bluuebunny/crossref_metadata_2025_split huggingface dataset:
High light intensity plays a major role in emergence of population level variation in Arabidopsis thaliana along an altitudinal gradient
Authors: Tyagi Antariksh , Yadav Amrita , Tripathi Abhinandan Mani , Roy Sribash 
Published: May 2016

AbstractEnvironmental conditions play an important role in the emergence of genetic variations in natural populations. We identified genome-wide patterns of nucleotide variations in the coding regions of natural Arabidopsis thaliana populations. These populations originated from 700 m to 3400 m a.m.s.l. in the Western Himalaya. Using a pooled RNA-Seq approach, we identified the local and global level population-specific SNPs. The biological functions of the SNP-containing genes were primarily related to the high light intensity prevalent at high-altitude regions. The novel SNPs identified in these genes might have arisen de novo in these populations. In another approach, the FSTs of SNP-containing genes were correlated with the corresponding climatic factors. ‘Radiation in the growing season’ was the only environmental factor found to be strongly correlated with the gene-level FSTs. In both the approaches, the high light intensity was identified as the primary abiotic stress associated with the variations in these populations. The differential gene expression analysis between field and controlled condition grown plants also showed high light intensity as the primary abiotic stress, particularly for the high altitude populations. Our results provide a genome-wide perspective of nucleotide variations in populations along altitudinal gradient and their putative role in emergence of these variations.
Conditional Disease Development extracted from Longitudinal Health Care Cohort Data using Layered Network Construction
Authors: Kannan Venkateshan , Swartz Fredrik , Kiani Narsis A. , Silberberg Gilad , Tsipras Giorgos , Gomez-Cabrero David , Alexanderson Kristina , Tegnèr Jesper 
Published: May 2016

AbstractHealth care data holds great promise to be used in clinical decision support systems. However, frequent near-synonymous diagnoses recorded separately, as well as the sheer magnitude and complexity of the disease data makes it challenging to extract non-trivial conclusions beyond confirmatory associations from such a web of interactions. Here we present a systematic methodology to derive statistically valid conditional development of diseases. To this end we utilize a cohort of 5,512,469 individuals followed over 13 years at inpatient care, including data on disability pension and cause of death. By introducing a causal information fraction measure and taking advantage of the composite structure in the ICD codes, we extract an effective directed lower dimensional network representation (100 nodes and 130 edges) of our cohort. Unpacking composite nodes into bipartite graphs retrieves, for example, that individuals with behavioral disorders are more likely to be followed by prescription drug poisoning episodes, whereas women with leiomyoma were more likely to subsequently experience endometriosis. The conditional disease development represent putative causal relations, indicating possible novel clinical relationships and pathophysiological associations that have not been explored yet.
Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation
Authors: Budding Kevin , van de Graaf Eduard. A. , Kardol-Hoefnagel Tineke , Kwakkel-van Erp Johanna M. , Luijk Bart D. , Oudijk Erik-Jan D. , van Kessel Diana A. , Grutters Jan C. , Hack C. Erik , Otten Henderikus G. 
Published: May 2016

AbstractCD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx.
Regenerative repair of Pifithrin-α in cerebral ischemia via VEGF dependent manner
Authors: Zhang Ping , Lei Xuhui , Sun Ying , Zhang Haitao , Chang Liang , Li Chenlong , Liu Daming , Bhatta Nishant , Zhang Zhiren , Jiang Chuanlu 
Published: May 2016

AbstractPromoting regenerative repair, including neurogenesis and angiogenesis, may provide a new therapeutic strategy for treatment of stroke. P53, a well-documented transcription factor, has been reported to be involved in cerebral ischemia and also serves as an important regulator of vascular endothelial growth factor (VEGF). However, the role of p53 in endogenous regenerative repair after brain ischemia is poorly understood. In this study, we investigated the effects of PFT-α, a specific p53 inhibitor on neurogenesis and angiogenesis improvement and associated signal pathways in rats impaired by cerebral artery occlusion (MCAo). PFT-α induced neuroprotection, reduced infarct volume and neurological functional impairment after ischemic stroke. More importantly, neurogenesis and angiogenesis were greatly enhanced by PFT-α and accompanied by increased expression of VEGF. Moreover, we got consistent results in neural stem cells (NSCs) isolated from fetal rats. In contrast, application of the anti-VEGF neutralizing antibody (RB-222) partially reversed PFT-α-induced neuroprotection and rescued p53 expression. Noteworthily, inhibition of p53 after ischemic stroke in these rats improved their outcomes via promotion of regenerative repair. In conclusion, PFT-α could serve as a promising therapeutic strategy for ischemic stroke by promoting regenerative repair.
Strength of weak layers in cascading failures on multiplex networks: case of the international trade network
Authors: Lee Kyu-Min , Goh K.-I. 
Published: May 2016

