bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrophysiological Properties and Viability of Neonatal Rat Ventricular Myocyte Cultures with Inducible ChR2 Expression
Authors: Li Qince , Ni Rong , Hong Huixian , Goh Kah Yong , Rossi Michael , Fast Vladimir G. , Zhou Lufang 
Published: May 2017

AbstractChannelrhodopsin-2 (ChR2)-based optogenetic technique has been increasingly applied to cardiovascular research. However, the potential effects of ChR2 protein overexpression on cardiomyocytes are not completely understood. The present work aimed to examine how the doxycycline-inducible lentiviral-mediated ChR2 expression may affect cell viability and electrophysiological property of neonatal rat ventricular myocyte (NRVM) cultures. Primary NVRMs were infected with lentivirus containing ChR2 or YFP gene and subjected to cytotoxicity analysis. ChR2-expressing cultures were then paced electrically or optically with a blue light-emitting diode, with activation spread recorded simultaneously using optical mapping. Results showed that ChR2 could be readily transduced to NRVMs by the doxycycline-inducible lentiviral system; however, high-level ChR2 (but not YFP) expression was associated with substantial cytotoxicity, which hindered optical pacing. Application of bromodeoxyuridine significantly reduced cell damage, allowing stimulation with light. Simultaneous optical Vm mapping showed that conduction velocity, action potential duration, and dVm/dtmax were similar in ChR2-expressing and control cultures. Finally, the ChR2-expressing cultures could be optically paced at multiple sites, with significantly reduced overall activation time. In summary, we demonstrated that inducible lentiviral-mediated ChR2 overexpression might cause cytotoxicity in NRVM cultures, which could be alleviated without impairing electrophysiological function, allowing simultaneous optical pacing and Vm mapping.
Pattern analysis of laser-tattoo interactions for picosecond- and nanosecond-domain 1,064-nm neodymium-doped yttrium-aluminum-garnet lasers in tissue-mimicking phantom
Authors: Ahn Keun Jae , Zheng Zhenlong , Kwon Tae Rin , Kim Beom Joon , Lee Hye Sun , Cho Sung Bin 
Published: May 2017

AbstractDuring laser treatment for tattoo removal, pigment chromophores absorb laser energy, resulting in fragmentation of the ink particles via selective photothermolysis. The present study aimed to outline macroscopic laser-tattoo interactions in tissue-mimicking (TM) phantoms treated with picosecond- and nanosecond-domain lasers. Additionally, high-speed cinematographs were captured to visualize time-dependent tattoo-tissue interactions, from laser irradiation to the formation of photothermal and photoacoustic injury zones (PIZs). In all experimental settings using the nanosecond or picosecond laser, tattoo pigments fragmented into coarse particles after a single laser pulse, and further disintegrated into smaller particles that dispersed toward the boundaries of PIZs after repetitive delivery of laser energy. Particles fractured by picosecond treatment were more evenly dispersed throughout PIZs than those fractured by nanosecond treatment. Additionally, picosecond-then-picosecond laser treatment (5-pass-picosecond treatment + 5-pass-picosecond treatment) induced greater disintegration of tattoo particles within PIZs than picosecond-then-nanosecond laser treatment (5-pass-picosecond treatment + 5-pass-nanosecond treatment). High-speed cinematography recorded the formation of PIZs after repeated reflection and propagation of acoustic waves over hundreds of microseconds to a few milliseconds. The present data may be of use in predicting three-dimensional laser-tattoo interactions and associated reactions in surrounding tissue.
Regulation of CHK1 by mTOR contributes to the evasion of DNA damage barrier of cancer cells
Authors: Zhou Xinhui , Liu Weijin , Hu Xing , Dorrance Adrienne , Garzon Ramiro , Houghton Peter J. , Shen Changxian 
Published: May 2017

