bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells
Authors: Ietta Francesca , Maioli Emanuela , Daveri Elena , Gonzaga Oliveira Juliana , da Silva Rafaela José , Romagnoli Roberta , Cresti Laura , Maria Avanzati Anna , Paulesu Luana , Barbosa Bellisa de Freitas , Gomes Angelica de Oliveira , Roberto Mineo José , Ferro Eloisa Amália Vieira 
Published: April 2017

AbstractAutophagy is a crucial and physiological process for cell survival from yeast to mammals, including protozoan parasites. Toxoplasma gondii, an intracellular parasite, typically exploits autophagic machinery of host cell; however host cell upregulates autophagy to combat the infection. Herein we tested the efficacy of Rottlerin, a natural polyphenol with autophagic promoting properties, against Toxoplasma infection on the chorioncarcinoma-derived cell line BeWo. We found that Rottlerin, at sub-toxic doses, induced morphological and biochemical alterations associated with autophagy and decreased Toxoplasma growth in infected cells. Although autophagy was synergically promoted by Toxoplasma infection in combination with Rottlerin treatment, the use of the autophagy inhibitor chloroquine revealed that Rottlerin anti-parasitic effect was largely autophagy-independent and likely mediated by the converging inhibitory effect of Rottlerin and Toxoplasma in host protein translation, mediated by mTOR inhibition and eIF2α phosphorylation. Both events, which on one hand could explain the additive effect on autophagy induction, on the other hand led to inhibition of protein synthesis, thereby depriving Toxoplasma of metabolically essential components for multiplication. We suggest that modulation of the competition between pathogen requirement and host cell defense might be an attractive, novel therapeutic approach against Toxoplasma infection and encourage the development of Rottlerin-based new therapeutic formulations.
Bio-Engineered Graphene-Based Cage for Efficient Local Enrichment and Biodegradation of Aqueous Organic Wastes
Authors: Fan Jixiang , Chen Dongyun , Li Najun , Xu Qingfeng , Li Hua , He Jinghui , Lu Jianmei 
Published: April 2017

AbstractMicroorganism immobilization has attracted great attention as a traditional method to overcome aqueous organic wastes containing N, N-dimethylformamide (DMF). In this approach, graphene oxide was modified with functional polymer firstly to obtain micro-composites material (PGO), and then the prepared composites were deposited on the surface of copper mesh (CM) to block the meshes and CM@PGO was achieved. Moreover, cage-shaped model was designed based on CM@PGO and P. denitrificans was packed inside the cage for batch experiments. This strategy could enrich the local concentration of DMF due to the formation of hydrogen bonds with the oxygen-containing groups from PGO and the character of bacteria in captivity could also contribute to the process of degradation. Results showed that the approach could remove DMF more efficiently about 15% compared with free microorganism and presented excellent cycling performance. Meantime, physical adsorption and chemical adsorption were both contributed to the process of PGO adsorption, and the adsorption isotherm fits Langmuir model well, furthermore, the theoretical maximum of adsorption ability calculated through Langmuir model is 95 mg/g. In other words, this cage-shaped CM@PGO provided a facile platform for treating various wastewaters by altering the species of packed microorganisms, which exhibited considerable prospects for wastewater treatment.
Label-free isolation of prostate circulating tumor cells using Vortex microfluidic technology
Authors: Renier Corinne , Pao Edward , Che James , Liu Haiyan E. , Lemaire Clementine A. , Matsumoto Melissa , Triboulet Melanie , Srivinas Sandy , Jeffrey Stefanie S. , Rettig Matthew , Kulkarni Rajan P. , Di Carlo Dino , Sollier-Christen Elodie 
Published: April 2017

