bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent Regulation of Actin Dynamics and Megakaryoblastic Leukemia-1 and -2 (Mkl1/2) by cAMP in Endothelial and Smooth Muscle Cells
Authors: Smith Madeleine C. , Hudson Claire A. , Kimura Tomomi E. , White Stephen J. , Sala-Newby Graciela B. , Newby Andrew C. , Bond Mark 
Published: June 2017

AbstractProliferation and migration of vascular smooth muscle cells (VSMCs) or endothelial cell (ECs) promote or inhibit, respectively, restenosis after angioplasty, vein graft intimal thickening and atherogenesis. Here we investigated the effects of cAMP-induced cytoskeletal remodelling on the serum response factor (SRF) co-factors Megakaryoblastic Leukemia-1 and -2 (MKL1 and MKL2) and their role in controlling VSMC and EC proliferation and migration. Elevation of cAMP using forskolin, dibutyryl-cAMP (db-cAMP), BAY60-6583 or Cicaprost induced rapid cytoskeleton remodelling and inhibited proliferation and migration in VSMCs but not EC. Furthermore, elevated cAMP inhibited mitogen-induced nuclear-translocation of MKL1 and MKL2 in VSMCs but not ECs. Forskolin also significantly inhibited serum response factor (SRF)-dependent reporter gene (SRE-LUC) activity and mRNA expression of pro-proliferative and pro-migratory MKL1/2 target genes in VSMCs but not in ECs. In ECs, MKL1 was constitutively nuclear and MKL2 cytoplasmic, irrespective of mitogens or cAMP. Pharmacological or siRNA inhibition of MKL1 significantly inhibited the proliferation and migration of VSMC and EC. Our new data identifies and important contribution of MKL1/2 to explaining the strikingly different response of VSMCs and ECs to cAMP elevation. Elucidation of these pathways promises to identify targets for specific inhibition of VSMC migration and proliferation.
Rapid discrimination of human oesophageal squamous cell carcinoma by mass spectrometry based on differences in amino acid metabolism
Authors: Jianyong Zhang , Jianjun Xu , Yongzhong Ouyang , Junwen Liu , Haiyan Lu , Dongliang Yu , Jinhua Peng , Junwen Xiong , Huanwen Chen , Yiping Wei 
Published: June 2017

AbstractOesophageal cancer (OC) is associated with high morbidity and mortality, and surgery is the most effective approach to treat it. In order to reduce surgical risks and duration of surgery, we explored a new strategy to determine tumour margins in surgery. In this study, we included 128 cancerous and 128 noncancerous database entries obtained from 32 human patients. Using internal extractive electrospray ionization-MS, in positive ion detection mode, the relative abundances of m/z 104.13, m/z 116.10, m/z 132.13, and m/z 175.13 were higher in cancer tissue while the relative abundances of m/z 82.99, m/z 133.11, m/z 147.08, m/z 154.06, and m/z 188.05 were higher in normal tissue. Using partial least squares analysis, the mass spectra of cancer samples was discriminated from those of normal tissues, and the discriminatory ions were obtained from loading plots. Dimethylglycine(m/z 104), proline(m/z 116), isoleucine(m/z 132), asparagine(m/z 133), glutamine(m/z 147), and arginine(m/z 175) were identified by collision-induced dissociation experiments. Using the ROC curve analysis, we verified the validity of six amino acids for the identification of tumour tissue. Further investigations of tissue amino acids may allow us to better understand the underlying mechanisms involved in OC and develop novel means to identify tumour tissue during operation.
Effects of high CD4 cell counts on death and attrition among HIV patients receiving antiretroviral treatment: an observational cohort study
Authors: Tang Zhenzhu , Pan Stephen W. , Ruan Yuhua , Liu Xuanhua , Su Jinming , Zhu Qiuying , Shen Zhiyong , Zhang Heng , Chen Yi , Lan Guanghua , Xing Hui , Liao Lingjie , Feng Yi , Shao Yiming 
Published: June 2017