AbstractOncogenic transformation leads to dysregulated cell proliferation, nutrient deficiency, and hypoxia resulting in metabolic stress and increased DNA damage. In normal cells, such metabolic stress leads to inhibition of signaling through the mammalian Target of Rapamycin Complex 1 (mTORC1), reduction of protein translation, cell cycle arrest, and conservation of energy. In contrast, negative regulation of mTORC1 signaling by DNA damage is abrogated in many cancer cells, thus mTORC1 signaling remains active under microenvironmental conditions that potentially promote endogenous DNA damage. Here we report that mTORC1 signaling suppresses endogenous DNA damage and replication stress. Pharmacological inhibition of mTOR signaling resulted in phosphorylation of H2AX concomitant with the decrease of CHK1 levels both in cell culture and mouse rhadomyosarcoma xenografts. Further results demonstrated that mTORC1-S6K1 signaling controls transcription of CHK1 via Rb-E2F by upregulating cyclin D and E. Consistent with these results, downregulation of CHK1 by inhibition of mTOR kinase resulted in defects in the slow S phase progression following DNA damage. These results indicate that, under stressful conditions, maintained mTORC1 signaling in cancer cells promotes survival by suppressing endogenous DNA damage, and may control cell fate through the regulation of CHK1.
A molecular beacon-based approach for live-cell imaging of RNA transcripts with minimal target engineering at the single-molecule level
Authors: Chen Mingming , Ma Zhao , Wu Xiaotian , Mao Shiqi , Yang Yantao , Tan Jie , Krueger Christopher J. , Chen Antony K. 
Published: May 2017

AbstractAnalysis of RNA dynamics and localization at the single-molecule level in living cells has been predominantly achieved by engineering target RNAs with large insertions of tandem repeat sequences that are bound by protein-based or oligonucleotide-based fluorescent probes. Thus, individual RNAs are tagged by multiple fluorescent probes, making them detectable by fluorescence microscopy. Since large insertions may affect RNA processes including trafficking and localization, here we present a strategy to visualize single RNA transcripts in living cells using molecular beacons (MBs) - fluorogenic oligonucleotide probes - with minimal target engineering. The MBs are composed of 2′-O-methyl RNAs with a fully phosphorothioate-modified loop domain (2Me/PSLOOP MBs), an architecture that elicits marginal levels of nonspecific signals in cells. We showed that MBs can detect single transcripts containing as few as 8 target repeat sequences with ~90% accuracy. In both the nucleus and the cytoplasm, mRNAs harboring 8 repeats moved faster than those with 32 repeats, suggesting that intracellular activities are less impeded by smaller engineered insertions. We then report the first MB-based imaging of intracellular dynamics and localization of single long noncoding RNAs (lncRNAs). We envision the proposed minimally-engineered, MB-based technology for live-cell single-molecule RNA imaging could facilitate new discoveries in RNA research.
DNA Methyltransferase1 (DNMT1) Isoform3 methylates mitochondrial genome and modulates its biology
Authors: Saini Sunil Kumar , Mangalhara Kailash Chandra , Prakasam Gopinath , Bamezai R. N. K. 
Published: May 2017

AbstractHere we demonstrate localization of the isoform3 of DNA Methyltransferase1 (DNMT1) enzyme to mitochondria, instead of isoform1 as reported earlier. The fused DNMT1-isoform1, reported earlier to localize in mitochondria, surprisingly showed its exclusive presence inside the nucleus after its ectopic expression; and failed to localize in mitochondria. On the other hand, ectopically expressed DNMT1-isoform3 targeted itself to mitochondria and subsequently methylated CpG regions in the mitochondrial genome. In addition, overexpression of DNMT1-isoform3 affected mitochondrial biology and regulated its function. Under different conditions of oxidative and nutritional stress, this isoform was down-regulated, resulting in hypomethylation of mitochondrial genome. Our study reveals how DNMT1-isoform3, instead of isoform1, is responsible for mtDNA methylation, influencing its biology.
Characterizing microglia activation: a spatial statistics approach to maximize information extraction
Authors: Davis Benjamin M. , Salinas-Navarro Manual , Cordeiro M. Francesca , Moons Lieve , De Groef Lies 
Published: May 2017

AbstractMicroglia play an important role in the pathology of CNS disorders, however, there remains significant uncertainty about the neuroprotective/degenerative role of these cells due to a lack of techniques to adequately assess their complex behaviour in response to injury. Advancing microscopy techniques, transgenic lines and well-characterized molecular markers, have made histological assessment of microglia populations more accessible. However, there is a distinct lack of tools to adequately extract information from these images to fully characterise microglia behaviour. This, combined with growing economic pressures and the ethical need to minimise the use of laboratory animals, led us to develop tools to maximise the amount of information obtained. This study describes a novel approach, combining image analysis with spatial statistical techniques. In addition to monitoring morphological parameters and global changes in microglia density, nearest neighbour distance, and regularity index, we used cluster analyses based on changes in soma size and roundness to yield novel insights into the behaviour of different microglia phenotypes in a murine optic nerve injury model. These methods should be considered a generic tool to quantitatively assess microglia activation, to profile phenotypic changes into microglia subpopulations, and to map spatial distributions in virtually every CNS region and disease state.
Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota
Authors: Zhou Da , Pan Qin , Shen Feng , Cao Hai-xia , Ding Wen-jin , Chen Yuan-wen , Fan Jian-gao 
Published: May 2017