AbstractThere has been increased interest in utilizing non-invasive “liquid biopsies” to identify biomarkers for cancer prognosis and monitoring, and to isolate genetic material that can predict response to targeted therapies. Circulating tumor cells (CTCs) have emerged as such a biomarker providing both genetic and phenotypic information about tumor evolution, potentially from both primary and metastatic sites. Currently, available CTC isolation approaches, including immunoaffinity and size-based filtration, have focused on high capture efficiency but with lower purity and often long and manual sample preparation, which limits the use of captured CTCs for downstream analyses. Here, we describe the use of the microfluidic Vortex Chip for size-based isolation of CTCs from 22 patients with advanced prostate cancer and, from an enumeration study on 18 of these patients, find that we can capture CTCs with high purity (from 1.74 to 37.59%) and efficiency (from 1.88 to 93.75 CTCs/7.5 mL) in less than 1 h. Interestingly, more atypical large circulating cells were identified in five age-matched healthy donors (46–77 years old; 1.25–2.50 CTCs/7.5 mL) than in five healthy donors <30 years old (21–27 years old; 0.00 CTC/7.5 mL). Using a threshold calculated from the five age-matched healthy donors (3.37 CTCs/mL), we identified CTCs in 80% of the prostate cancer patients. We also found that a fraction of the cells collected (11.5%) did not express epithelial prostate markers (cytokeratin and/or prostate-specific antigen) and that some instead expressed markers of epithelial–mesenchymal transition, i.e., vimentin and N-cadherin. We also show that the purity and DNA yield of isolated cells is amenable to targeted amplification and next-generation sequencing, without whole genome amplification, identifying unique mutations in 10 of 15 samples and 0 of 4 healthy samples.
Oxoaporphine Metal Complexes (CoII, NiII, ZnII) with High Antitumor Activity by Inducing Mitochondria-Mediated Apoptosis and S-phase Arrest in HepG2
Authors: Qin Jiao-Lan , Shen Wen-Ying , Chen Zhen-Feng , Zhao Li-Fang , Qin Qi-Pin , Yu Yan-Cheng , Liang Hong 
Published: April 2017

AbstractThree new oxoaporphine Co(II), Ni(II) and Zn(II) complexes 1–3 have been synthesized and fully characterized. 1–3 have similar mononuclear structures with the metal and ligand ratio of 1:2. 1–3 exhibited higher cytotoxicity than the OD ligand and cisplatin against HepG2, T-24, BEL-7404, MGC80–3 and SK-OV-3/DDP cells, with IC50 value of 0.23−4.31 μM. Interestingly, 0.5 μM 1–3 significantly caused HepG2 arrest at S-phase, which was associated with the up-regulation of p53, p21, p27, Chk1 and Chk2 proteins, and decrease in cyclin A, CDK2, Cdc25A, PCNA proteins. In addition, 1–3 induced HepG2 apoptosis via a caspase-dependent mitochondrion pathway as evidenced by p53 activation, ROS production, Bax up-regulation and Bcl-2 down-regulation, mitochondrial dysfunction, cytochrome c release, caspase activation and PARP cleavage. Furthermore, 3 inhibited tumor growth in HepG2 xenograft model, and displayed more safety profile in vivo than cisplatin.
Prediction of intraventricular haemorrhage in preterm infants using time series analysis of blood pressure and respiratory signals
Authors: Huvanandana Jacqueline , Nguyen Chinh , Thamrin Cindy , Tracy Mark , Hinder Murray , McEwan Alistair L. 
Published: April 2017

AbstractDespite the decline in mortality rates of extremely preterm infants, intraventricular haemorrhage (IVH) remains common in survivors. The need for resuscitation and cardiorespiratory management, particularly within the first 24 hours of life, are important factors in the incidence and timing of IVH. Variability analyses of heart rate and blood pressure data has demonstrated potential approaches to predictive monitoring. In this study, we investigated the early identification of infants at a high risk of developing IVH, using time series analysis of blood pressure and respiratory data. We also explore approaches to improving model performance, such as the inclusion of multiple variables and signal pre-processing to enhance the results from detrended fluctuation analysis. Of the models we evaluated, the highest area under receiver-operator characteristic curve (5th, 95th percentile) achieved was 0.921 (0.82, 1.00) by mean diastolic blood pressure and the long-term scaling exponent of pulse interval (PI α2), exhibiting a sensitivity of >90% at a specificity of 75%. Following evaluation in a larger population, our approach may be useful in predictive monitoring to identify infants at high risk of developing IVH, offering caregivers more time to adjust intensive care treatment.
Nontuberculous mycobacteria in gastrostomy fed patients with cystic fibrosis
Authors: Al-momani H. , Perry A. , Jones R. , Bourke S. , Doe S. , Perry J. , Anderson A. , Forrest T. , Forrest I. , Griffin M. , Brodlie M. , Pearson J. , Ward C. 
Published: April 2017