AbstractMany real-world complex systems across natural, social, and economical domains consist of manifold layers to form multiplex networks. The multiple network layers give rise to nonlinear effect for the emergent dynamics of systems. Especially, weak layers that can potentially play significant role in amplifying the vulnerability of multiplex networks might be shadowed in the aggregated single-layer network framework which indiscriminately accumulates all layers. Here we present a simple model of cascading failure on multiplex networks of weight-heterogeneous layers. By simulating the model on the multiplex network of international trades, we found that the multiplex model produces more catastrophic cascading failures which are the result of emergent collective effect of coupling layers, rather than the simple sum thereof. Therefore risks can be systematically underestimated in single-layer network analyses because the impact of weak layers can be overlooked. We anticipate that our simple theoretical study can contribute to further investigation and design of optimal risk-averse real-world complex systems.
Increased arachidonic acid-containing phosphatidylcholine is associated with reactive microglia and astrocytes in the spinal cord after peripheral nerve injury
Authors: Xu Dongmin , Omura Takao , Masaki Noritaka , Arima Hideyuki , Banno Tomohiro , Okamoto Ayako , Hanada Mitsuru , Takei Shiro , Matsushita Shoko , Sugiyama Eiji , Setou Mitsutoshi , Matsuyama Yukihiro 
Published: May 2016

AbstractPeripheral nerve injury (PNI) triggers cellular and molecular changes in the spinal cord. However, little is known about how the polyunsaturated fatty acid-containing phosphatidylcholines (PUFA-PCs) are regulated in the spinal cord after PNI and the association of PUFA-PCs with the non-neuronal cells within in the central nervous system (CNS). In this study, we found that arachidonic acid-containing phosphatidylcholine (AA-PC), [PC(16:0/20:4)+K]+, was significantly increased in the ipsilateral ventral and dorsal horns of the spinal cord after sciatic nerve transection and the increased expression of [PC(16:0/20:4)+K]+ spatiotemporally resembled the increase of reactive microglia and the astrocytes. From the lipidomics point of view, we conclude that [PC(16:0/20:4)+K]+ could be the main phospholipid in the spinal cord influenced by PNI and the regulation of specific phospholipid molecule in the CNS after PNI is associated with the reactive microglia and astrocytes.
Arbuscular mycorrhizal symbiosis affects the grain proteome of Zea mays: a field study
Authors: Bona Elisa , Scarafoni Alessio , Marsano Francesco , Boatti Lara , Copetta Andrea , Massa Nadia , Gamalero Elisa , D’Agostino Giovanni , Cesaro Patrizia , Cavaletto Maria , Berta Graziella 
Published: May 2016

AbstractMaize is one of the most important crops worldwide and is strongly dependent on arbuscular mycorrhiza (AM) fungi, organisms that form a mutualistic association with land plants. In maize, AM symbiosis enhances spike dry weight, spike length, spike circumference and the dry weight and dimensions of the grain. Notwithstanding its ubiquitous nature, the detailed relationship between AM fungal colonization and plant development is not completely understood. To facilitate a better understanding of the effects of AM fungi on plants, the work reported here assessed the effects of a consortium of AM fungi on the kernel proteome of maize, cultivated in open-field conditions. To our knowledge, this is the first report of the modulation of a plant seed proteome following AM fungal inoculation in the field. Here, it was found that AM fungi modify the maize seed proteome by up-regulating enzymes involved in energetic metabolism, embryo development, nucleotide metabolism, seed storage and stress responses.
Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies
Authors: Andreeva T. V. , Tyazhelova T. V. , Rykalina V. N. , Gusev F. E. , Goltsov A. Yu. , Zolotareva O. I. , Aliseichik M. P. , Borodina T. A. , Grigorenko A. P. , Reshetov D. A. , Ginter E. K. , Amelina S. S. , Zinchenko R. A. , Rogaev E. I. 
Published: May 2016