AbstractNon-alcoholic steatohepatitis (NASH) is an epidemic metabolic disease with limited therapeutic strategies. Cumulative data support the pivotal role of gut microbiota in NASH. Here, we investigated the hypothesis regarding whether fecal microbiota transplantation (FMT) is effective in attenuating high-fat diet (HFD)-induced steatohepatitis in mice. Mice were randomized into control, HFD and HFD + FMT groups. After an 8-week HFD, FMT treatment was initiated and carried out for 8 weeks. The gut microbiota structure, butyrate concentrations of the cecal content, liver pathology and intrahepatic lipid and cytokines were examined. Our results showed that after FMT, the gut microbiota disturbance was corrected in HFD-fed mice with elevated abundances of the beneficial bacteria Christensenellaceae and Lactobacillus. FMT also increased butyrate concentrations of the cecal content and the intestinal tight junction protein ZO-1, resulting in relief of endotoxima in HFD-fed mice. Steatohepatitis was alleviated after FMT, as indicated by a significant decrease in intrahepatic lipid accumulation (reduced Oli-red staining, decreased intrahepatic triglyceride and cholesterol), intrahepatic pro-inflammatory cytokines, and the NAS score. Accordingly, intrahepatic IFN-γ and IL-17 were decreased, but Foxp3, IL-4 and IL-22 were increased after FMT intervention. These data indicate that FMT attenuated HFD-induced steatohepatitis in mice via a beneficial effect on the gut microbiota.
Improved thermostability of an acidic xylanase from Aspergillus sulphureus by combined disulphide bridge introduction and proline residue substitution
Authors: Yang Wenhan , Yang Yongzhi , Zhang Lingdi , Xu Hang , Guo Xiaojing , Yang Xu , Dong Bing , Cao Yunhe 
Published: May 2017

AbstractAs a feed additive, xylanase has been widely applied in the feed of monogastric animals, which contains multiple plant polysaccharides. However, during feed manufacture, the high pelleting temperatures challenge wild-type xylanases. The aim of this study was to improve the thermostability of Aspergillus sulphureus acidic xylanase. According to the predicted protein structure, a series of disulphide bridges and proline substitutions were created in the xylanase by PCR, and the mutants were expressed in Pichia pastoris. Enzyme properties were evaluated following chromatographic purification. All the recombinant enzymes showed optima at pH 3.0 and 50 °C or 55 °C and better resistance to some chemicals except for CuSO4. The specific activity of the xylanase was decreased by introduction of the mutations. Compared to the wild-type enzyme, a combined mutant, T53C-T142C/T46P, with a disulphide bond at 53–142 and a proline substitution at 46, showed a 22-fold increase of half-life at 60 °C. In a 10-L fermentor, the maximal xylanase activity of T53C-T142C/T46P reached 1,684 U/mL. It was suggested that the T53C-T142C/T46P mutant xylanase had excellent thermostability characteristics and could be a prospective additive in feed manufacture.
The new competitive mechanism of hydrogen bonding interactions and transition process for the hydroxyphenyl imidazo [1, 2-a] pyridine in mixed liquid solution
Authors: Li Yongqing , Yang Yunfan , Ding Yong 
Published: May 2017

AbstractThe new competitive mechanism of intermolecular and intramolecular hydrogen bond can be proposed with an improved mixed model. Upon the photoinduced process, the twisting intramolecular charge transfer (TICT) structure of the hydroxyphenyl imidazo [1, 2-a] pyridine (HPIP) can be obtained. TICT character prompts the fluorescent inactivation via non-radiative decay process. For exploring the photochemical and photophysical properties, the electronic spectra and the infrared (IR) vibrational spectra of titled compounds have been detailedly investigated. In addition, the frontier molecular orbitals (MOs) analysis visually reveals that the unbalanced electron population can give rise to the torsion of molecular structure. To further give an attractive insight into the non-radiative decay process, the potential energy curves have been depicted on the ground state (S0), the first excited state (S1) and the triple excited state (T1). Minimum energy crossing point (MECP) has been found in the S1 and T1 state. On the MECP, the intersystem crossing (ISC) might be dominant channel. The density functional theory (DFT) and the time-dependent density functional theory (TDDFT) methods have been throughout employed in the S0 state, T1 state and S1 state, respectively. The theoretical results are consistent with experiment in mixed and PCM model.
Measuring nanoscale viscoelastic parameters of cells directly from AFM force-displacement curves
Authors: Efremov Yuri M. , Wang Wen-Horng , Hardy Shana D. , Geahlen Robert L. , Raman Arvind 
Published: May 2017

