bluuebunny/crossref_metadata_2025_split huggingface dataset:
Madelung and Hubbard interactions in polaron band model of doped organic semiconductors
Authors: Png Rui-Qi , Ang Mervin C.Y. , Teo Meng-How , Choo Kim-Kian , Tang Cindy Guanyu , Belaineh Dagmawi , Chua Lay-Lay , Ho Peter K.H. 
Published: September 2016

AbstractThe standard polaron band model of doped organic semiconductors predicts that density-of-states shift into the π–π* gap to give a partially filled polaron band that pins the Fermi level. This picture neglects both Madelung and Hubbard interactions. Here we show using ultrahigh workfunction hole-doped model triarylamine–fluorene copolymers that Hubbard interaction strongly splits the singly-occupied molecular orbital from its empty counterpart, while Madelung (Coulomb) interactions with counter-anions and other carriers markedly shift energies of the frontier orbitals. These interactions lower the singly-occupied molecular orbital band below the valence band edge and give rise to an empty low-lying counterpart band. The Fermi level, and hence workfunction, is determined by conjunction of the bottom edge of this empty band and the top edge of the valence band. Calculations are consistent with the observed Fermi-level downshift with counter-anion size and the observed dependence of workfunction on doping level in the strongly doped regime.
Virus-derived DNA drives mosquito vector tolerance to arboviral infection
Authors: Goic Bertsy , Stapleford Kenneth A. , Frangeul Lionel , Doucet Aurélien J. , Gausson Valérie , Blanc Hervé , Schemmel-Jofre Nidia , Cristofari Gael , Lambrechts Louis , Vignuzzi Marco , Saleh Maria-Carla 
Published: September 2016

AbstractMosquitoes develop long-lasting viral infections without substantial deleterious effects, despite high viral loads. This makes mosquitoes efficient vectors for emerging viral diseases with enormous burden on public health. How mosquitoes resist and/or tolerate these viruses is poorly understood. Here we show that two species of Aedes mosquitoes infected with two arboviruses from distinct families (dengue or chikungunya) generate a viral-derived DNA (vDNA) that is essential for mosquito survival and viral tolerance. Inhibition of vDNA formation leads to extreme susceptibility to viral infections, reduction of viral small RNAs due to an impaired immune response, and loss of viral tolerance. Our results highlight an essential role of vDNA in viral tolerance that allows mosquito survival and thus may be important for arbovirus dissemination and transmission. Elucidating the mechanisms of mosquito tolerance to arbovirus infection paves the way to conceptualize new antivectorial strategies to selectively eliminate arbovirus-infected mosquitoes.
The myosin X motor is optimized for movement on actin bundles
Authors: Ropars Virginie , Yang Zhaohui , Isabet Tatiana , Blanc Florian , Zhou Kaifeng , Lin Tianming , Liu Xiaoyan , Hissier Pascale , Samazan Frédéric , Amigues Béatrice , Yang Eric D. , Park Hyokeun , Pylypenko Olena , Cecchini Marco , Sindelar Charles V. , Sweeney H. Lee , Houdusse Anne 
Published: September 2016

AbstractMyosin X has features not found in other myosins. Its structure must underlie its unique ability to generate filopodia, which are essential for neuritogenesis, wound healing, cancer metastasis and some pathogenic infections. By determining high-resolution structures of key components of this motor, and characterizing the in vitro behaviour of the native dimer, we identify the features that explain the myosin X dimer behaviour. Single-molecule studies demonstrate that a native myosin X dimer moves on actin bundles with higher velocities and takes larger steps than on single actin filaments. The largest steps on actin bundles are larger than previously reported for artificially dimerized myosin X constructs or any other myosin. Our model and kinetic data explain why these large steps and high velocities can only occur on bundled filaments. Thus, myosin X functions as an antiparallel dimer in cells with a unique geometry optimized for movement on actin bundles.
Transition to and from the skyrmion lattice phase by electric fields in a magnetoelectric compound
Authors: Okamura Y. , Kagawa F. , Seki S. , Tokura Y. 
Published: September 2016

