bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2
Authors: Zhang Haikuo , Fillmore Brainson Christine , Koyama Shohei , Redig Amanda J. , Chen Ting , Li Shuai , Gupta Manav , Garcia-de-Alba Carolina , Paschini Margherita , Herter-Sprie Grit S. , Lu Gang , Zhang Xin , Marsh Bryan P. , Tuminello Stephanie J. , Xu Chunxiao , Chen Zhao , Wang Xiaoen , Akbay Esra A. , Zheng Mei , Palakurthi Sangeetha , Sholl Lynette M. , Rustgi Anil K. , Kwiatkowski David J. , Diehl J Alan , Bass Adam J. , Sharpless Norman E. , Dranoff Glenn , Hammerman Peter S. , Ji Hongbin , Bardeesy Nabeel , Saur Dieter , Watanabe Hideo , Kim Carla F. , Wong Kwok-Kin 
Published: April 2017

AbstractAdenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions. The pattern of high EZH2, but low H3K27me3 mark, is also prevalent in human lung SCC and SCC regions within ADSCC tumours. Using FACS-isolated populations, we demonstrate that bronchioalveolar stem cells and club cells are the likely cells-of-origin for SCC transitioned tumours. These findings shed light on the epigenetics and cellular origins of lineage-specific lung tumours.
SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis
Authors: Rocca Daniel L. , Wilkinson Kevin A. , Henley Jeremy M. 
Published: April 2017

AbstractForkhead Box P (FOXP) transcriptional repressors play a major role in brain development and their dysfunction leads to human cognitive disorders. However, little is known about how the activity of these proteins is regulated. Here, we show that FOXP1 SUMOylation at lysine 670 is required for recruiting the co-repressor CtBP1 and transcriptional repression. FOXP1 SUMOylation is tightly controlled by neuronal activity, in which synapse to nucleus signalling, mediated via NMDAR and L-type calcium channels, results in rapid FOXP1 deSUMOylation. Knockdown of FOXP1 in cultured cortical neurons stunts dendritic outgrowth and this phenotype cannot be rescued by replacement with a non-SUMOylatable FOXP1-K670R mutant, indicating that SUMOylation of FOXP1 is essential for regulation of proper neuronal morphogenesis. These results suggest that activity-dependent SUMOylation of FOXP1 may be an important mediator of early cortical development and neuronal network formation in the brain.
Light Induced Electron-Phonon Scattering Mediated Resistive Switching in Nanostructured Nb Thin Film Superconductor
Authors: Kazim Shafaq , Sharma Alka , Yadav Sachin , Gajar Bikash , Joshi Lalit M. , Mishra Monu , Gupta Govind , Husale Sudhir , Gupta Anurag , Sahoo Sangeeta , Ojha V. N. 
Published: April 2017

abstractThe elemental Nb is mainly investigated for its eminent superconducting properties. In contrary, we report of a relatively unexplored property, namely, its superior optoelectronic property in reduced dimension. We demonstrate here that nanostructured Nb thin films (NNFs), under optical illumination, behave as room temperature photo-switches and exhibit bolometric features below its superconducting critical temperature. Both photo-switch and superconducting bolometric behavior are monitored by its resistance change with light in visible and near infrared (NIR) wavelength range. Unlike the conventional photodetectors, the NNF devices switch to higher resistive states with light and the corresponding resistivity change is studied with thickness and grain size variations. At low temperature in its superconducting state, the light exposure shifts the superconducting transition towards lower temperature. The room temperature photon sensing nature of the NNF is explained by the photon assisted electron-phonon scattering mechanism while the low temperature light response is mainly related to the heat generation which essentially changes the effective temperature for the device and the device is capable of sensing a temperature difference of few tens of milli-kelvins. The observed photo-response on the transport properties of NNFs can be very important for future superconducting photon detectors, bolometers and phase slip based device applications.
Room-temperature field effect transistors with metallic ultrathin TiN-based channel prepared by atomic layer delta doping and deposition
Authors: Cheng Po-Hsien , Wang Chun-Yuan , Chang Teng-Jan , Shen Tsung-Han , Cai Yu-Syuan , Chen Miin-Jang 
Published: April 2017