AbstractMulti-drug resistant Mycobacterium abscessus complex (MABSC) is a form of Nontuberculous mycobacteria (NTM) of special, international concern in Cystic Fibrosis (CF). We hypothesised that gastric juice and percutaneous endoscopic gastrostomy (PEG) feeding devices might yield MABSC isolates. Gastric juice and sputa from sixteen adult PEG fed CF patients and five replaced PEG tubes were studied. Bacterial and fungal isolates were cultured. Mycobacterium were identified by rpoB, sodA and hsp65 gene sequencing and strain typed using variable number tandem repeat. Bacteria and/or fungi grew from all gastric juice, sputa and PEG samples. MABSC were detected in 7 patients. Five had MABSC in their sputum. Two had an identical MABSC strain in their sputum and gastric juice and one had the same strain isolated from their PEG tube and sputum. Two patients who were sputum sample negative had MABSC isolated in their gastric juice or PEG tube. MABSC were therefore identified for the first time from a gastric sample in a minority of patients. We conclude that gastric juice and PEG-tubes may be a potential source of MABSC isolates in CF patients, and these findings warrant further study.
Relation between molecular electronic structure and nuclear spin-induced circular dichroism
Authors: Štěpánek Petr , Coriani Sonia , Sundholm Dage , Ovchinnikov Vasily A. , Vaara Juha 
Published: April 2017

AbstractThe recently theoretically described nuclear spin-induced circular dichroism (NSCD) is a promising method for the optical detection of nuclear magnetization. NSCD involves both optical excitations of the molecule and hyperfine interactions and, thus, it offers a means to realize a spectroscopy with spatially localized, high-resolution information. To survey the factors relating the molecular and electronic structure to the NSCD signal, we theoretically investigate NSCD of twenty structures of the four most common nucleic acid bases (adenine, guanine, thymine, cytosine). The NSCD signal correlates with the spatial distribution of the excited states and couplings between them, reflecting changes in molecular structure and conformation. This constitutes a marked difference to the nuclear magnetic resonance (NMR) chemical shift, which only reflects the local molecular structure in the ground electronic state. The calculated NSCD spectra are rationalized by means of changes in the electronic density and by a sum-over-states approach, which allows to identify the contributions of the individual excited states. Two separate contributions to NSCD are identified and their physical origins and relative magnitudes are discussed. The results underline NSCD spectroscopy as a plausible tool with a power for the identification of not only different molecules, but their specific structures as well.
Curcumol allosterically modulates GABA(A) receptors in a manner distinct from benzodiazepines
Authors: Liu Yan-Mei , Fan Hui-Ran , Ding Jing , Huang Chen , Deng Shining , Zhu Tailin , Xu Tian-Le , Ge Wei-Hong , Li Wei-Guang , Li Fei 
Published: April 2017

AbstractInhibitory A type γ-aminobutyric acid receptors (GABAARs) play a pivotal role in orchestrating various brain functions and represent an important molecular target in neurological and psychiatric diseases, necessitating the need for the discovery and development of novel modulators. Here, we show that a natural compound curcumol, acts as an allosteric enhancer of GABAARs in a manner distinct from benzodiazepines. Curcumol markedly facilitated GABA-activated currents and shifted the GABA concentration-response curve to the left in cultured hippocampal neurons. When co-applied with the classical benzodiazepine diazepam, curcumol further potentiated GABA-induced currents. In contrast, in the presence of a saturating concentration of menthol, a positive modulator for GABAAR, curcumol failed to further enhance GABA-induced currents, suggesting shared mechanisms underlying these two agents on GABAARs. Moreover, the benzodiazepine antagonist flumazenil did not alter the enhancement of GABA response by curcumol and menthol, but abolished that by DZP. Finally, mutations at the β2 or γ2 subunit predominantly eliminated modulation of recombinant GABAARs by curcumol and menthol, or diazepam, respectively. Curcumol may therefore exert its actions on GABAARs at sites distinct from benzodiazepine sites. These findings shed light on the future development of new therapeutics drugs targeting GABAARs.
Identification of risk factors in epidemiologic study based on ROC curve and network
Authors: Jin Jiao , Zhou Shixin , Xu Qiujin , An Jinbing 
Published: April 2017