AbstractDissipation-less electric control of magnetic state variable is an important target of contemporary spintronics. The non-volatile control of magnetic skyrmions, nanometre-sized spin-swirling objects, with electric fields may exemplify this goal. The skyrmion-hosting magnetoelectric chiral magnet Cu2OSeO3 provides a unique platform for the implementation of such control; however, the hysteresis that accompanies the first-order transition associated with the skyrmion phase is negligibly narrow in practice. Here we demonstrate another method that functions irrespective of the transition boundary. Combination of magnetic-susceptibility measurements and microwave spectroscopy reveals that although the metastable skyrmion lattice is normally hidden behind a more thermodynamically stable conical phase, it emerges under electric fields and persists down to the lowest temperature. Once created, this metastable skyrmion lattice remains without electric fields, establishing a bistability distinct from the transition hysteresis. This bistability thus enables non-volatile electric-field control of the skyrmion lattice even in temperature/magnetic-field regions far from the transition boundary.
ORP4L is essential for T-cell acute lymphoblastic leukemia cell survival
Authors: Zhong Wenbin , Yi Qing , Xu Bing , Li Shiqian , Wang Tong , Liu Fupei , Zhu Biying , Hoffmann Peter R. , Ji Guangju , Lei Pingsheng , Li Guoping , Li Jiwei , Li Jian , Olkkonen Vesa M. , Yan Daoguang 
Published: September 2016

AbstractMetabolic pathways are reprogrammed in cancer to support cell survival. Here, we report that T-cell acute lymphoblastic leukemia (T-ALL) cells are characterized by increased oxidative phosphorylation and robust ATP production. We demonstrate that ORP4L is expressed in T-ALL but not normal T-cells and its abundance is proportional to cellular ATP. ORP4L acts as an adaptor/scaffold assembling CD3ɛ, Gαq/11 and PLCβ3 into a complex that activates PLCβ3. PLCβ3 catalyzes IP3 production in T-ALL as opposed to PLCγ1 in normal T-cells. Up-regulation of ORP4L thus results in a switch in the enzyme responsible for IP3-induced endoplasmic reticulum Ca2+ release and oxidative phosphorylation. ORP4L knockdown results in suboptimal bioenergetics, cell death and abrogation of T-ALL engraftment in vivo. In summary, we uncovered a signalling pathway operating specifically in T-ALL cells in which ORP4L mediates G protein-coupled ligand-induced PLCβ3 activation, resulting in an increase of mitochondrial respiration for cell survival. Targeting ORP4L might represent a promising approach for T-ALL treatment.
Strong cooperative coupling of pressure-induced magnetic order and nematicity in FeSe
Authors: Kothapalli K. , Böhmer A. E. , Jayasekara W. T. , Ueland B. G. , Das P. , Sapkota A. , Taufour V. , Xiao Y. , Alp E. , Bud’ko S. L. , Canfield P. C. , Kreyssig A. , Goldman A. I. 
Published: September 2016

AbstractA hallmark of the iron-based superconductors is the strong coupling between magnetic, structural and electronic degrees of freedom. However, a universal picture of the normal state properties of these compounds has been confounded by recent investigations of FeSe where the nematic (structural) and magnetic transitions appear to be decoupled. Here, using synchrotron-based high-energy x-ray diffraction and time-domain Mössbauer spectroscopy, we show that nematicity and magnetism in FeSe under applied pressure are indeed strongly coupled. Distinct structural and magnetic transitions are observed for pressures between 1.0 and 1.7 GPa and merge into a single first-order transition for pressures ≳1.7 GPa, reminiscent of what has been found for the evolution of these transitions in the prototypical system Ba(Fe1−xCox)2As2. Our results are consistent with a spin-driven mechanism for nematic order in FeSe and provide an important step towards a universal description of the normal state properties of the iron-based superconductors.
ge-CRISPR - An integrated pipeline for the prediction and analysis of sgRNAs genome editing efficiency for CRISPR/Cas system
Authors: Kaur Karambir , Gupta Amit Kumar , Rajput Akanksha , Kumar Manoj 
Published: September 2016