AbstractCurrent WHO guidelines recommend initiating ART regardless of CD4+ cell count. In response, we conducted an observational cohort study to assess the effects of pre-ART CD4+ cell count levels on death, attrition, and death or attrition in HIV treated patients. This large HIV treatment cohort study (n = 49,155) from 2010 to 2015 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between pre-ART CD4+ cell counts and death, attrition, and death or attrition. The average mortality and ART attrition rates among all treated patients were 2.63 deaths and 5.32 attritions per 100 person-years, respectively. Compared to HIV patients with <350 CD4+ cells/mm3 at ART initiation, HIV patients with >500 CD4+ cells/mm3 at ART initiation had a significantly lower mortality rate (Adjusted hazard ratio: 0.56, 95% CI: 0.40–0.79), but significantly higher ART attrition rate (AHR: 1.17, 95% CI: 1.03–1.33). Results from this study suggest that HIV patients with high CD4+ cell counts at the time of ART initiation may be at greater risk of treatment attrition. To further reduce ART attrition, it is imperative that patient education and healthcare provider training on ART adherence be enhanced and account for CD4 levels at ART initiation.
Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells
Authors: Lee Young-Sun , Kim So Yeon , Ko Eunjung , Lee Jun-Hee , Yi Hyon-Seung , Yoo Yang Jae , Je Jihye , Suh Sang Jun , Jung Young Kul , Kim Ji Hoon , Seo Yeon Seok , Yim Hyung Joon , Jeong Won-Il , Yeon Jong Eun , Um Soon Ho , Byun Kwan Soo 
Published: June 2017

AbstractNon-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes. Compared with controls, PA-treated hepatocytes displayed significantly increased CD36 and exosome production. The microarray analysis showed there to be distinctive miRNA expression patterns between exosomes from vehicle- and PA-treated hepatocytes. When LX-2 cells were cultured with exosomes from PA-treated hepatocytes, the expression of genes related to the development of fibrosis were significantly amplified compared to those treated with exosomes from vehicle-treated hepatocytes. In conclusion, PA treatment enhanced the production of exosomes in these hepatocytes and changed their exosomal miRNA profile. Moreover, exosomes derived from PA-treated hepatocytes caused an increase in the expression levels of fibrotic genes in HSCs. Therefore, exosomes may have important roles in the crosstalk between hepatocytes and HSCs in the progression from simple steatosis to NASH.
Investigation of the 2312 flexoelectric coefficient component of polyvinylidene fluoride: Deduction, simulation, and mensuration
Authors: Zhang Shuwen , Liu Kaiyuan , Xu Minglong , Shen Hao , Chen Kai , Feng Bo , Shen Shengping 
Published: June 2017

AbstractFlexoelectric effects hold promising applications in sensing, actuating, and energy capturing, and thus it is demanded to measure the flexoelectric coefficient tensors of dielectric materials accurately. In this work, an approach to measuring the effective flexoelectric coefficient tensor component μ2312 of polymeric materials is developed by imposing a torque load upon a half cylindrical specimen. It is proven that μ2312 can be calculated by assessing the electric charge on the axial plane and the strain gradient along the radial direction, both induced by the torque. To overcome the difficulty in experimental measurements, the relationship between the strain gradient and torque is deduced theoretically and further verified with finite element analysis. This approach is applied to testing bars machined from bulk polyvinylidene fluoride (PVDF). Potential errors from the piezoelectric effects and the non-uniform strain gradient are discussed to verify the validity of the measurement. The experimental results show good reproducibility and agreement with other measured effective flexoelectric tensor components of PVDF. This work indicates a potential application of PVDF-based mechanical sensors and provides a method to investigate the effective flexoelectric coefficient component of polymers.
Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections
Authors: Presta Luana , Bosi Emanuele , Mansouri Leila , Dijkshoorn Lenie , Fani Renato , Fondi Marco 
Published: June 2017

AbstractAcinetobacter baumannii is a clinical threat to human health, causing major infection outbreaks worldwide. As new drugs against Gram-negative bacteria do not seem to be forthcoming, and due to the microbial capability of acquiring multi-resistance, there is an urgent need for novel therapeutic targets. Here we have derived a list of new potential targets by means of metabolic reconstruction and modelling of A. baumannii ATCC 19606. By integrating constraint-based modelling with gene expression data, we simulated microbial growth in normal and stressful conditions (i.e. following antibiotic exposure). This allowed us to describe the metabolic reprogramming that occurs in this bacterium when treated with colistin (the currently adopted last-line treatment) and identify a set of genes that are primary targets for developing new drugs against A. baumannii, including colistin-resistant strains. It can be anticipated that the metabolic model presented herein will represent a solid and reliable resource for the future treatment of A. baumannii infections.
In Vivo Quantification of Placental Insufficiency by BOLD MRI: A Human Study
Authors: Luo Jie , Abaci Turk Esra , Bibbo Carolina , Gagoski Borjan , Roberts Drucilla J. , Vangel Mark , Tempany-Afdhal Clare M. , Barnewolt Carol , Estroff Judy , Palanisamy Arvind , Barth William H. , Zera Chloe , Malpica Norberto , Golland Polina , Adalsteinsson Elfar , Robinson Julian N. , Grant Patricia Ellen 
Published: June 2017

