bluuebunny/crossref_metadata_2025_split huggingface dataset:
AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-κB and STAT3 Pathways
Authors: Qiu Yiguo , Tao Lifei , Zheng Shijie , Lin Ru , Fu Xinyu , Chen Zihe , Lei Chunyan , Wang Jiaming , Li Hongwei , Li Qiuhong , Lei Bo 
Published: August 2016

AbstractRenin angiotensin system (RAS) is a key hormonal system which regulates the cardiovascular function and is implicated in several autoimmune diseases. With the discovery of the angiotensin-converting enzyme 2 (ACE2), a protective axis of RAS namely ACE2/Ang-(1–7)/Mas that counteracts the deleterious ACE/AngII/AT1R axis has been established. This axis is emerging as a novel target to attenuate ocular inflammation. However, the underlying molecular mechanisms remain unclear. We investigated the hypothesis that enhancing the activity of the protective axis of RAS by subretinal delivery of an AAV8 (Y733F)-ACE2 vector would protect against the ocular inflammation in experimental autoimmune uveitis (EAU) mice through regulating the local immune responses. Our studies demonstrated that increased ACE2 expression exerts protective effects on inflammation in EAU mouse by modulating ocular immune responses, including the differentiation of Th1/Th17 cells and the polarization of M1/M2 macrophages; whereas the systemic immune responses appeared not affected. These effects were mediated by activating the Ang-(1–7)/Mas and inhibiting the MAPK, NF-κB and STAT3 signaling pathways. This proof-of-concept study suggests that activation of ocular ACE2/Ang-(1–7)/Mas axis with AAV gene transfer modulates local immune responses and may be a promising, long-lasting therapeutic strategy for refractory and recurrent uveitis, as well as other inflammatory eye diseases.
A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition
Authors: Gill Martin R. , Harun Siti Norain , Halder Swagata , Boghozian Ramon A. , Ramadan Kristijan , Ahmad Haslina , Vallis Katherine A. 
Published: August 2016

AbstractRuthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)2(PIP)]2+ (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by G1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H2AX (γ-H2AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)2(PIP)]2+ before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H2AX expression, indicating the compound functions as a radiosensitizer. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing.
Higher FT4 or TSH below the normal range are associated with increased risk of dementia: a meta-analysis of 11 studies
Authors: Wu Yue , Pei Yuqing , Wang Fei , Xu Danfei , Cui Wei 
Published: August 2016

AbstractObservational studies of thyroid function and dementia have reported conflicting results. We reviewed cohort and case-control studies from MEDLINE, EMBASE, Web of Science and the Cochrane Library that focused on the association between serum thyroxine, thyrotropin and dementia. A total of 24,952 participants from three case-control and eight cohort studies were included. The relationships between dementia and the per standard deviation (SD) increment of free thyroxine (FT4) (random relative ratio (RR) = 1.08, 95% confidence interval (CI) 1.00–1.17) and thyroid-stimulating hormone (TSH) (fixed RR = 0.91, 95% CI 0.84–0.99) were well established. TSH levels in the low category were associated with an increased risk of dementia (fixed RR = 1.60, 95% CI 1.27–2.00). However, the positive association was confined to TSH levels below the normal range (fixed RR = 1.77, 95% CI 1.31–2.39), not those in the lower tertile of the normal range (fixed RR = 1.39, 95% CI 0.98–1.97). Additionally, dementia was not significantly associated with high TSH levels (fixed RR = 0.99, 95% CI 0.76–1.29). Furthermore, there was no positive association between dementia and the low or high categories of TSH in men. Thus, individuals with higher FT4 levels or those with TSH levels below the normal range have an increased risk of dementia.
A fast multispectral light synthesiser based on LEDs and a diffraction grating
Authors: Belušič Gregor , Ilić Marko , Meglič Andrej , Pirih Primož 
Published: August 2016