AbstractMetallic channel transistors have been proposed as the candidate for sub-10 nm technology node. However, the conductivity modulation in metallic channels can only be observed at low temperatures usually below 100 K. In this study, room-temperature field effect and modulation of the channel resistance was achieved in the metallic channel transistors, in which the oxygen-doped TiN ultrathin-body channels were prepared by the atomic layer delta doping and deposition (AL3D) with precise control of the channel thickness and electron concentration. The decrease of channel thickness leads to the reduction in electron concentration and the blue shift of absorption spectrum, which can be explained by the onset of quantum confinement effect. The increase of oxygen incorporation results in the increase of interband gap energy, also giving rise to the decrease in electron concentration and the blue shift of absorption spectrum. Because of the significant decrease in electron concentration, the screening effect was greatly suppressed in the metallic channel. Therefore, the channel modulation by the gate electric field was achieved at room temperature due to the quantum confinement and suppressed screening effect with the thickness down to 4.8 nm and the oxygen content up to 35% in the oxygen-doped TiN ultrathin-body channel.
Monitoring of dynamic changes in Keyhole Limpet Hemocyanin (KLH)-specific B cells in KLH-vaccinated cancer patients
Authors: Wimmers Florian , de Haas Nienke , Scholzen Anja , Schreibelt Gerty , Simonetti Elles , Eleveld Marc J. , Brouwers Huberdina M. L. M. , Beldhuis-Valkis Marjo , Joosten Irma , de Jonge Marien I. , Gerritsen Winald R. , de Vries I. Jolanda M. , Diavatopoulos Dimitri A. , Jacobs Joannes F. M. 
Published: April 2017

AbstractKeyhole limpet hemocyanin (KLH) is used as an immunogenic neo-antigen for various clinical applications and during vaccine development. For advanced monitoring of KLH-based interventions, we developed a flow cytometry-based assay for the ex vivo detection, phenotyping and isolation of KLH-specific B cells. As proof-of-principle, we analyzed 10 melanoma patients exposed to KLH during anti-cancer dendritic cell vaccination. Our assay demonstrated sensitive and specific detection of KLH-specific B cells in peripheral blood and KLH-specific B cell frequencies strongly correlated with anti-KLH serum antibody titers. Profiling of B cell subsets over the vaccination course revealed that KLH-specific B cells matured from naïve to class-switched memory B cells, confirming the prototypic B cell response to a neo-antigen. We conclude that flow-cytometric detection and in-depth phenotyping of KLH-specific B cells is specific, sensitive, and scalable. Our findings provide novel opportunities to monitor KLH-specific immune responses and serve as a blueprint for the development of new flow-cytometric protocols.
Hypertension and the risk of endometrial cancer: a systematic review and meta-analysis of case-control and cohort studies
Authors: Aune Dagfinn , Sen Abhijit , Vatten Lars J. 
Published: April 2017

AbstractA history of hypertension has been associated with increased risk of endometrial cancer in several studies, but the results have not been consistent. We conducted a systematic review and meta-analysis of case-control and cohort studies to clarify the association between hypertension and endometrial cancer risk. PubMed and Embase databases were searched up to 27th of February 2016. Prospective and case-control studies which reported adjusted relative risk estimates and 95% confidence intervals of endometrial cancer associated with a hypertension diagnosis were included. Summary relative risks were estimated using a random effects model. Nineteen case-control studies and 6 cohort studies were included. The summary RR was 1.61 (95% CI: 1.41–1.85, I2 = 86%) for all studies, 1.73 (95% CI: 1.45–2.06, I2 = 89%) for case-control studies and 1.32 (95% CI: 1.12–1.56, I2 = 47%) for cohort studies. The association between hypertension and endometrial cancer was weaker, but still significant, among studies with adjustment for smoking, BMI, oral contraceptive use, and parity, compared to studies without such adjustment. This meta-analysis suggest an increased risk of endometrial cancer among patients with hypertension, however, further studies with more comprehensive adjustments for confounders are warranted to clarify the association.
Computational fluid dynamics simulation of the upper airway response to large incisor retraction in adult class I bimaxillary protrusion patients
Authors: Zheng Zhe , Liu Hong , Xu Qi , Wu Wei , Du Liling , Chen Hong , Zhang Yiwen , Liu Dongxu 
Published: April 2017

