterial immune system against viruses in which the single‐strand RNA‐guided Cas9 nuclease is linked to the targeted complementary sequences to apply changes. The advances made in the transfer, modification, and emergence of specific solutions have led to the creation of different classes of CRISPR–Cas9. Since this robust tool is capable of direct correction of disease‐causing mutations, its ability to treat genetic disorders has attracted the tremendous attention of researchers. Considering the reported cases of nonspecific targeting of Cas9 proteins, many studies focused on enhancing the Cas9 features. In this regard, significant advances have been made in choosing guide RNA, new enzymes and methods for identifying misplaced targeting. Here, we highlighted the history and various direct aspects of CRISPR–Cas9, such as precision in genomic targeting, system transfer and its control over correction events with its applications in future biological studies, and modern treatment of diseases.
MiR‐448‐5p inhibits TGF‐β1‐induced epithelial‐mesenchymal transition and pulmonary fibrosis by targeting Six1 in asthma
Authors: Yang Zhao‐Chuan , Qu Zheng‐Hai , Yi Ming‐Ji , Shan Yan‐Chun , Ran Ni , Xu Lei , Liu Xin‐Jie 
Published: October 2018

AbstractMicroRNAs (miRNAs) are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation. The aim of this study was to explore how miR‐448‐5p affects airway remodeling and transforming growth factor‐β1 (TGF‐β1)‐stimulated epithelial‐mesenchymal transition (EMT) by targeting Sine oculis homeobox homolog 1 (Six1) in asthma. Asthmatic mice models with airway remodeling were induced with ovalbumin solution. MiRNA expression was evaluated using quantitative real‐time polymerase chain reaction. Transfection studies of bronchial epithelial cells were performed to determine the target genes. A luciferase reporter assay system was applied to identify whether Six1 is a target gene of miR‐448‐5p. In the current study, we found that miR‐448‐5p was dramatically decreased in lung tissues of asthmatic mice and TGF‐β1‐stimulated bronchial epithelial cells. In addition, the decreased level of miR‐448‐5p was closely associated with the increased expression of Six1. Overexpression of miR‐448‐5p decreased Six1 expression and, in turn, suppressed TGF‐β1‐mediated EMT and fibrosis. Next, we predicted that Six1 was a potential target gene of miR‐448‐5p and demonstrated that miR‐448‐5p could directly target Six1. An SiRNA targeting Six1 was sufficient to suppress TGF‐β1‐induced EMT and fibrosis in 16HBE cells. Furthermore, the overexpression of Six1 partially reversed the protective effect of miR‐448‐5p on TGF‐β1‐mediated EMT and fibrosis in bronchial epithelial cells. Taken together, the miR‐448‐5p/TGF‐β1/Six1 link may play roles in the progression of EMT and pulmonary fibrosis in asthma.
The role of iron metabolism in cancer therapy focusing on tumor‐associated macrophages
Authors: Dong Dandan , Zhang Gejing , Yang Jiancheng , Zhao Bin , Wang Shenghang , Wang Luyao , Zhang Ge , Shang Peng 
Published: October 2018

AbstractIron is an essential micronutrient in mammalian cells for basic processes such as DNA synthesis, cell cycle progression, and mitochondrial activity. Macrophages play a vital role in iron metabolism, which is tightly linked to their phagocytosis of senescent and death erythrocytes. It is now recognized that the polarization process of macrophages determines the expression profile of genes associated with iron metabolism. Although iron metabolism is strictly controlled by physiology, cancer has recently been connected with disordered iron metabolism. Moreover, in the environment of cancer, tumor‐associated macrophages (TAMs) exhibit an iron release phenotype, which stimulates tumor cell survival and growth. Usually, the abundance of TAMs in the tumor is implicated in poor disease prognosis. Therefore, important attention has been drawn toward the development of tumor immunotherapies targeting these TAMs focussing on iron metabolism and reprogramming polarized phenotypes. Although further systematic research is still required, these efforts are almost certainly valuable in the search for new and effective cancer treatments.
Overexpression of cancer susceptibility candidate 2 inhibited progression of hepatocellular carcinoma cells
Authors: Gao Xiang , Du Haijun , Zhang Ruoxi , Li Cong , Wang Hongguang , Xuan Qi , Liu Diangang 
Published: October 2018