AbstractForce-displacement (F-Z) curves are the most commonly used Atomic Force Microscopy (AFM) mode to measure the local, nanoscale elastic properties of soft materials like living cells. Yet a theoretical framework has been lacking that allows the post-processing of F-Z data to extract their viscoelastic constitutive parameters. Here, we propose a new method to extract nanoscale viscoelastic properties of soft samples like living cells and hydrogels directly from conventional AFM F-Z experiments, thereby creating a common platform for the analysis of cell elastic and viscoelastic properties with arbitrary linear constitutive relations. The method based on the elastic-viscoelastic correspondence principle was validated using finite element (FE) simulations and by comparison with the existed AFM techniques on living cells and hydrogels. The method also allows a discrimination of which viscoelastic relaxation model, for example, standard linear solid (SLS) or power-law rheology (PLR), best suits the experimental data. The method was used to extract the viscoelastic properties of benign and cancerous cell lines (NIH 3T3 fibroblasts, NMuMG epithelial, MDA-MB-231 and MCF-7 breast cancer cells). Finally, we studied the changes in viscoelastic properties related to tumorigenesis including TGF-β induced epithelial-to-mesenchymal transition on NMuMG cells and Syk expression induced phenotype changes in MDA-MB-231 cells.
Risk factors for Pneumocystis jirovecii pneumonia (PJP) in kidney transplantation recipients
Authors: Lee Su Hwan , Huh Kyu Ha , Joo Dong Jin , Kim Myoung Soo , Kim Soon Il , Lee Juhan , Park Moo Suk , Kim Young Sam , Kim Se Kyu , Chang Joon , Kim Yu Seun , Kim Song Yee 
Published: May 2017

AbstractPneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that occurs in immunocompromised patients. The aim of this study was to evaluate risk factors for PJP in kidney transplantation recipients. We conducted a retrospective analysis of patient data from 500 consecutive kidney transplants performed at Severance Hospital between April 2011 and April 2014. Eighteen kidney transplantation recipients (3.6%) were diagnosed with PJP. In the univariate analysis, acute graft rejection, CMV infection, use of medication for diabetes mellitus, and lowest lymphocyte count were associated with PJP. Recipients who experienced acute graft rejection (odds ratio [OR] 11.81, 95% confidence interval [CI] 3.06–45.57, P < 0.001) or developed CMV infection (OR 5.42, 95% CI 1.69–17.39, P = 0.005) had high odds of PJP in multivariate analysis. In the acute graft rejection subgroup, patients treated with anti-thymocyte globulin (ATG) had significantly higher odds of PJP (OR 5.25, 95% CI 1.01–27.36, P = 0.006) than those who were not. Our data suggest that acute graft rejection and CMV infection may be risk factors for PJP in kidney transplant patients. The use of ATG for acute graft rejection may increase the risk of PJP.
Tyrosine kinase inhibitors of Ripk2 attenuate bacterial cell wall-mediated lipolysis, inflammation and dysglycemia
Authors: Duggan Brittany M. , Foley Kevin P. , Henriksbo Brandyn D. , Cavallari Joseph F. , Tamrakar Akhilesh K. , Schertzer Jonathan D. 
Published: May 2017