AbstractFetal health is critically dependent on placental function, especially placental transport of oxygen from mother to fetus. When fetal growth is compromised, placental insufficiency must be distinguished from modest genetic growth potential. If placental insufficiency is present, the physician must trade off the risk of prolonged fetal exposure to placental insufficiency against the risks of preterm delivery. Current ultrasound methods to evaluate the placenta are indirect and insensitive. We propose to use Blood-Oxygenation-Level-Dependent (BOLD) MRI with maternal hyperoxia to quantitatively assess mismatch in placental function in seven monozygotic twin pairs naturally matched for genetic growth potential. In-utero BOLD MRI time series were acquired at 29 to 34 weeks gestational age. Maps of oxygen Time-To-Plateau (TTP) were obtained in the placentas by voxel-wise fitting of the time series. Fetal brain and liver volumes were measured based on structural MR images. After delivery, birth weights were obtained and placental pathological evaluations were performed. Mean placental TTP negatively correlated with fetal liver and brain volumes at the time of MRI as well as with birth weights. Mean placental TTP positively correlated with placental pathology. This study demonstrates the potential of BOLD MRI with maternal hyperoxia to quantify regional placental function in vivo.
Molecular Identification of Multiple Antibiotic Resistant Fish Pathogenic Enterococcus faecalis and their Control by Medicinal Herbs
Authors: Rahman Muntasir , Rahman Md. Mahbubur , Deb Suzan Chandra , Alam Md. Shahanoor , Alam Md. Jahangir , Islam Md. Tofazzal 
Published: June 2017

AbstractThe opportunistic fish pathogen, Enterococcus faecalis has been reported to cause mass mortality in several fish species in different countries. The objectives of this study were to (i) identify E. faecalis from the diseased fishes through molecular techniques; (ii) assess the antibiotic susceptibility profile of E. faecalis isolates; and (iii) control disease in tilapia fish by treatment with medicinal plant extracts. A total of 48 isolates were phenotypically identified as Enterococcus species from tilapia, stinging catfish and walking catfish cultivated in several fish farms in Gazipur. Ten randomly selected isolates were identified as E.faecalis by 16S rRNA gene sequencing. Artificial infection revealed that most of the isolates caused moderate to high mortality in fishes with characteristic disease symptoms. These isolates exhibited resistance to multiple antibiotics in vitro. Bioassay revealed that organic extracts of Tamarindus indica and Emblica officinalis leaves, Allium sativum bulb, and Syzygium aromaticum bud inhibited the growth of E. faecalis. Methanol extracts of A. sativum and methanol and acetone extracts of S. aromaticum significantly reduced the mortality of fish artificially infected with E. faecalis as both preventive and therapeutic agents. This is the first report on molecular identification, and herbal control of fish pathogenic E. faecalis in Bangladesh.
Preparation of core-shell structure KClO4@Al/CuO Nanoenergetic material and enhancement of thermal behavior
Authors: Yang Fan , Kang Xiaoli , Luo Jiangshan , Yi Zao , Tang Yongjian 
Published: June 2017