AbstractThe changes of the upper airway after large retraction of the incisors in adult class I bimaxillary protrusion patients were assessed mainly focused on the anatomic variation and ignored the functional changes. This study aimed to investigate the changes of the upper airway in adult class I bimaxillary protrusion patients after extraction treatment using the functional images based on computational fluid dynamics (CFD). CFD was implemented after 3D reconstruction based on the CBCT of 30 patients who have completed extraction treatment. After treatment, pressure drop in the minimum area, oropharynx, and hypopharynx increased significantly. The minimum pressure and the maximum velocity mainly located in the hypopharynx in pre-treatment while they mostly occured in the oropharynx after treatment. Statistically significant correlation between pressure drop and anatomic parameters, pressure drop and treatment outcomes was found. No statistical significance changes in pressure drop and volume of nasopharynx was found. This study suggested that the risk of pharyngeal collapsing become higher after extraction treatment with maximum anchorage in bimaxillary protrusion adult patients. Those adverse changes should be taken into consideration especially for high-risk patients to avoid undesired weakening of the respiratory function in clinical treatment.
pH-Controlled Cerium Oxide Nanoparticle Inhibition of Both Gram-Positive and Gram-Negative Bacteria Growth
Authors: Alpaslan Ece , Geilich Benjamin M. , Yazici Hilal , Webster Thomas J. 
Published: April 2017

AbstractHere, the antibacterial activity of dextran-coated nanoceria was examined against Pseudomonas aeruginosa and Staphylococcus epidermidis by varying the dose, the time of treatment, and the pH of the solution. Findings suggested that dextran-coated nanoceria particles were much more effective at killing P. aeruginosa and S. epidermidis at basic pH values (pH = 9) compared to acidic pH values (pH = 6) due to a smaller size and positive surface charge at pH 9. At pH 9, different particle concentrations did cause a delay in the growth of P. aeruginosa, whereas impressively S. epidermidis did not grow at all when treated with a 500 μg/mL nanoceria concentration for 24 hours. For both bacteria, a 2 log reduction and elevated amounts of reactive oxygen species (ROS) generation per colony were observed after 6 hours of treatment with nanoceria at pH 9 compared to untreated controls. After 6 hours of incubation with nanoceria at pH 9, P. aeruginosa showed drastic morphological changes as a result of cellular stress. In summary, this study provides significant evidence for the use of nanoceria (+4) for a wide range of anti-infection applications without resorting to the use of antibiotics, for which bacteria are developing a resistance towards anyway.
High Temperature Deformation Mechanism in Hierarchical and Single Precipitate Strengthened Ferritic Alloys by In Situ Neutron Diffraction Studies
Authors: Song Gian , Sun Zhiqian , Li Lin , Clausen Bjørn , Zhang Shu Yan , Gao Yanfei , Liaw Peter K. 
Published: April 2017

AbstractThe ferritic Fe-Cr-Ni-Al-Ti alloys strengthened by hierarchical-Ni2TiAl/NiAl or single-Ni2TiAl precipitates have been developed and received great attentions due to their superior creep resistance, as compared to conventional ferritic steels. Although the significant improvement of the creep resistance is achieved in the hierarchical-precipitate-strengthened ferritic alloy, the in-depth understanding of its high-temperature deformation mechanisms is essential to further optimize the microstructure and mechanical properties, and advance the development of the creep resistant materials. In the present study, in-situ neutron diffraction has been used to investigate the evolution of elastic strain of constitutive phases and their interactions, such as load-transfer/load-relaxation behavior between the precipitate and matrix, during tensile deformation and stress relaxation at 973 K, which provide the key features in understanding the governing deformation mechanisms. Crystal-plasticity finite-element simulations were employed to qualitatively compare the experimental evolution of the elastic strain during tensile deformation at 973 K. It was found that the coherent elastic strain field in the matrix, created by the lattice misfit between the matrix and precipitate phases for the hierarchical-precipitate-strengthened ferritic alloy, is effective in reducing the diffusional relaxation along the interface between the precipitate and matrix phases, which leads to the strong load-transfer capability from the matrix to precipitate.
In-vivo Comparison of 18F-FLT uptake, CT Number, Tumor Volume in Evaluation of Repopulation during Radiotherapy for Lung cancer
Authors: Zhang Xiaoli , Yu Jinming , Li Chengming , Sun Xindong , Meng Xue 
Published: April 2017