AbstractObjectiveOur study was aimed to investigate the effect of cancer susceptibility candidate 2 (CASC2) on the proliferation, cell cycle, apoptosis, and metastasis of hepatocellular carcinoma (HCC) cells.MethodsCASC2 expression in tumor tissues and HCC cells was tested by quantitative real‐time polymerase chain reaction. After manipulating the expression of CASC2 in Hep3B and HepG2 cells, cells viability, including proliferation, apoptosis, cell‐cycle distribution, migration, and invasion were examined by colony formation assay, flow cytometry, wound‐healing assay, and transwell assay, respectively. The expression levels of proteins associated with the cell cycle and AKT/mTOR pathway were measured by the western blot. Stably transfected HepG2 cells were used to construct nude mice models, and tumorigenesis was evaluated to investigate the in vivo functions of CASC2 in HCC progression.ResultsIn tissues and cells of HCC, decreased CASC2 expressions were confirmed. Overexpression of CASC2 made cell cycle stagnated at G0/G1 phase and induced apoptosis. Meanwhile, the overexpression of CASC2 played significant roles in inhibiting the proliferation, migration, and invasion of HCC cells. Furthermore, In vivo experiment indicated that CASC2 restrained the growth of tumors.ConclusionOur study suggested that CASC2 promoted cell apoptosis and suppressed cell growth and metastasis in HCC, indicating that CASC2 might be a useful biomarker of HCC.
Overexpressed circ_0067934 acts as an oncogene to facilitate cervical cancer progression via the miR‐545/EIF3C axis
Authors: Hu Chunjie , Wang Yue , Li Ao , Zhang Jin , Xue Fangfang , Zhu Li 
Published: October 2018

AbstractCircular RNAs were recently identified as a novel type of noncoding RNAs. An increasing number of reports have demonstrated their essential regulatory roles in various biological processes and human diseases, including cancer. However, the role of circRNA in cervical cancer (CC) remains largely unknown. In the current study, we investigated the physiological functions of circ_0067934 during CC development and progression. We found that circ_0067934 was overexpressed in CC tissues and cell lines. Circ_0067934 upregulation was associated with advanced stage, lymph node metastasis, and poor prognosis in CC patients. Knockdown of circ_0067934 suppressed the proliferation, colony formation, migration, invasion, and epithelial‐mesenchymal transition of CC cells in vitro. Circ_0067934 loss also inhibited CC tumor growth in vivo. Mechanistically, silencing circ_0067934 increased miR‐545 expression. MiR‐545 repressed EIF3C expression through targeting its 3′‐untranslated region. MiR‐545 suppressed the proliferation, migration, and invasion of CC cells, whereas restoration of EIF3C could rescue the effects of circ_0067934 knockdown. Taken together, our findings revealed that circ_0067934 promotes CC progression via miR‐545/EIF3C axis. Our study may provide a new insight into the pathogenesis of CC.
Effects of sound elements on growth, viability and protein production yield in Escherichia coli
Authors: Acuña‐González Edgar , Ibarra David , Benavides Jorge 
Published: October 2018

AbstractBACKGROUNDThe effect of sound on biological systems has been addressed previously in the literature. However, most studies addressing this topic focus on the characterization of the effect of frequency on biological systems. In this regard the effect of other soundwave elements has been overlooked. In the present work, the effects of frequency, amplitude, duration, intermittence and pulse – individually and in combination – were tested with Escherichia coli by measuring biomass, viability and recombinant production yield, generating a deeper understanding of the effect of sound on bacterial systems.RESULTSFrequency and duration treatments influenced biomass concentration, increasing its value 19% and 44%, respectively, when compared with the standard treatment at time 24 h. However, such treatments showed high variability. Amplitude had a significant effect on biomass viability, doubling the duration of the exponential phase. Concerning protein production, intermittence increased the yield of recombinant protein 1.5 times without the contribution of any other sound element.CONCLUSIONSIt was established that intermittence and amplitude have a relevant role in protein production yield and viability, respectively. Other sound elements such as frequency and duration seem to have effect on biomass concentration, although a high variability was observed under those treatments. These results contribute to a better understanding of the effect of the sound elements, both individually and in combination, on bacterial systems. © 2018 Society of Chemical Industry
Strong immersion is a well‐quasi‐ordering for semicomplete digraphs
Authors: Barbero Florian , Paul Christophe , Pilipczuk Michał 
Published: October 2018

AbstractWe prove that the strong immersion order is a well‐quasi‐ordering on the class of semicomplete digraphs, thereby strengthening a result of Chudnovsky and Seymour (2011, J. Comb. Theory, Series B, 101, 47–53) that this holds for the class of tournaments.
The effect of traditional slash‐and‐burn agriculture on soil organic matter, nutrient content, and microbiota in tropical ecosystems of Papua New Guinea
Authors: Kukla Jaroslav , Whitfeld Timothy , Cajthaml Tomáš , Baldrian Petr , Veselá‐Šimáčková Hana , Novotný Vojtěch , Frouz Jan 
Published: October 2018

