bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partial Reprogramming of Pluripotent Stem Cell-Derived Cardiomyocytes into Neurons
Authors: Chuang Wenpo , Sharma Arun , Shukla Praveen , Li Guang , Mall Moritz , Rajarajan Kuppusamy , Abilez Oscar J. , Hamaguchi Ryoko , Wu Joseph C. , Wernig Marius , Wu Sean M. 
Published: March 2017

AbstractDirect reprogramming of somatic cells has been demonstrated, however, it is unknown whether electrophysiologically-active somatic cells derived from separate germ layers can be interconverted. We demonstrate that partial direct reprogramming of mesoderm-derived cardiomyocytes into neurons is feasible, generating cells exhibiting structural and electrophysiological properties of both cardiomyocytes and neurons. Human and mouse pluripotent stem cell-derived CMs (PSC-CMs) were transduced with the neurogenic transcription factors Brn2, Ascl1, Myt1l and NeuroD. We found that CMs adopted neuronal morphologies as early as day 3 post-transduction while still retaining a CM gene expression profile. At week 1 post-transduction, we found that reprogrammed CMs expressed neuronal markers such as Tuj1, Map2, and NCAM. At week 3 post-transduction, mature neuronal markers such as vGlut and synapsin were observed. With single-cell qPCR, we temporally examined CM gene expression and observed increased expression of neuronal markers Dcx, Map2, and Tubb3. Patch-clamp analysis confirmed the neuron-like electrophysiological profile of reprogrammed CMs. This study demonstrates that PSC-CMs are amenable to partial neuronal conversion, yielding a population of cells exhibiting features of both neurons and CMs.
Non-occupational physical activity during pregnancy and the risk of preterm birth: a meta-analysis of observational and interventional studies
Authors: Wen Ju , Xun Pengcheng , Chen Cheng , Quan Minghui , Wang Ru , Liu Yu , He Ka 
Published: March 2017

AbstractA meta-analysis was conducted to evaluate the association between non-occupational physical activity (PA) during pregnancy and the risk of preterm birth (PTB). By searching PubMed and EMBASE from inception to August 20, 2016, 25 observational studies (18 cohorts and 7 case-controls) and 12 interventional studies were identified. Comparing the highest to the lowest category of leisure-time PA during pregnancy, the pooled relative risk (RR) of PTB was 0.83 [95% confidence interval (CI) = 0.74–0.93] for cohort studies and 0.60 (95% CI = 0.43–0.84) for case-control studies. No overall significant association was found between domestic or commuting PA and the risk of PTB. In addition, PA intervention did not indicate significant beneficial effect on the risk of PTB. Evidence from the observational studies suggested that leisure-time, but not domestic or commuting, PA during pregnancy was inversely associated with the risk of PTB. The findings were not supported by small-scale and short-term interventional studies. Further research with objective measurement on leisure-time PA is warranted.
Synthesis of Norbornene Derived Helical Copolymer by Simple Molecular Marriage Approach to Produce Smart Nanocarrier
Authors: Mane Shivshankar R. , Sathyan Ashlin , Shunmugam Raja 
Published: March 2017

AbstractA novel library of norbornene derived helical copolymer has been synthesized through the coupling of two homopolymers via Molecular Marriage Approach. The helicity is governed by the non-covalent interactions like hydrogen bonding, π-π stacking and the influence of hydrophobic and hydrophilic motifs. The detailed characterization of the copolymer (Copoly 1) has been provided and the super structures are confirmed through dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The observed size of the aggregates was about 200 nm. The density functional theory (DFT) is favorably supported for the formation of proposed structure of Copoly 1. Circular dichroism (CD) measurement has confirmed the one handed helical structure of the copolymer. Reservoir capability of this pH responsive polymer (Copoly 1) to encapsulate anti-cancer drug doxorubicin (DOX) warrants its potential applications in the field of bio-medical sciences.
Elaboration and controlling excited state double proton transfer mechanism of 2,5-bis(benzoxazol-2-yl)thiophene-3,4-diol
Authors: Zhao Jinfeng , Zheng Yujun 
Published: March 2017