AbstractOptical experiments often require fast-switching light sources with adjustable bandwidths and intensities. We constructed a wavelength combiner based on a reflective planar diffraction grating and light emitting diodes with emission peaks from 350 to 630 nm that were positioned at the angles corresponding to the first diffraction order of the reversed beam. The combined output beam was launched into a fibre. The spacing between 22 equally wide spectral bands was about 15 nm. The time resolution of the pulse-width modulation drivers was 1 ms. The source was validated with a fast intracellular measurement of the spectral sensitivity of blowfly photoreceptors. In hyperspectral imaging of Xenopus skin circulation, the wavelength resolution was adequate to resolve haemoglobin absorption spectra. The device contains no moving parts, has low stray light and is intrinsically capable of multi-band output. Possible applications include visual physiology, biomedical optics, microscopy and spectroscopy.
The efficacy and safety of immunotherapy in patients with advanced NSCLC: a systematic review and meta-analysis
Authors: Zhou Liang , Wang Xi-Ling , Deng Qing-Long , Du Yan-Qiu , Zhao Nai-Qing 
Published: August 2016

AbstractImmunotherapy is a novel treatment for advanced non-small cell lung cancer (NSCLC) patients. Immunotherapy includes two main broad classes of therapeutic vaccines and immune checkpoint inhibitors, as well as cytokines, biological response modifiers and cellular therapy. The present systematic review and meta-analysis aims to evaluate the efficacy and safety of different classes of immunotherapy in patients with advanced NSCLC. Literature search was done on Medline, Embase and Cochrane Library. The primary endpoints were overall survival (OS) and grade ≥3 adverse events. Twenty randomized controlled trials were finally identified in our study. Efficacy analysis indicated an improvement of OS in advanced NSCLC patients after treating by therapeutic vaccines and immune checkpoint inhibitors, but not for other immunomodulators. Safety analysis showed that immunotherapy was well-tolerated. All kinds of grade ≥3 adverse events were similar between experimental group and control group except that neutropenia and thrombocytopenia had a higher incidence in patients received vaccines. In conclusion, immunotherapy is a promising treatment for advanced NSCLC patients. Our findings will be further confirmed and supplemented by several phase II and phase III RCTs which are going to complete in near future.
Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients
Authors: Liu Ning Qing , De Marchi Tommaso , Timmermans Annemieke , Trapman-Jansen Anita M. A. C. , Foekens Renée , Look Maxime P. , Smid Marcel , van Deurzen Carolien H. M. , Span Paul N. , Sweep Fred C. G. J. , Brask Julie Benedicte , Timmermans-Wielenga Vera , Foekens John A. , Martens John W. M. , Umar Arzu 
Published: August 2016

AbstractWe have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules.
Experiment and simulation of novel liquid crystal plasma mirrors for high contrast, intense laser pulses
Authors: Poole P. L. , Krygier A. , Cochran G. E. , Foster P. S. , Scott G. G. , Wilson L. A. , Bailey J. , Bourgeois N. , Hernandez-Gomez C. , Neely D. , Rajeev P. P. , Freeman R. R. , Schumacher D. W. 
Published: August 2016

AbstractWe describe the first demonstration of plasma mirrors made using freely suspended, ultra-thin films formed dynamically and in-situ. We also present novel particle-in-cell simulations that for the first time incorporate multiphoton ionization and dielectric models that are necessary for describing plasma mirrors. Dielectric plasma mirrors are a crucial component for high intensity laser applications such as ion acceleration and solid target high harmonic generation because they greatly improve pulse contrast. We use the liquid crystal 8CB and introduce an innovative dynamic film formation device that can tune the film thickness so that it acts as its own antireflection coating. Films can be formed at a prolonged, high repetition rate without the need for subsequent realignment. High intensity reflectance above 75% and low-field reflectance below 0.2% are demonstrated, as well as initial ion acceleration experimental results that demonstrate increased ion energy and yield on shots cleaned with these plasma mirrors.
Large fluctuations at the lasing threshold of solid- and liquid-state dye lasers
Authors: Basak Supratim , Blanco Alvaro , López Cefe 
Published: August 2016