AbstractAccelerated repopulation has been observed in various tumors. This study was aimed to evaluate the potential of 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) uptake and Computed Tomography Number (CTN) in monitoring tumor responses to radiotherapy compared with tumor volume (TV) changes. Tumor bearing nude mice were assigned to either irradiated daily or every second day group and then randomized to 6 sub-groups to receive 0Gy, 6Gy, 12Gy, 18Gy, 24Gy, 36Gy irradiation, respectively. TV was measured every 3 days. 18F-FLT micro-PET/CT scans were performed after irradiation being completed. Tumor sections were stained to calculate the immunohistochemical (Ki-67) labeling index (LI). Comparison analysis between FLT uptake parameters, CTNs, VTs and Ki-67 LI results were conducted to determine the correlation. Ki-67 LI increased significantly after 6 times of irradiation at irradiated daily group and after 3 times at irradiated every second day group, suggesting accelerated repopulation. No shrinkage of TV was noticed at two groups during irradiation delivery. Both 18F-FLT uptake and CTN increased significantly after irradiation of 12Gy/6f/6d and 6Gy/3f/6d. Comparison analysis found a significant relationship between Ki-67 LI and 18F-FLT uptake parameters as well as CTN. Both 18F-FLT PET and CT have the potential to reflect the tumor proliferative response during radiation delivery.
Characterization of the influence of chlororespiration on the regulation of photosynthesis in the glaucophyte Cyanophora paradoxa
Authors: Misumi Masahiro , Sonoike Kintake 
Published: April 2017

AbstractGlaucophytes are primary symbiotic algae with unique plastids called cyanelles, whose structure is most similar to ancestral cyanobacteria among plastids in photosynthetic organisms. Here we compare the regulation of photosynthesis in glaucophyte with that in cyanobacteria in the aim of elucidating the changes caused by the symbiosis in the interaction between photosynthetic electron transfer and other metabolic pathways. Chlorophyll fluorescence measurements of the glaucophyte Cyanophora paradoxa NIES-547 indicated that plastoquinone (PQ) pool in photosynthetic electron transfer was reduced in the dark by chlororespiration. The levels of nonphotochemical quenching of chlorophyll fluorescence was high in the dark but decreased under low light, and increased again under high light. This type of concave light dependence was quite similar to that observed in cyanobacteria. Moreover, the addition of ionophore hardly affected nonphotochemical quenching, suggesting state transition as a main component of the regulatory system in C. paradoxa. These results suggest that cyanelles of C. paradoxa retain many of the characteristics observed in their ancestral cyanobacteria. From the viewpoint of metabolic interactions, C. paradoxa is the primary symbiotic algae most similar to cyanobacteria than other lineages of photosynthetic organisms.
Novel miRNA-mRNA interactions conserved in essential cancer pathways
Authors: Andrés-León Eduardo , Cases Ildefonso , Alonso Sergio , Rojas Ana M. 
Published: April 2017

AbstractCancer is a complex disease in which unrestrained cell proliferation results in tumour development. Extensive research into the molecular mechanisms underlying tumorigenesis has led to the characterization of oncogenes and tumour suppressors that are key elements in cancer growth and progression, as well as that of other important elements like microRNAs. These genes and miRNAs appear to be constitutively deregulated in cancer. To identify signatures of miRNA-mRNA interactions potentially conserved in essential cancer pathways, we have conducted an integrative analysis of transcriptomic data, also taking into account methylation and copy number alterations. We analysed 18,605 raw transcriptome samples from The Cancer Genome Atlas covering 15 of the most common types of human tumours. From this global transcriptome study, we recovered known cancer-associated miRNA-targets and importantly, we identified new potential targets from miRNA families, also analysing the phenotypic outcomes of these genes/mRNAs in terms of survival. Further analyses could lead to novel approaches in cancer therapy.
On the role of residue phosphorylation in 14-3-3 partners: AANAT as a case study
Authors: Masone Diego , Uhart Marina , Bustos Diego M. 
Published: April 2017