AbstractIn the present work, we theoretically illuminate the excited state double proton transfer (ESDPT) process about a novel synthesized system 2,5-bis(benzoxazol-2-yl)thiophene-3,4-diol (BBTD). Minor changes of both structure and charge redistribution deriving from photoexcitation result in obviously different excited state dynamical process. Exploration about our constructed S1-state potential energy surface (PES) indicates a stepwise ESDPT mechanism for BBTD. In addition, we present a new mechanism about regulating and controlling stepwise ESDPT process via external electric field.
Pollen-mediated gene flow from glyphosate-resistant common waterhemp (Amaranthus rudis Sauer): consequences for the dispersal of resistance genes
Authors: Sarangi Debalin , Tyre Andrew J. , Patterson Eric L. , Gaines Todd A. , Irmak Suat , Knezevic Stevan Z. , Lindquist John L. , Jhala Amit J. 
Published: March 2017

AbstractGene flow is an important component in evolutionary biology; however, the role of gene flow in dispersal of herbicide-resistant alleles among weed populations is poorly understood. Field experiments were conducted at the University of Nebraska-Lincoln to quantify pollen-mediated gene flow (PMGF) from glyphosate-resistant (GR) to -susceptible (GS) common waterhemp using a concentric donor-receptor design. More than 130,000 common waterhemp plants were screened and 26,199 plants were confirmed resistant to glyphosate. Frequency of gene flow from all distances, directions, and years was estimated with a double exponential decay model using Generalized Nonlinear Model (packagegnm) in R. PMGF declined by 50% at <3 m distance from the pollen source, whereas 90% reduction was found at 88 m (maximum) depending on the direction of the pollen-receptor blocks. Amplification of the target site gene, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), was identified as the mechanism of glyphosate resistance in parent biotype. TheEPSPSgene amplification was heritable in common waterhemp and can be transferred via PMGF, and also correlated with glyphosate resistance in pseudo-F2progeny. This is the first report of PMGF in GR common waterhemp and the results are critical in explaining the rapid dispersal of GR common waterhemp in Midwestern United States.
Global DNA Methylation Analysis Identifies Two Discrete clusters of Pheochromocytoma with Distinct Genomic and Genetic Alterations
Authors: Backman Samuel , Maharjan Rajani , Falk-Delgado Alberto , Crona Joakim , Cupisti Kenko , Stålberg Peter , Hellman Per , Björklund Peyman 
Published: March 2017

AbstractPheochromocytomas and paragangliomas (PPGLs) are rare and frequently heritable neural-crest derived tumours arising from the adrenal medulla or extra-adrenal chromaffin cells respectively. The majority of PPGL tumours are benign and do not recur with distant metastases. However, a sizeable fraction of these tumours secrete vasoactive catecholamines into the circulation causing a variety of symptoms including hypertension, palpitations and diaphoresis. The genetic landscape of PPGL has been well characterized and more than a dozen genes have been described as recurrently mutated. Recent studies of DNA-methylation have revealed distinct clusters of PPGL that share DNA methylation patterns and driver mutations, as well as identified potential biomarkers for malignancy. However, these findings have not been adequately validated in independent cohorts. In this study we use an array-based genome-wide approach to study the methylome of 39 PPGL and 4 normal adrenal medullae. We identified two distinct clusters of tumours characterized by different methylation patterns and different driver mutations. Moreover, we identify genes that are differentially methylated between tumour subcategories, and between tumours and normal tissue.
Conditional deletion of Ndufs4 in dopaminergic neurons promotes Parkinson’s disease-like non-motor symptoms without loss of dopamine neurons
Authors: Choi Won-Seok , Kim Hyung-Wook , Tronche François , Palmiter Richard D. , Storm Daniel R. , Xia Zhengui 
Published: March 2017

AbstractReduction of mitochondrial complex I activity is one of the major hypotheses for dopaminergic neuron death in Parkinson’s disease. However, reduction of complex I activity in all cells or selectively in dopaminergic neurons via conditional deletion of theNdufs4gene, a subunit of the mitochondrial complex I, does not cause dopaminergic neuron death or motor impairment. Here, we investigated the effect of reduced complex I activity on non-motor symptoms associated with Parkinson’s disease using conditional knockout (cKO) mice in whichNdufs4was selectively deleted in dopaminergic neurons (Ndufs4cKO). This conditional deletion ofNdufs4,which reduces complex I activity in dopamine neurons, did not cause a significant loss of dopaminergic neurons in substantia nigra pars compacta (SNpc), and there was no loss of dopaminergic neurites in striatum or amygdala. However,Ndufs4cKO mice had a reduced amount of dopamine in the brain compared to control mice. Furthermore, even though motor behavior were not affected,Ndufs4cKO mice showed non-motor symptoms experienced by many Parkinson’s disease patients including impaired cognitive function and increased anxiety-like behavior. These data suggest that mitochondrial complex I dysfunction in dopaminergic neurons promotes non-motor symptoms of Parkinson’s disease and reduces dopamine content in the absence of dopamine neuron loss.
Estimated Daily Intake and Cumulative Risk Assessment of Phthalates in the General Taiwanese after the 2011 DEHP Food Scandal
Authors: Chang Jung-Wei , Lee Ching-Chang , Pan Wen-Harn , Chou Wei-Chun , Huang Han-Bin , Chiang Hung-Che , Huang Po-Chin 
Published: March 2017