AbstractIntensity fluctuations in lasers are commonly studied above threshold in some special configurations (especially when emission is fed back into the cavity or when two lasers are coupled) and related with their chaotic behaviour. Similar fluctuating instabilities are usually observed in random lasers, which are open systems with plenty of quasi-modes whose non orthogonality enables them to exchange energy and provides the sort of loss mechanism whose interplay with pumping leads to replica symmetry breaking. The latter however, had never been observed in plain cavity lasers where disorder is absent or not intentionally added. Here we show a fluctuating lasing behaviour at the lasing threshold both in solid and liquid dye lasers. Above and below a narrow range around the threshold the spectral line-shape is well correlated with the pump energy. At the threshold such correlation disappears, and the system enters a regime where emitted laser fluctuates between narrow, intense and broad, weak peaks. The immense number of modes and the reduced resonator quality favour the coupling of modes and prepares the system so that replica symmetry breaking occurs without added disorder.
Exploration of pathological prediction of chronic kidney diseases by a novel theory of bi-directional probability
Authors: Yang Yuan , Luo Min , Xiao Li , Zhu Xue-jing , Wang Chang , Fu Xiao , Yuan Shu-guang , Xiao Fang , Liu Hong , Dong Zheng , Liu Fu-you , Sun Lin 
Published: August 2016

AbstractIn the clinic, the pathological types of chronic kidney diseases (CKD) are considered references for choosing treatment protocols. From a statistical viewpoint, a non-invasive method to predict pathological types of CKD is a focus of our work. In the current study, following a frequency analysis of the clinical indices of 588 CKD patients in the department of nephrology, a third-grade class-A hospital, a novel theory is proposed: “bi-directional cumulative probability dichotomy”. Further, two models for the prediction and differential diagnosis of CKD pathological type are established. The former indicates an occurrence probability of the pathological types, and the latter indicates an occurrence of CKD pathological type according to logistic binary regression. To verify the models, data were collected from 135 patients, and the results showed that the highest accuracy rate on membranous nephropathy (MN-100%), followed by IgA nephropathy (IgAN-83.33%) and mild lesion type (MLN-73.53%), whereas lower prediction accuracy was observed for mesangial proliferative glomerulonephritis (0%) and focal segmental sclerosis type (21.74%). The models of bi-directional probability prediction and differential diagnosis indicate a good prediction value in MN, IgAN and MLN and may be considered alternative methods for the pathological discrimination of CKD patients who are unable to undergo renal biopsy.
Characterization of mammary epithelial stem/progenitor cells and their changes with aging in common marmosets
Authors: Wu Anqi , Dong Qiaoxiang , Gao Hui , Shi Yuanshuo , Chen Yuanhong , Zhang Fuchuang , Bandyopadhyay Abhik , Wang Danhan , Gorena Karla M. , Huang Changjiang , Tardif Suzette , Nathanielsz Peter W. , Sun Lu-Zhe 
Published: August 2016

AbstractAge is the number one risk factor for breast cancer, yet the underlying mechanisms are unexplored. Age-associated mammary stem cell (MaSC) dysfunction is thought to play an important role in breast cancer carcinogenesis. Non-human primates with their close phylogenetic relationship to humans provide a powerful model system to study the effects of aging on human MaSC. In particular, the common marmoset monkey (Callithrix jacchus) with a relatively short life span is an ideal model for aging research. In the present study, we characterized for the first time the mammary epithelial stem/progenitor cells in the common marmoset. The MaSC-enriched cells formed four major types of morphologically distinct colonies when cultured on plates pre-seeded with irradiated NIH3T3 fibroblasts and were also capable of forming mammospheres in suspension culture and subsequent formation of 3D organoids in Matrigel culture. Most importantly, these 3D organoids were found to contain stem/progenitor cells that can undergo self-renewal and multi-lineage differentiation bothin vitroandin vivo. We also observed a significant decrease of luminal-restricted progenitors with age. Our findings demonstrate that common marmoset mammary stem/progenitor cells can be isolated and quantified with establishedin vitroandin vivoassays used for mouse and human studies.
A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans
Authors: Yang Ruilong , Ren Mingxia , Rui Qi , Wang Dayong 
Published: August 2016

AbstractRecently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231 and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes.
Oxidized (non)-regenerated cellulose affects fundamental cellular processes of wound healing
Authors: Wagenhäuser M. U. , Mulorz J. , Ibing W. , Simon F. , Spin J. M. , Schelzig H. , Oberhuber A. 
Published: August 2016