AbstractGenome editing by sgRNA a component of CRISPR/Cas system emerged as a preferred technology for genome editing in recent years. However, activity and stability of sgRNA in genome targeting is greatly influenced by its sequence features. In this endeavor, a few prediction tools have been developed to design effective sgRNAs but these methods have their own limitations. Therefore, we have developed “ge-CRISPR” using high throughput data for the prediction and analysis of sgRNAs genome editing efficiency. Predictive models were employed using SVM for developing pipeline-1 (classification) and pipeline-2 (regression) using 2090 and 4139 experimentally verified sgRNAs respectively from Homo sapiens, Mus musculus, Danio rerio and Xenopus tropicalis. During 10-fold cross validation we have achieved accuracy and Matthew’s correlation coefficient of 87.70% and 0.75 for pipeline-1 on training dataset (T1840) while it performed equally well on independent dataset (V250). In pipeline-2 we attained Pearson correlation coefficient of 0.68 and 0.69 using best models on training (T3169) and independent dataset (V520) correspondingly. ge-CRISPR (http://bioinfo.imtech.res.in/manojk/gecrispr/) for a given genomic region will identify potent sgRNAs, their qualitative as well as quantitative efficiencies along with potential off-targets. It will be useful to scientific community engaged in CRISPR research and therapeutics development.
Liraglutide prevents and reverses monocrotaline-induced pulmonary arterial hypertension by suppressing ET-1 and enhancing eNOS/sGC/PKG pathways
Authors: Lee Mei-Yueh , Tsai Kun-Bow , Hsu Jong-Hau , Shin Shyi-Jang , Wu Jiunn-Ren , Yeh Jwu-Lai 
Published: September 2016

AbstractLiraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is widely used to treat diabetes. However, its effect on pulmonary arterial hypertension (PAH) is unknown. In this study, we investigated its effects on rats with monocrotaline (MCT)-induced PAH and mechanisms on rat pulmonary artery smooth muscle cells (PASMCs). Liraglutide was investigated for both prevention and treatment of MCT-induced PAH. The hemodynamic and body weight changes, right heart hypertrophy, lung morphology, immune-reactivity of endothelial nitric oxide synthase (eNOS), endothelin-1 and cyclic guanosine monophosphate (cGMP) levels, protein expressions of eNOS, soluble guanylyl cyclase (sGCα), protein kinase G (PKG) and Rho kinase (ROCK) II pathway were measured in both in vivo and in vitro. Cell migration and cell cycle were also determined. Liraglutide both prevented and reversed MCT-induced PAH, right ventricle hypertrophy and pulmonary vascular wall remodeling. Protein expression of ROCK II was increased while eNOS, sGC and PKG were decreased. Pretreatment with liraglutide inhibited platelet-derived growth factor (PDGF)-BB stimulated PASMCs migration, which were associated with cell-cycle arrest at G0/G1 phase. Liraglutide may have both preventive and therapeutic effects on MCT-induced PAH, through the eNOS/sGC/PKG and Rho kinase pathways. Thus, liraglutide may have a therapeutic role in pulmonary vascular remodelling.
Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models
Authors: Shen Xiujin , Jiang Hong , Ying Meike , Xie Zhoutao , Li Xiayu , Wang Haibing , Zhao Jie , Lin Chuan , Wang Yucheng , Feng Shi , Shen Jia , Weng Chunhua , Lin Weiqiang , Wang Huiping , Zhou Qin , Bi Yan , Li Meng , Wang Lingyan , Zhu Tongyu , Huang Xiaoru , Lan Hui-Yao , Zhou Jing , Chen Jianghua 
Published: September 2016

AbstractPodocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway.
Time-resolved, single-cell analysis of induced and programmed cell death via non-invasive propidium iodide and counterstain perfusion
Authors: Krämer Christina E. M. , Wiechert Wolfgang , Kohlheyer Dietrich 
Published: September 2016

AbstractConventional propidium iodide (PI) staining requires the execution of multiple steps prior to analysis, potentially affecting assay results as well as cell vitality. In this study, this multistep analysis method has been transformed into a single-step, non-toxic, real-time method via live-cell imaging during perfusion with 0.1 μM PI inside a microfluidic cultivation device. Dynamic PI staining was an effective live/dead analytical tool and demonstrated consistent results for single-cell death initiated by direct or indirect triggers. Application of this method for the first time revealed the apparent antibiotic tolerance of wild-typeCorynebacterium glutamicumcells, as indicated by the conversion of violet fluorogenic calcein acetoxymethyl ester (CvAM). Additional implementation of this method provided insight into the induced cell lysis ofEscherichia colicells expressing a lytic toxin-antitoxin module, providing evidence for non-lytic cell death and cell resistance to toxin production. Finally, our dynamic PI staining method distinguished necrotic-like and apoptotic-like cell death phenotypes inSaccharomyces cerevisiaeamong predisposed descendants of nutrient-deprived ancestor cells using PO-PRO-1 or green fluorogenic calcein acetoxymethyl ester (CgAM) as counterstains. The combination of single-cell cultivation, fluorescent time-lapse imaging and PI perfusion facilitates spatiotemporally resolved observations that deliver new insights into the dynamics of cellular behaviour.
The efficacy and safety of proton-pump inhibitors in treating patients with non-erosive reflux disease: a network meta-analysis
Authors: Chen Lingxiao , Chen Yujie , Li Bo 
Published: September 2016