AbstractA food scandal occurred in Taiwan in 2011 because the DEHP (di-2-ethylhexyl phthalate) had been intentionally used in food products. We assessed the daily intakes (DIs) and cumulative risk of phthalates in Taiwan’s general population after the scandal. The DIs of 6 phthalates, including di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), and DEHP, were evaluated using urinary phthalate metabolites. Hazard quotients of phthalates classified as affecting the reproductive (HQrep) and hepatic (HQhep) systems were assessed using cumulative approach. The creatinine-based model showed that the highest DI values in children 7-to 12- years-old were for DEHP (males: median: 4.79 μg/kg bw/d; females: median: 2.62 μg/kg bw/d). The 95th percentile (P95) of HQrep values were all >1 in the 7- to 12-year-old and 18- to 40-year-old male groups. The P95 of HQhep values were all >1 in the 7- to 18- year-old male groups. Most of the HQrep was attributable to the HQs of DnBP and DiBP (53.9–84.7%), and DEHP contributed most to HQhep (83.1–98.6%), which reveals that DnBP, DiBP and DEHP were the main risk of phthalate exposure for Taiwanese. Taiwan’s general population is widely exposed to DnBP, DiBP and DEHP, especially for young children.
Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system
Authors: Yoshimoto Yuki , Takimoto Aki , Watanabe Hitomi , Hiraki Yuji , Kondoh Gen , Shukunami Chisa 
Published: March 2017

AbstractScleraxis (Scx) is a basic helix-loop-helix transcription factor that is expressed persistently in tendons/ligaments, but transiently in entheseal cartilage. In this study, we generated a novel ScxCre knock-in (KI) allele, by in-frame replacement of most of Scx exon 1 with Cre recombinase (Cre), to drive Cre expression using Scx promoter and to inactivate the endogenous Scx. Reflecting the intensity and duration of endogenous expression, Cre-mediated excision occurs in tendinous and ligamentous tissues persistently expressing Scx. Expression of tenomodulin, a marker of mature tenocytes and ligamentocytes, was almost absent in tendons and ligaments of ScxCre/Cre KI mice lacking Scx to indicate defective maturation. In homozygotes, the transiently Scx-expressing entheseal regions such as the rib cage, patella cartilage, and calcaneus were small and defective and cartilaginous tuberosity was missing. Decreased Sox9 expression and phosphorylation of Smad1/5 and Smad3 were also observed in the developing entheseal cartilage, patella, and deltoid tuberosity of ScxCre/Cre KI mice. These results highlighted the functional importance of both transient and persistent expression domains of Scx for proper integration of the musculoskeletal components.
Dynasore impairs VEGFR2 signalling in an endocytosis-independent manner
Authors: Basagiannis Dimitris , Zografou Sofia , Galanopoulou Katerina , Christoforidis Savvas 
Published: March 2017

AbstractVEGFR2 is a critical angiogenic receptor playing a key role in vascular homeostasis. Upon activation by VEGF, VEGFR2 becomes endocytosed. Internalisation of VEGFR2 is facilitated, in part, through clathrin mediated endocytosis (CME), the role of which in VEGFR2 function is debated. Here, we confirm the contribution of CME in VEGFR2 uptake. However, curiously, we find that different approaches of inhibition of CME exert contradictory effects on VEGF signalling; knockdown of clathrin, or of dynamin, or overexpression of dynamin K44A, do not affect VEGF-induced phosphorylation of ERK1/2, while dynasore causes strong inhibition. We resolve this discrepancy by showing that although dynasore inhibits CME of VEGFR2, its inhibitory action in ERK1/2 phosphorylation is not related to attenuation of VEGFR2 endocytosis; it is rather due to an off-target effect of the drug. Dynasore inhibits VEGF-induced calcium release, a signalling event that lies upstream of ERK1/2, which implies that this effect could be responsible, at least in part, for the inhibitory action of the drug on VEGF-to-ERK1/2 signalling. These results raise caution that although dynasore is specific in inhibiting clathrin- and dynamin-mediated endocytosis, it may also exert off-target effects on signalling molecules, hence influencing the interpretation of the role of endocytosis in signalling.
Tandem UIMs confer Lys48 ubiquitin chain substrate preference to deubiquitinase USP25
Authors: Kawaguchi Kohei , Uo Kazune , Tanaka Toshiaki , Komada Masayuki 
Published: March 2017