AbstractIn this study we investigated how hemostats such as oxidized regenerated cellulose (ORC, TABOTAMP) and oxidized non-regenerated cellulose (ONRC, RESORBA CELL) influence local cellular behavior and contraction of the extracellular matrix (ECM). Human stromal fibroblasts were inoculated in vitro with ORC and ONRC. Cell proliferation was assayed over time and migration was evaluated by Live Cell imaging microscopy. Fibroblasts grown in collagen-gels were treated with ORC or ONRC and ECM contraction was measured utilizing a contraction assay. An absolute pH decline was observed with both ORC and ONRC after 1 hour. Mean daily cell proliferation, migration and matrix contraction were more strongly inhibited by ONRC when compared with ORC (p < 0.05). When control media was pH-lowered to match the lower pH values typically seen with ORC and ONRC, significant differences in cell proliferation and migration were still observed between ONRC and ORC (p < 0.05). However, in these pH conditions, inhibition of matrix contraction was only significant for ONRC (p < 0.05). We find that ORC and ONRC inhibit fibroblast proliferation, migration and matrix contraction and stronger inhibition of these essential cellular processes of wound healing were observed for ONRC when compared with ORC. These results will require further validation in future in vivo experiments to clarify the clinical implications for hemostat use in post-surgical wound healing.
Red Mud as an Efficient, Stable and Cost-Free Catalyst for COx-Free Hydrogen Production from Ammonia
Authors: Kurtoğlu Samira Fatma , Uzun Alper 
Published: August 2016

AbstractRed mud, one of the mostly produced industrial wastes, was converted into a catalyst with exceptionally high and stable performance for hydrogen production from ammonia. Results showed that iron species produced after reduction of the HCl digested red mud were converted into ε-Fe2N during the induction period of ammonia decomposition reaction at 700 °C. The catalytic performance measurements indicated that the modified red mud catalyst provides a record high hydrogen production rate for a non-noble metal catalyst at this temperature. For instance, stable hydrogen production rates were measured as 72 and 196 mmol H2 min−1 gcat−1 for the corresponding space velocities of 72 000 and 240 000 cm3 NH3 h−1 gcat−1, respectively, at 700 °C. These results offer opportunities to utilize one of the key hazardous industrial wastes as an eco-friendly, efficient, stable and almost cost-free catalyst for COx-free hydrogen production from ammonia decomposition.
Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells
Authors: Ruiz Silva Mariana , van der Ende-Metselaar Heidi , Mulder H. Lie , Smit Jolanda M. , Rodenhuis-Zybert Izabela A. 
Published: August 2016

AbstractMonocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection.
Impact of membrane lipid composition on the structure and stability of the transmembrane domain of amyloid precursor protein
Authors: Dominguez Laura , Foster Leigh , Straub John E. , Thirumalai D. 
Published: August 2016

Significance
Aggregation of proteins of known sequence is linked to a variety of neurodegenerative disorders. Familial mutations in the amyloid precursor protein (APP), from which the amyloid β (Aβ) protein is excised, are associated with early onset of Alzheimer’s disease. The structures of APP-C99 dimers and the associated stability as well as the monomer–dimer equilibrium are critically influenced by membrane composition. Using a multiscale modeling approach, we have investigated the influence of varying lipid composition on the structure of homodimers of an APP-C99 congener peptide. Besides resolving contradicting experimental results, we demonstrate that membrane lipid composition dramatically influences the relative populations of competing homodimer structures in a way that is linked to the recognition and processing of APP-C99 by γ-secretase.
Electron anions and the glass transition temperature
Authors: Johnson Lewis E. , Sushko Peter V. , Tomota Yudai , Hosono Hideo 
Published: August 2016

Significance
Electrides are ionic materials in which electrons act as anions. Solvated electrons in ammonia are one of the early known examples of such anions in liquids. Electron anions in crystalline materials have previously been shown to dramatically alter their electronic properties, for example, to turn an insulator into a superconductor with minimal changes in the structure and stoichiometry. We show that electron anions modify the disordered glass network by creating highly mobile weak links, thus fundamentally altering the thermodynamic and electronic properties of the network and enabling a new design paradigm for amorphous materials.