AbstractIn this paper, a solvent/non-solvent synthetic approach has been utilized in preparing a new nanoenergetic material KClO4@Al/CuO by coating Al/CuO nanocomposites particles with a layer of nanoscale oxidizer KClO4. The coating process and mechanism are discussed. The composites of Al/CuO are uniformly mixed by mechanical ball milling process and CuO acts as a catalytic metallic oxide. The ternary mixtures KClO4@Al/CuO were characterized by X-ray diffraction (XRD) and the results reveal that after ball-milling and chemical synthesis process, the phase compositions haven’t changed. Scan electron microscopy (SEM) images show that these energetic nanocomposites consist of small clusters of Al/CuO that are in intimate contact with a continuous and clear-cut KClO4 layer (100–400 nm). In a Scanning transmission electron microscopy (STEM) elemental map, high K/Cl intensity on the perimeter of the nanoparticles and high Cu/Al content in the interior powerfully demonstrated the KClO4@Al/CuO core-shell nanostructure. Electrical ignition experiments and pressure cell test prove that these nanoenergetic composites are more sensitive to ignition with much higher burning rate than traditional formulations (conventional counterparts). To quantify the enhancement of thermal behavior, Thermogravimetry (TG) and Differential scanning calorimetry (DSC) were performed and the results show that the burning rate of these energetic nanocomposites nearly tripled.
Fibronectin promotes directional persistence in fibroblast migration through interactions with both its cell-binding and heparin-binding domains
Authors: Missirlis Dimitris , Haraszti Tamás , Kessler Horst , Spatz Joachim P. 
Published: June 2017

AbstractThe precise mechanisms through which insoluble, cell-adhesive ligands induce and regulate directional cell migration remain obscure. We recently demonstrated that elevated surface density of physically adsorbed plasma fibronectin (FN) promotes high directional persistence in fibroblast migration. While cell-FN association through integrins α5β1and αvβ3was necessary, substrates that selectively engaged these integrins did not support the phenotype. We here show that high directional persistence necessitates a combination of the cell-binding and C-terminal heparin-binding domains of FN, but does not require the engagement of syndecan-4 or integrin α4β1. FN treatment with various fixation agents indicated that associated changes in fibroblast motility were due to biochemical changes, rather than alterations in its physical state. The nature of the coating determined the ability of fibroblasts to assemble endogenous or exogenous FN, while FN fibrillogenesis played a minor, but significant, role in regulating directionality. Interestingly, knockdown of cellular FN abolished cell motility altogether, demonstrating a requirement for intracellular processes in enabling fibroblast migration on FN. Lastly, kinase inhibition experiments revealed that regulation of cell speed and directional persistence are decoupled. Hence, we have identified factors that render full-length FN a promoter of directional migration and discuss the possible, relevant mechanisms.
Structural Characterization of the SMRT Corepressor Interacting with Histone Deacetylase 7
Authors: Desravines Danielle C. , Serna Martin Itziar , Schneider Robert , Mas Philippe J. , Aleksandrova Nataliia , Jensen Malene Ringkjøbing , Blackledge Martin , Hart Darren J. 
Published: June 2017

AbstractThe 2525 amino acid SMRT corepressor is an intrinsically disordered hub protein responsible for binding and coordinating the activities of multiple transcription factors and chromatin modifying enzymes. Here we have studied its interaction with HDAC7, a class IIa deacetylase that interacts with the corepressor complex together with the highly active class I deacetylase HDAC3. The binding site of class IIa deacetylases was previously mapped to an approximate 500 amino acid region of SMRT, with recent implication of short glycine-serine-isoleucine (GSI) containing motifs. In order to characterize the interaction in detail, we applied a random library screening approach within this region and obtained a range of stable, soluble SMRT fragments. In agreement with an absence of predicted structural domains, these were characterized as intrinsically disordered by NMR spectroscopy. We identified one of them, comprising residues 1255–1452, as interacting with HDAC7 with micromolar affinity. The binding site was mapped in detail by NMR and confirmed by truncation and alanine mutagenesis. Complementing this with mutational analysis of HDAC7, we show that HDAC7, via its surface zinc ion binding site, binds to a 28 residue stretch in SMRT comprising a GSI motif followed by an alpha helix.
Super-resolution microscopy with very large working distance by means of distributed aperture illumination
Authors: Birk Udo , Hase Johann v. , Cremer Christoph 
Published: June 2017

AbstractThe limits of conventional light microscopy (“Abbe-Limit“) depend critically on the numerical aperture (NA) of the objective lens. Imaging at large working distances or a large field-of-view typically requires low NA objectives, thereby reducing the optical resolution to the multi micrometer range. Based on numerical simulations of the intensity field distribution, we present an illumination concept for a super-resolution microscope which allows a three dimensional (3D) optical resolution around 150 nm for working distances up to the centimeter regime. In principle, the system allows great flexibility, because the illumination concept can be used to approximate the point-spread-function of conventional microscope optics, with the additional benefit of a customizable pupil function. Compared with the Abbe-limit using an objective lens with such a large working distance, a volume resolution enhancement potential in the order of 104 is estimated.
Towards Printable Natural Dielectric Cloaks via Inverse Scattering Techniques
Authors: Di Donato Loreto , Isernia Tommaso , Labate Giuseppe , Matekovits Ladislau 
Published: June 2017