AbstractUbiquitin-specific protease (USP) 25, belonging to the USP family of deubiquitinases, harbors two tandem ubiquitin-interacting motifs (UIMs), a ~20-amino-acid α-helical stretch that binds to ubiquitin. However, the role of the UIMs in USP25 remains unclear. Here we show that the tandem UIM region binds to Lys48-, but not Lys63-, linked ubiquitin chains, where the two UIMs played a critical and cooperative role. Purified USP25 exhibited higher ubiquitin isopeptidase activity to Lys48-, than to Lys63-, linked ubiquitin chains. Mutations that disrupted the ubiquitin-binding ability of the tandem UIMs resulted in a reduced ubiquitin isopeptidase activity of USP25, suggesting a role for the UIMs in exerting the full catalytic activity of USP25. Moreover, when mutations that convert the binding preference from Lys48- to Lys63-linked ubiquitin chains were introduced into the tandem UIM region, the USP25 mutants acquired elevated and reduced isopeptidase activity toward Lys63- and Lys48-linked ubiquitin chains, respectively. These results suggested that the binding preference of the tandem UIMs toward Lys48-linked ubiquitin chains contributes not only to the full catalytic activity but also to the ubiquitin chain substrate preference of USP25, possibly by selectively holding the Lys48-linked ubiquitin chain substrates in the proximity of the catalytic core.
Anisotropy of hydrogen diffusion in nickel single crystals: the effects of self-stress and hydrogen concentration on diffusion
Authors: Li J. , Oudriss A. , Metsue A. , Bouhattate J. , Feaugas X. 
Published: March 2017

AbstractHydrogen diffusion has an important role in solute-dependent hydrogen embrittlement in metals and metallic alloys. In spite of extensive studies, the complexity of hydrogen diffusion in solids remains a phenomenon that needs to be clarified. In this paper, we investigate the anisotropy of hydrogen diffusion in pure nickel single crystals using both an experimental approach and a thermodynamic development. As a first approximation, experimental data from electrochemical permeation and thermal desorption spectroscopy are described using the classical Fick’s laws and an apparent diffusion tensor. Within a thermodynamic framework, the diffusion equation can be derived from Fick’s laws with an apparent diffusion coefficient which contains an added solute content dependent term β. This term is due to the elastic strain field associated with the insertion of solute atoms. For nickel crystals, the dependence of β on the crystallographic orientation arises from the elastic anisotropy. Additionally, our results elucidate the discrepancies between the thermodynamic model and experimental observations of the effect of the solute concentration on the diffusion process. Moreover, this highlights the importance of the impact of hydrogen on vacancy formation and the subsequent consequences on the anisotropy of the apparent diffusion coefficient.
Correlation between Ultrasound Elastography and Histologic Characteristics of Papillary Thyroid Carcinoma
Authors: Yi Li , Qiong Wu , Yan Wang , Youben Fan , Bing Hu 
Published: March 2017

AbstractThe aim of this study was to investigate the correlation between elastography and histologic characteristics including fibrosis and calcification. We also wanted to investigate whether other clinicopathologic indexes influence the strain ratio (SR) of papillary thyroid carcinomas (PTCs). We retrospectively reviewed 126 papillary thyroid carcinomas (PTCs) from 103 patients who underwent ultrasonography and elastography before surgery. The histologic characteristics and clinicopathologic indexes were compared with the SR of ultrasound elastography (UE). The results showed that there was a significantly positive correlation between fibrosis degree and SR measurements (r = 0.754, p = 0.000); the SR was significantly different between the groups with and without calcification (11.34 ± 10.08 vs. 6.81 ± 7.33, p = 0.000). The standard coefficients of collagen and stromal calcification were 0.684 and 0.194, respectively. There was no significant correlation between SR and indices such as size, position, co-existence with Hashimoto’s thyroiditis (HT), multifocality or cervical lymph node (CLN) metastasis. In conclusion, we found that the SR of UE is positively correlated with the fibrosis of PTC. Stromal calcification will elevate the SR dramatically, but psammoma bodies will not when they exist in the absence of stromal calcification.
Molecular signaling underlying bulleyaconitine A (BAA)-induced microglial expression of prodynorphin
Authors: Li Teng-Fei , Wu Hai-Yun , Wang Yi-Rui , Li Xin-Yan , Wang Yong-Xiang 
Published: March 2017