AbstractThis article proposes a new non-parametric approach for identification of risk factors and their correlations in epidemiologic study, in which investigation data may have high variations because of individual differences or correlated risk factors. First, based on classification information of high or low disease incidence, we estimate Receptor Operating Characteristic (ROC) curve of each risk factor. Then, through the difference between ROC curve of each factor and diagonal, we evaluate and screen for the important risk factors. In addition, based on the difference of ROC curves corresponding to any pair of factors, we define a new type of correlation matrix to measure their correlations with disease, and then use this matrix as adjacency matrix to construct a network as a visualization tool for exploring the structure among factors, which can be used to direct further studies. Finally, these methods are applied to analysis on water pollutants and gastrointestinal tumor, and analysis on gene expression data in tumor and normal colon tissue samples.
Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients
Authors: Chiappini Franck , Coilly Audrey , Kadar Hanane , Gual Philippe , Tran Albert , Desterke Christophe , Samuel Didier , Duclos-Vallée Jean-Charles , Touboul David , Bertrand-Michel Justine , Brunelle Alain , Guettier Catherine , Le Naour François 
Published: April 2017

AbstractNonalcoholic steatohepatitis (NASH) is a condition which can progress to cirrhosis and hepatocellular carcinoma. Markers for NASH diagnosis are still lacking. We performed a comprehensive lipidomic analysis on human liver biopsies including normal liver, nonalcoholic fatty liver and NASH. Random forests-based machine learning approach allowed characterizing a signature of 32 lipids discriminating NASH with 100% sensitivity and specificity. Furthermore, we validated this signature in an independent group of NASH patients. Then, metabolism dysregulations were investigated in both patients and murine models. Alterations of elongase and desaturase activities were observed along the fatty acid synthesis pathway. The decreased activity of the desaturase FADS1 appeared as a bottleneck, leading upstream to an accumulation of fatty acids and downstream to a deficiency of long-chain fatty acids resulting to impaired phospholipid synthesis. In NASH, mass spectrometry imaging on tissue section revealed the spreading into the hepatic parenchyma of selectively accumulated fatty acids. Such lipids constituted a highly toxic mixture to human hepatocytes. In conclusion, this study characterized a specific and sensitive lipid signature of NASH and positioned FADS1 as a significant player in accumulating toxic lipids during NASH progression.
How voluntary orienting of attention and alerting modulate costs of conflict processing
Authors: Zani Alberto , Proverbio Alice Mado 
Published: April 2017

AbstractThere is evidence that pre-cued valid orienting of attention to competing information diminishes costs of brain processing of conflict. Still unclear, because scantily addressed by neuroimaging studies and mostly analyzed by means of behavioral indexing, it is whether conflict undergoes an equivalent modulation by tonic and pre-cued phasic alerting. Here, we investigated the functional relationships between attention orienting, alerting and executive systems using the Attention Network Test (ANT). Both reaction times (RTs) and ERPs were recorded. In line with previous literature, results showed that both RTs and a so-called ERPs conflict negativity (CN), prominent at anterior scalp and indexing conflict processing, were positively modulated by a prior valid orienting of attention onto the location of conflicting stimuli. Indeed, in this condition both kinds of markers showed faster latencies, while CN also reached higher amplitude values than in both alerting conditions, and, in turn, in pre-cued phasic alerting than in uncued tonic alerting. Moreover, while CN was larger over the right hemisphere independent of functional conditions, it was strongly modulated by the latter over the left hemisphere. Our ERP findings support the views of conflict modulation by both orienting and phasic alerting and of a functional integration between attentional brain networks.
Phosphatidylethanolamine dynamics are required for osteoclast fusion
Authors: Irie Atsushi , Yamamoto Kei , Miki Yoshimi , Murakami Makoto 
Published: April 2017

AbstractOsteoclasts, responsible for bone resorption, are multinucleated cells formed by cell-cell fusion of mononuclear pre-osteoclasts. Although osteoclast fusion is a pivotal step for osteoclastogenesis, little is known about the mechanism involved. To clarify the underlying process, we investigated dynamics of membrane phospholipids during osteoclastogenesisin vitro.We found that the cellular content of phospholipids, phosphatidylethanolamine (PE) in particular, was increased during osteoclast differentiation. Furthermore, PE was greatly increased in the outer leaflet of the plasma membrane bilayer during osteoclastogenesis, being concentrated in filopodia involved in cell-cell fusion. Immobilisation of the cell surface PE blocked osteoclast fusion, revealing the importance of PE abundance and distribution. To identify the molecules responsible for these PE dynamics, we screened a wide array of lipid-related genes by quantitative PCR and shRNA-mediated knockdown. Among them, a PE-biosynthetic enzyme, acyl-CoA:lysophosphatidylethanolamine acyltransferase 2 (LPEAT2), and two ATP-binding cassette (ABC) transporters, ABCB4 and ABCG1, were markedly increased during osteoclastogenesis, and their knockdown in pre-osteoclasts led to reduction in PE exposure on the cell surface and subsequent osteoclast fusion. These findings demonstrate that the PE dynamics play an essential role in osteoclast fusion, in which LPEAT2, ABCB4 and ABCG1 are key players for PE biosynthesis and redistribution.
Fasciola hepatica glycoconjugates immuneregulate dendritic cells through the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin inducing T cell anergy
Authors: Rodríguez Ernesto , Kalay Hakan , Noya Verónica , Brossard Natalie , Giacomini Cecilia , van Kooyk Yvette , García-Vallejo Juan J. , Freire Teresa 
Published: April 2017

AbstractDendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) expressed on a variety of DCs, is a C-type lectin receptor that recognizes glycans on a diverse range of pathogens, including parasites. The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whetherF. hepaticaglycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts withF. hepaticaglycoconjugates through mannose and fucose residues. We also show that mannose is present in high-mannose structures, hybrid and trimannosyl N-glycans with terminal GlcNAc. Furthermore, we demonstrate thatF. hepaticaglycans induce DC-SIGN triggering leading to a strong production of TLR-induced IL-10 and IL-27p28. In addition, parasite glycans induced regulatory DCs via DC-SIGN that decrease allogeneic T cell proliferation, via the induction of anergic/regulatory T cells, highlighting the role of DC-SIGN in the regulation of innate and adaptive immune responses byF. hepatica. Our data confirm the immunomodulatory properties of DC-SIGN triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.
The Clinical Efficacy of Fibrinogen Concentrate in Massive Obstetric Haemorrhage with Hypofibrinogenaemia
Authors: Matsunaga Shigetaka , Takai Yasushi , Nakamura Eishin , Era Sumiko , Ono Yoshihisa , Yamamoto Koji , Maeda Hiroo , Seki Hiroyuki 
Published: April 2017

AbstractMassive obstetric haemorrhage remains a major cause of maternal death attributable to hypofibrinogenaemia. Transfusion of large volumes of fresh frozen plasma (FFP) is required to normalise fibrinogen levels. We compared the efficacy of FFP (F group) with that of FFP plus fibrinogen concentrate (F + F group) in massive obstetric haemorrhage. In this retrospective study, we compared the medical charts (2004–2016) of 137 patients with <150 mg/dl fibrinogen treated with F + F (n = 47; after August 2009) or F (n = 56; before August 2009). Although fibrinogen concentrate was only administered in severe cases, the FFP/red blood cell concentrate (RCC) ratio was significantly lower in the F + F group than in the F group. A sub-group analysis of cases requiring ≥18 RCC units showed that the F + F group received significantly less FFP than the F group (40.2 ± 19.6 versus 53.4 ± 18.5 units; P = 0.047) and showed significantly less pulmonary oedema (24.0% vs 57.1%; P < 0.05) in the absence of any significant differences in pre-transfusion coagulation, estimated blood loss, or RCC transfusion volume. Administration of fibrinogen concentrate increased the rate of fibrinogen supplementation five-fold and reduced FFP dosage, the FFP/RCC ratio, and the incidence of pulmonary oedema.
A Novel Method to Evaluate Ribosomal Performance in Cell-Free Protein Synthesis Systems
Authors: Kempf Noémie , Remes Cristina , Ledesch Ralph , Züchner Tina , Höfig Henning , Ritter Ilona , Katranidis Alexandros , Fitter Jörg 
Published: April 2017

AbstractCell-free protein synthesis (CFPS) systems were designed to produce proteins with a minimal set of purified components, thus offering the possibility to follow translation as well as protein folding. In order to characterize the performance of the ribosomes in such a system, it is crucial to separately quantify the two main components of productivity, namely the fraction of active ribosomes and the number of synthesizing cycles. Here, we provide a direct and highly reliable measure of ribosomal activity in any given CFPS system, introducing an enhanced-arrest peptide variant. We observe an almost complete stalling of ribosomes that produce GFPem (~95%), as determined by common centrifugation techniques and fluorescence correlation spectroscopy (FCS). Moreover, we thoroughly study the effect of different ribosomal modifications independently on activity and number of synthesizing cycles. Finally, employing two-colour coincidence detection and two-colour colocalisation microscopy, we demonstrate real-time access to key productivity parameters with minimal sample consumption on a single ribosome level.