AbstractThe synthesis of non-magnetic 2D dielectric cloaks as proper solutions of an inverse scattering problem is addressed in this paper. Adopting the relevant integral formulation governing the scattering phenomena, analytic and numerical approaches are exploited to provide new insights on how frequency and direction of arrival of the incoming wave may influence the cloaking mechanism in terms of permittivity distribution within the cover region. In quasi-static (subwavelength) regime a solution is analytically derived in terms of homogeneous artificial dielectric cover with ε < ε0, which is found to be a necessary and sufficient condition for achieving omnidirectional cloaking. On the other hand, beyond quasi-static regime, the cloaking problem is addressed as an optimization task looking for only natural dielectric coatings with ε > ε0 able to hide the object for a given number of directions of the incident field. Simulated results confirm the validity of both analytic and numerical methodologies and allow to estimate effective bandwidths both in terms of frequency range and direction of arrival of the impinging field.
Allosteric modulatory effects of SRI-20041 and SRI-30827 on cocaine and HIV-1 Tat protein binding to human dopamine transporter
Authors: Sun Wei-Lun , Quizon Pamela M. , Yuan Yaxia , Zhang Wei , Ananthan Subramaniam , Zhan Chang-Guo , Zhu Jun 
Published: June 2017

AbstractDopamine transporter (DAT) is the target of cocaine and HIV-1 transactivator of transcription (Tat) protein. Identifying allosteric modulatory molecules with potential attenuation of cocaine and Tat binding to DAT are of great scientific and clinical interest. We demonstrated that tyrosine 470 and 88 act as functional recognition residues in human DAT (hDAT) for Tat-induced inhibition of DA transport and transporter conformational transitions. Here we investigated the allosteric modulatory effects of two allosteric ligands, SRI-20041 and SRI-30827 on cocaine binding on wild type (WT) hDAT, Y470 H and ﻿Y﻿88 F mutants. Effect of SRI-30827 on Tat-induced inhibition of [3H]WIN35,428 binding was also determined. Compared to a competitive DAT inhibitor indatraline, both SRI-compounds displayed a similar decrease (30%) in IC50for inhibition of [3H]DA uptake by cocaine in WT hDAT. The addition of SRI-20041 or SRI-30827 following cocaine slowed the dissociation rate of [3H]WIN35,428 binding in WT hDAT relative to cocaine alone. Moreover, Y470H and Y88F hDAT potentiate the inhibitory effect of cocaine on DA uptake and attenuate the effects of SRI-compounds on cocaine-mediated dissociation rate. SRI-30827 attenuated Tat-induced inhibition of [3H]WIN35,428 binding. These observations demonstrate that tyrosine 470 and 88 are critical for allosteric modulatory effects of SRI-compounds on the interaction of cocaine with hDAT.
Interaction of the Antimicrobial Peptide Aurein 1.2 and Charged Lipid Bilayer
Authors: Rai Durgesh K. , Qian Shuo 
Published: June 2017

AbstractAurein 1.2 is a potent antimicrobial peptide secreted by frog Litoria aurea. As a short membrane-active peptide with only 13 amino acids in sequence, it has been found to be residing on the surface of lipid bilayer and permeabilizing bacterial membranes at high concentration. However, the detail at the molecular level is largely unknown. In this study, we investigated the action of Aurein 1.2 in charged lipid bilayers composed of DMPC/DMPG. Oriented Circular Dichroism results showed that the peptide was on the surface of lipid bilayer regardless of the charged lipid ratio. Only at a very high peptide-to-lipid ratio (~1/10), the peptide became perpendicular to the bilayer, however no pore was detected by neutron in-plane scattering. To further understand how it interacted with charged lipid bilayers, we employed Small Angle Neutron Scattering to probe lipid distribution across bilayer leaflets in lipid vesicles. The results showed that Aurein 1.2 interacted strongly with negatively charged DMPG, causing strong asymmetry in lipid bilayer. At high concentration, while the vesicles were intact, we found additional structure feature on the bilayer. Our study provides a glimpse into how Aurein 1.2 disturbs anionic lipid-containing membranes without pore formation.