AbstractProton-pump inhibitors (PPIs) have been proved as safe and effective ways to treat patients with non-erosive reflux disease (NERD). However, less is known about the comparisons among different PPIs and their best dosage. We aimed to synthesize the available evidence through network meta-analysis to investigate the efficacy and safety of different PPIs in treating patients with NERD. Fifteen studies with 6309 patients were included in the meta-analyses. For the rate of symptomatic relief, compared with control groups, all interventions except rabeprazole 5 mg significantly increased rate of symptomatic relief. Among the comparisons of different interventions, omeprazole 20 mg group was associated with a higher rate of symptomatic relief in contrast to omeprazole 10 mg group (odds ratio, OR: 1.89, 95% confidence interval, CI: 1.34, 2.67; p-value: 0.0005) or rabeprazole 5 mg group (OR: 2.51, 95%CI: 1.16, 5.42; p-value: 0.019); dexlansoprazole 30 mg therapy significantly improved the rate of symptomatic relief compared with rabeprazole 5 mg group (OR: 2.64, 95%CI: 1.08, 6.43; p-value: 0.03). For the rate of adverse events, there was no significant difference among all interventions.
Glucagon regulates hepatic lipid metabolism via cAMP and Insig-2 signaling: implication for the pathogenesis of hypertriglyceridemia and hepatic steatosis
Authors: Wang Hai , Zhao Miaoyun , Sud Neetu , Christian Patricia , Shen Jing , Song Yongyan , Pashaj Anjeza , Zhang Kezhong , Carr Timothy , Su Qiaozhu 
Published: September 2016

AbstractInsulin induced gene-2 (Insig-2) is an ER-resident protein that inhibits the activation of sterol regulatory element-binding proteins (SREBPs). However, cellular factors that regulate Insig-2 expression have not yet been identified. Here we reported that cyclic AMP-responsive element-binding protein H (CREBH) positively regulates mRNA and protein expression of a liver specific isoform of Insig-2, Insig-2a, which in turn hinders SREBP-1c activation and inhibits hepatic de novo lipogenesis. CREBH binds to the evolutionally conserved CRE-BP binding elements located in the enhancer region of Insig-2a and upregulates its mRNA and protein expression. Metabolic hormone glucagon and nutritional fasting activated CREBH, which upregulated expression of Insig-2a in hepatocytes and inhibited SREBP-1c activation. In contrast, genetic depletion of CREBH decreased Insig-2a expression, leading to the activation of SREBP-1c and its downstream lipogenic target enzymes. Compromising CREBH-Insig-2 signaling by siRNA interference against Insig-2 also disrupted the inhibitory effect of this signaling pathway on hepatic de novo triglyceride synthesis. These actions resulted in the accumulation of lipid droplets in hepatocytes and systemic hyperlipidemia. Our study identified CREBH as the first cellular protein that regulates Insig-2a expression. Glucagon activated the CREBH-Insig-2a signaling pathway to inhibit hepatic de novo lipogenesis and prevent the onset of hepatic steatosis and hypertriglyceridemia.
Single Molecule Fluorescence Microscopy and Machine Learning for Rhesus D Antigen Classification
Authors: Borgmann Daniela M. , Mayr Sandra , Polin Helene , Schaller Susanne , Dorfer Viktoria , Obritzberger Lisa , Endmayr Tanja , Gabriel Christian , Winkler Stephan M. , Jacak Jaroslaw 
Published: September 2016

AbstractIn transfusion medicine, the identification of the Rhesus D type is important to prevent anti-D immunisation in Rhesus D negative recipients. In particular, the detection of the very low expressed DEL phenotype is crucial and hence constitutes the bottleneck of standard immunohaematology. The current method of choice, adsorption-elution, does not provide unambiguous results. We have developed a complementary method of high sensitivity that allows reliable identification of D antigen expression. Here, we present a workflow composed of high-resolution fluorescence microscopy, image processing, and machine learning that - for the first time - enables the identification of even small amounts of D antigen on the cellular level. The high sensitivity of our technique captures the full range of D antigen expression (including D+, weak D, DEL, D−), allows automated population analyses, and results in classification test accuracies of up to 96%, even for very low expressed phenotypes.
Stimulatory effects of the degradation products from Mg-Ca-Sr alloy on the osteogenesis through regulating ERK signaling pathway
Authors: Li Mei , He Peng , Wu Yuanhao , Zhang Yu , Xia Hong , Zheng Yufeng , Han Yong 
Published: September 2016