AbstractInflammation underpins aspects of insulin resistance and dysglycemia. Microbiota-derived cell wall components such as muropeptides or endotoxin can trigger changes in host immunity and metabolism. Specific peptidoglycan motifs promote metabolic tissue inflammation, lipolysis and insulin resistance via Nucleotide-binding oligomerization domain-containing protein 1 (Nod1). Receptor-interacting serine/threonine-protein kinase 2 (Ripk2) mediates Nod1-induced immunity, but the role of Ripk2 in metabolism is ill-defined. We hypothesized that Ripk2 was required for Nod1-mediated inflammation, lipolysis and dysglycemia. This is relevant because certain tyrosine kinase inhibitors (TKIs) inhibit Ripk2 and there is clinical evidence of TKIs lowering inflammation and blood glucose. Here, we showed that only a subset of TKIs known to inhibit Ripk2 attenuated Nod1 ligand-mediated adipocyte lipolysis. TKIs that inhibit Ripk2 decreased cytokine responses induced by Nod1-activating peptidoglycan, but not endotoxin in both metabolic and immune cells. Pre-treatment of adipocytes or macrophages with the TKI gefitinib inhibited Nod1-induced Cxcl1 and Il-6 secretion. Furthermore, treatment of mice with gefitinib prevented Nod1-induced glucose intolerance in vivo. Ripk2 was required for these effects on inflammation and metabolism, since Nod1-mediated cytokine and blood glucose changes were absent in Ripk2−/− mice. Our data show that specific TKIs used in cancer also inhibit Nod1-Ripk2 immunometabolism responses indicative of metabolic disease.
Extent of Visceral Pleural Invasion Affects Prognosis of Resected Non-small Cell Lung Cancer: A meta-analysis
Authors: Wang Ting , Zhou Chengya , Zhou Qinghua 
Published: May 2017

AbstractVisceral pleural invasion (VPI) has been known to be an adverse prognostic factor in non-small cell lung cancer (NSCLC). However, the prognostic significance of extent of VPI (PL0, PL1 and PL2) remains controversial. We conduct a meta-analysis to summarize available evidence on this topic. PubMed, EMBASE, OVID and The Cochrane Library were searched for published studies from inception to May 9, 2016. A total of 16 studies were included in meta-analysis. Our results showed that patients with PL1 or PL2 had poorer overall survival compared with PL0 (HR = 1.555, 95% CI 1.399, 1.730; HR = 2.447, 95% CI 1.913, 3.130) and patients with PL2 had even poorer overall survival than PL1 (HR = 1.287, 95% CI 1.114, 1.487). Patients with PL1 or PL2 had lower 5-year survival rate than PL0 patients (OR = 0.515, 95% CI 0.415, 0.640; OR = 0.441, 95% CI 0.336, 0.579) and patients with PL2 had even lower 5-year survival rate than PL1 (OR = 0.706, 95% CI 0.545, 0.915). In conclusion, extent of VPI impacts the prognosis of resected NSCLC and VPI should be categorized as PL1 and PL2 in the terms of clinical practice and trials.
Enhanced stability of filament-type resistive switching by interface engineering
Authors: Zhu Y. B. , Zheng K. , Wu X. , Ang L. K. 
Published: May 2017

AbstractThe uncontrollable rupture of the filament accompanied with joule heating deteriorates the resistive switching devices performance, especially on endurance and uniformity. To suppress the undesirable filaments rupture, this work presents an interface engineering methodology by inducing a thin layer of NiOx into a sandwiched Al/TaOx/ITO resistive switching device. The NiOx/TaOx interface barrier can confine the formation and rupture of filaments throughout the entire bulk structure under critical bias setups. The physical mechanism behind is the space-charge-limited conduction dominates in the SET process, while the Schottky emission dominates under the reverse bias.
Effect of alkaline preswelling on the structure of lignins from Eucalyptus
Authors: Chen Wei-Jing , Yang Sheng , Zhang Yun , Wang Yun-Yan , Yuan Tong-Qi , Sun Run-Cang 
Published: May 2017

AbstractA clear elucidation of structural feature of whole lignin in plant cell wall is of great importance for understanding lignin biosynthesis mechanism and developing lignin based chemicals or materials under the current biorefinery scenario. Swollen residual enzyme lignin (SREL) has been identified as an ideal representative for native lignin in the plant walls. To investigate the influence of preswelling conditions on the structural features, the SREL obtained through preswelling the ball-milled Eucalyptus wood powder in 2, 4 and 8% NaOH solutions and subsequent in-situ enzymatic hydrolysis were thoroughly characterized. A cellulolytic enzyme lignin (CEL) was also prepared as a comparison. The quantitative NMR analyses indicated that the relative contents of β-O-4′ linkages in SRELs were higher than that in CEL. The lignin structure tended to undergo more destruction with the elevated NaOH concentration. A relatively low NaOH concentration (2% in this study), which could be applied to effectively remove hemicelluloses and transform cellulose structure from cellulose I to cellulose II, was competent to prepare SREL as an ideal representative for the protolignin. An optimization of SREL preparation was essential for a better understanding of the whole protolignin.