AbstractBulleyaconitine (BAA) has been shown to possess antinociceptive activities by stimulation of dynorphin A release from spinal microglia. This study investigated its underlying signal transduction mechanisms. The data showed that (1) BAA treatment induced phosphorylation of CREB (rather than NF-κB) and prodynorphin expression in cultured primary microglia, and antiallodynia in neuropathy, which were totally inhibited by the CREB inhibitor KG-501; (2) BAA upregulated phosphorylation of p38 (but not ERK or JNK), and the p38 inhibitor SB203580 (but not ERK or JNK inhibitor) and p38β gene silencer siRNA/p38β (but not siRNA/p38α) completely blocked BAA-induced p38 phosphorylation and/or prodynorphin expression, and antiallodynia; (3) BAA stimulated cAMP production and PKA phosphorylation, and the adenylate cyclase inhibitor DDA and PKA inhibitor H-89 entirely antagonized BAA-induced prodynorphin expression and antiallodynia; (4) The Gs-protein inhibitor NF449 completely inhibited BAA-increased cAMP level, prodynorphin expression and antiallodynia, whereas the antagonists of noradrenergic, corticotrophin-releasing factor, A1 adenosine, formyl peptide, D1/D2 dopamine, and glucagon like-peptide-1 receptors failed to block BAA-induced antiallodynia. The data indicate that BAA-induced microglial expression of prodynorphin is mediated by activation of the cAMP-PKA-p38β-CREB signaling pathway, suggesting that its possible target is a Gs-protein-coupled receptor – “aconitine receptor”, although the chemical identity is not illustrated.
Significant Role of Collagen XVII And Integrin β4 in Migration and Invasion of The Less Aggressive Squamous Cell Carcinoma Cells
Authors: Moilanen Jyri M. , Löffek Stefanie , Kokkonen Nina , Salo Sirpa , Väyrynen Juha P. , Hurskainen Tiina , Manninen Aki , Riihilä Pilvi , Heljasvaara Ritva , Franzke Claus-Werner , Kähäri Veli-Matti , Salo Tuula , Mäkinen Markus J. , Tasanen Kaisa 
Published: March 2017

AbstractCollagen XVII and integrin α6β4 have well-established roles as epithelial adhesion molecules. Their binding partner laminin 332 as well as integrin α6β4 are largely recognized to promote invasion and metastasis in various cancers, and collagen XVII is essential for the survival of colon and lung cancer stem cells. We have studied the expression of laminin γ2, collagen XVII and integrin β4 in tissue microarray samples of squamous cell carcinoma (SCC) and its precursors, actinic keratosis and Bowen’s disease. The expression of laminin γ2 was highest in SCC samples, whereas the expression of collagen XVII and integrin β4 varied greatly in SCC and its precursors. Collagen XVII and integrin β4 were also expressed in SCC cell lines. Virus-mediated RNAi knockdown of collagen XVII and integrin β4 reduced the migration of less aggressive SCC-25 cells in horizontal scratch wound healing assay. Additionally, in a 3D organotypic myoma invasion assay the loss of collagen XVII or integrin β4 suppressed equally the migration and invasion of SCC-25 cells whereas there was no effect on the most aggressive HSC-3 cells. Variable expression patterns and results in migration and invasion assays suggest that collagen XVII and integrin β4 contribute to SCC tumorigenesis.
Transition of Temporal Scaling Behavior in Percolation Assisted Shear-branching Structure during Plastic Deformation
Authors: Ren Jingli , Chen Cun , Wang Gang , Liaw Peter K. 
Published: March 2017

AbstractThis paper explores the temporal scaling behavior induced shear-branching structure in response to variant temperatures and strain rates during plastic deformation of Zr-based bulk metallic glass (BMG). The data analysis based on the compression tests suggests that there are two states of shear-branching structures: the fractal structure with a long-range order at an intermediate temperature of 223 K and a larger strain rate of 2.5 × 10−2 s−1; the disordered structure dominated at other temperature and strain rate. It can be deduced from the percolation theory that the compressive ductility, ec, can reach the maximum value at the intermediate temperature. Furthermore, a dynamical model involving temperature is given for depicting the shear-sliding process, reflecting the plastic deformation has fractal structure at the temperature of 223 K and strain rate of 2.5 × 10−2 s−1.