AbstractSlash‐and‐burn agriculture followed by tillage and western style agriculture often lead to loss of soil organic matter and soil degradation. Traditional slash‐and‐burn agriculture affects large areas of land across the tropical zone. However, there are few detailed studies about this practice. To evaluate the effect of traditional slash‐and‐burn agriculture on soil properties (total C, N, P, and C fractions of soil and available P, Ca, Mg, K, NO3, pH, and microbial community biomass and composition), we studied a chronosequence represented by active gardens, abandoned gardens (5–10 years old), secondary forest in abandoned garden sites (20–40 years old), and primary forest with no evidence of cultivation for at least 60 years. No significant differences between individual succession stages were found in total C, N, and P and in C fractions, pH, conductivity, and microbial biomass. In addition, stocks of C, N, and P in the soil did not differ between succession stages. By contrast, the concentration of available P, Ca, Mg, K, and NO3 was highest in active gardens. Litter was absent in active gardens, and the highest amount of litter on the soil surface was found in primary forest. Our results show that traditional slash‐and‐burn agriculture had a strong effect on nutrient availability but no effect on the total CNP stocks and soil C fractions.
Combined photogrammetry and mechanical testing of fired clay brick
Authors: Batinić M. , Galić M. , Trogrlić B. , Divić V. , Racetin I. , Mihanović A. 
Published: October 2018

AbstractA novel experimental tensile apparatus and testing methodology, developed in order to define necessary material parameters for mathematical formulation of a constitutive model of fired clay brick is presented in this paper. In order to account for irregularities in sample geometry, a photogrammetry workflow for digital 3D reconstruction of samples was conducted, and non‐dimensional coefficients accounting for geometric irregularities of test specimen was introduced. Mechanical tests were carried out on a series of fired clay brick specimens, sampled from brick blocks. Statistically analysed experimental data, corrected with the aforementioned coefficients, yielded modulus of elasticity, Poisson's coefficient, and extreme tensile stress/strain relationships that, were used in the proposed numerical constitutive model.
Hot compression deformation behavior and processing map of Mg–Y–Sr–La(Ce)–Zr biodegradable magnesium alloy
Authors: Liu D. , Liu Z. , Li D. , Pang X. 
Published: October 2018

AbstractThe flow behavior of Mg–4.2Y–1.5Sr‐0.6La(Ce)–0.5Zr biodegradable magnesium alloy was investigated using Gleeble‐1500D thermal simulation test machine at deforming temperature of 350 °C–500 °C, strain rates of 0.001 s‐1–1 s‐1 and the final strain of 60 %. The flow stress constitutive relationship and processing map was established. Meanwhile, the experimental results indicated that flow stress of the Mg–Y–Sr–La(Ce)–Zr alloy increase and then decrease with increase of strain, which is due to work hardening caused by dislocation blocking and softening effects caused by dynamic recrystallization respectively. According to the processing maps and dynamic recrystallization of the alloy, the optimum processing parameters of the alloy are determined with a temperature range of 450 °C–500 °C and strain rate range of 0.006 s‐1–0.009 s‐1.
Influence of gradual replacement of aluminum for copper in FeCrCoNiCu alloys
Authors: Xueqian Y. , Guizhong L. , Yufeng B. , Xintao D. , Jingjie G. 
Published: October 2018

AbstractAlxFeCrCoNiCu1‐x alloys with multiprincipal elements (x values in a molar ratio of 0, 0.2, 0.4, 0.6, 0.8, 1) are prepared by arc melting. When part of copper in the alloy began to be substituted by aluminum, although the microstructure is still the face centered cubic structure, the hardness of the alloy has drastically decreased. With the increase of replacing copper with aluminum, the hardness of alloy increases slowly, and when x = 0.8, rich aluminum nanoparticle precipitation and “Widmanstatten side plates” appear in the alloy, and the hardness of the alloy is increasing greatly. Finally, when the copper is completely replaced by aluminum, the alloy becomes body centered cubic structure, and the hardness reaches the maximum. In terms of ductility, x = 0∼0.6, alloys exhibit the good ductility, and no fracture occurs within the compression range, but the yield strength is relatively low. When x = 0.8∼1, the ductility of the alloy decreases obviously, and the cleavage fracture appears in the compression range, but the yield strength is greatly improved. Among these alloys, it can be found that these mechanical changes are closely related to changes in microstructure.
Development of a virtual training environment to enhance live cataract surgical training
Authors: Strauss Glenn H. , Gulasy Dennis , Allard Jeremie 
Published: October 2018

AbstractThe world of virtual reality‐based training is gradually reaching into the field of ophthalmology, but the methodology for creating high‐fidelity simulation tools is largely unexplored and slowly catching up with the curve of available technology. This paper explores many of the challenges involved in the development of new technology in the hopes of encouraging research and development.