AbstractThe influence of Mg-1Ca-xwt.% Sr (x = 0.2, 0.5, 1.0, 2.0) alloys on the osteogenic differentiation and mineralization of pre-osteoblast MC3T3-E1 were studied through typical differentiation markers, such as intracellular alkaline phosphatase (ALP) activity, extracellular collagen secretion and calcium nodule formation. It was shown that Mg-1Ca alloys with different content of Sr promoted cell viability and enhanced the differentiation and mineralization levels of osteoblasts and Mg-1Ca-2.0Sr alloy had the most remarkable and significant effect among all. To further investigate the underlying mechanisms, RT-PCR and Western Blotting assays were taken to analyze the mRNA expression level of osteogenesis-related genes and intracellular signaling pathways involved in osteogenesis, respectively. RT-PCR results showed that Mg-1Ca-2.0Sr alloy significantly up-regulated the expressions of the transcription factors of Runt-related transcription factor 2 (RUNX2) and Osterix (OSX), Integrin subunits, as well as alkaline phosphatase (ALP), Bone sialoprotein (BSP), Collagen I (COL I), Osteocalcin (OCN) and Osteopontin (OPN). Western Blotting results suggested that Mg-1Ca-2.0Sr alloy rapidly induced extracellular signal-regulated kinase (ERK) activation but showed no obvious effects on c-Jun N terminal kinase (JNK) and p38 kinase of MAPK. Taken together, our results demonstrated that Mg-1Ca-2.0Sr alloy had excellent biocompatibility and osteogenesis via the ERK pathway and is expected to be promising as orthopedic implants and bone repair materials.
dRHP-PseRA: detecting remote homology proteins using profile-based pseudo protein sequence and rank aggregation
Authors: Chen Junjie , Long Ren , Wang Xiao-long , Liu Bin , Chou Kuo-Chen 
Published: September 2016

AbstractProtein remote homology detection is an important task in computational proteomics. Some computational methods have been proposed, which detect remote homology proteins based on different features and algorithms. As noted in previous studies, their predictive results are complementary to each other. Therefore, it is intriguing to explore whether these methods can be combined into one package so as to further enhance the performance power and application convenience. In view of this, we introduced a protein representation called profile-based pseudo protein sequence to extract the evolutionary information from the relevant profiles. Based on the concept of pseudo proteins, a new predictor, called “dRHP-PseRA”, was developed by combining four state-of-the-art predictors (PSI-BLAST, HHblits, Hmmer, and Coma) via the rank aggregation approach. Cross-validation tests on a SCOP benchmark dataset have demonstrated that the new predictor has remarkably outperformed any of the existing methods for the same purpose on ROC50 scores. Accordingly, it is anticipated that dRHP-PseRA holds very high potential to become a useful high throughput tool for detecting remote homology proteins. For the convenience of most experimental scientists, a web-server for dRHP-PseRA has been established at http://bioinformatics.hitsz.edu.cn/dRHP-PseRA/.
The onset of electrospray: the universal scaling laws of the first ejection
Authors: Gañán-Calvo A. M. , López-Herrera J. M. , Rebollo-Muñoz N. , Montanero J. M. 
Published: September 2016

AbstractThe disintegration of liquid drops with low electrical conductivity and subject to an electric field is investigated both theoretically and experimentally. This disintegration takes place through the development of a conical cusp that eventually ejects an ultrathin liquid ligament. A first tiny drop is emitted from the end of this ligament. Due to its exceptionally small size and large electric charge per unit volume, that drop has been the object of relevant recent studies. In this paper, universal scaling laws for the diameter and electric charge of the first issued droplet are proposed and validated both numerically and experimentally. Our analysis shows how charge relaxation is the mechanism that differentiates the onset of electrospray, including the first droplet ejection, from the classical steady cone-jet mode. In this way, our study identifies when and where charge relaxation and electrokinetic phenomena come into play in electrospray, a subject of live controversy in the field.