AbstractTwenty years ago, a novel concept in protein structural biology was discovered: the intrinsically disordered regions (IDRs). These regions remain largely unstructured under native conditions and the more are studied, more properties are attributed to them. Possibly, one of the most important is their ability to conform a new type of protein-protein interaction. Besides the classical domain-to-domain interactions, IDRs follow a ‘fly-casting’ model including ‘induced folding’. Unfortunately, it is only possible to experimentally explore initial and final states. However, the complete movie of conformational changes of protein regions and their characterization can be addressed by in silico experiments. Here, we simulate the binding of two proteins to describe how the phosphorylation of a single residue modulates the entire process. 14-3-3 protein family is considered a master regulator of phosphorylated proteins and from a modern point-of-view, protein phosphorylation is a three component system, with writers (kinases), erasers (phosphatases) and readers. This later biological role is attributed to the 14-3-3 protein family. Our molecular dynamics results show that phosphorylation of the key residue Thr31 in a partner of 14-3-3, the aralkylamine N-acetyltransferase, releases the fly-casting mechanism during binding. On the other hand, the non-phosphorylation of the same residue traps the proteins, systematically and repeatedly driving the simulations into wrong protein-protein conformations.
Linoleic acid isomerase gene FgLAI12 affects sensitivity to salicylic acid, mycelial growth and virulence of Fusarium graminearum
Authors: Zhang Ya-Zhou , Wei Zhen-Zhen , Liu Cai-Hong , Chen Qing , Xu Bin-Jie , Guo Zhen-Ru , Cao Yong-Li , Wang Yan , Han Ya-Nan , Chen Chen , Feng Xiang , Qiao Yuan-Yuan , Zong Lu-Juan , Zheng Ting , Deng Mei , Jiang Qian-Tao , Li Wei , Zheng You-Liang , Wei Yu-Ming , Qi Peng-Fei 
Published: April 2017

AbstractFusarium graminearum is the major causal agent of fusarium head blight in wheat, a serious disease worldwide. Linoleic acid isomerase (LAI) catalyses the transformation of linoleic acid (LA) to conjugated linoleic acid (CLA), which is beneficial for human health. We characterised a cis-12 LAI gene of F. graminearum (FGSG_02668; FgLAI12), which was downregulated by salicylic acid (SA), a plant defence hormone. Disruption of FgLAI12 in F. graminearum resulted in decreased accumulation of cis-9,trans-11 CLA, enhanced sensitivity to SA, and increased accumulation of LA and SA in wheat spikes during infection. In addition, mycelial growth, accumulation of deoxynivalenol, and pathogenicity in wheat spikes were reduced. Re-introduction of a functional FgLAI12 gene into ΔFgLAI12 recovered the wild-type phenotype. Fluorescent microscopic analysis showed that FgLAI12 protein was usually expressed in the septa zone of conidia and the vacuole of hyphae, but was expressed in the cell membrane of hyphae in response to exogenous LA, which may be an element of LA metabolism during infection by F. graminearum. The cis-12 LAI enzyme encoded by FgLAI12 is critical for fungal response to SA, mycelial growth and virulence in wheat. The gene FgLAI12 is potentially valuable for biotechnological synthesis of cis-9,trans-11 CLA.
Lanatoside C, a cardiac glycoside, acts through protein kinase Cδ to cause apoptosis of human hepatocellular carcinoma cells
Authors: Chao Min-Wu , Chen Tzu-Hsuan , Huang Han-Li , Chang Yu-Wei , HuangFu Wei-Chun , Lee Yu-Ching , Teng Che-Ming , Pan Shiow-Lin 
Published: April 2017

AbstractRecent studies have revealed that cardiac glycosides, such as digitalis and digoxin, have anticancer activity and may serve as lead compounds for the development of cancer treatments. The poor prognosis of hepatocellular carcinoma (HCC) patients reflects the development of resistance to current chemotherapeutic agents, highlighting the need for discovering new small-molecule therapeutics. Here, we found that lanatoside C, an anti-arrhythmic agent extracted from Digitalis lanata, inhibited the growth of HCC cells and dramatically decreased tumor volume as well as delayed tumor growth without obvious body weight loss. Moreover, lanatoside C triggered mitochondrial membrane potential (MMP) loss, activation of caspases and translocation of apoptosis-inducing factor (AIF) into the nucleus, which suggests that lanatoside C induced apoptosis through both caspase-dependent and -independent pathways. Furthermore, we discovered that lanatoside C activated protein kinase delta (PKCδ) via Thr505 phosphorylation and subsequent membrane translocation. Inhibition of PKCδ reversed lanatoside C-induced MMP loss and apoptosis, confirming that lanatoside C caused apoptosis through PKCδ activation. We also found that the AKT/mTOR pathway was negatively regulated by lanatoside C through PKCδ activation. In conclusion, we provide the first demonstration that the anticancer effects of lanatoside C are mainly attributable to PKCδ activation.