AbstractTumors of the jaws may represent different human disorders and frequently associate with pathologic bone fractures. In this report, we analyzed two affected siblings from a family of Russian origin, with a history of dental tumors of the jaws, in correspondence to original clinical diagnosis of cementoma consistent with gigantiform cementoma (GC, OMIM: 137575). Whole exome sequencing revealed the heterozygous missense mutation c.1067G > A (p.Cys356Tyr) in ANO5 gene in these patients. To date, autosomal-dominant mutations have been described in the ANO5 gene for gnathodiaphyseal dysplasia (GDD, OMIM: 166260) and multiple recessive mutations have been described in the gene for muscle dystrophies (OMIM: 613319, 611307); the same amino acid (Cys) at the position 356 is mutated in GDD. These genetic data and similar clinical phenotypes demonstrate that the GC and GDD likely represent the same type of bone pathology. Our data illustrate the significance of mutations in single amino-acid position for particular bone tissue pathology. Modifying role of genetic variations in another gene on the severity of the monogenic trait pathology is also suggested. Finally, we propose the model explaining the tissue-specific manifestation of clinically distant bone and muscle diseases linked to mutations in one gene.
Novel application of hydrophobin in medical science: a drug carrier for improving serum stability
Authors: Zhao Liqiang , Xu Haijin , Li Ying , Song Dongmin , Wang Xiangxiang , Qiao Mingqiang , Gong Min 
Published: May 2016

AbstractMultiple physiological properties of glucagon-like peptide-1 (GLP-1) ensure that it is a promising drug candidate for the treatment of type 2 diabetes. However, the in vivo half-life of GLP-1 is short because of rapid degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. The poor serum stability of GLP-1 has significantly limited its clinical utility, although many studies are focused on extending the serum stability of this molecule. Hydrophobin, a self-assembling protein, was first applied as drug carrier to stabilize GLP-1 against protease degradation by forming a cavity. The glucose tolerance test clarified that the complex retained blood glucose clearance activity for 72 hours suggesting that this complex might be utilized as a drug candidate administered every 2–3 days. Additionally, it was found that the mutagenesis of hydrophobin preferred a unique pH condition for self-assembly. These findings suggested that hydrophobin might be a powerful tool as a drug carrier or a pH sensitive drug-release compound. The novel pharmaceutical applications of hydrophobin might result in future widespread interest in hydrophobin.
A Rapid Method for Refolding Cell Surface Receptors and Ligands
Authors: Zhai Lu , Wu Ling , Li Feng , Burnham Robert S. , Pizarro Juan C. , Xu Bin 
Published: May 2016

AbstractProduction of membrane-associated cell surface receptors and their ligands is often a cumbersome, expensive, and time-consuming process that limits detailed structural and functional characterization of this important class of proteins. Here we report a rapid method for refolding inclusion-body-based, recombinant cell surface receptors and ligands in one day, a speed equivalent to that of soluble protein production. This method efficiently couples modular on-column immobilized metal ion affinity purification and solid-phase protein refolding. We demonstrated the general utility of this method for producing multiple functionally active immunoreceptors, ligands, and viral decoys, including challenging cell surface proteins that cannot be produced using typical dialysis- or dilution-based refolding approaches.
A Relation for Nanodroplet Diffusion on Smooth Surfaces
Authors: Li Chu , Huang Jizu , Li Zhigang 
Published: May 2016

AbstractIn this work, we study the diffusion of nanodroplets on smooth surfaces through molecular dynamics (MD) simulations and theoretical analyses. Molecular dynamics simulations show that nanodroplet surface diffusion is different from that of single molecules and solid particles. The dependence of nanodroplet diffusion coefficient on temperature undergoes a transition from linear to nonlinear as the surface wettability is weakened due to the coupling of temperature and surface energy. We also develop a simple relation for the diffusion coefficient by using the contact angle and contact radius of the droplet. It works well for a wide range of surface wettabilities and different sized nanodroplets, as confirmed by MD simulations.
The independent contribution of miRNAs to the missing heritability in CYP3A4/5 functionality and the metabolism of atorvastatin
Authors: Liu Ju-E , Ren Bin , Tang Lan , Tang Qian-Jie , Liu Xiao-Ying , Li Xin , Bai Xue , Zhong Wan-Ping , Meng Jin-Xiu , Lin Hao-Ming , Wu Hong , Chen Ji-Yan , Zhong Shi-Long 
Published: May 2016

AbstractTo evaluate the independent contribution of miRNAs to the missing heritability in CYP3A4/5 functionality and atorvastatin metabolism, the relationships among three levels of factors, namely (1) clinical characteristics, CYP3A4/5 genotypes and miRNAs, (2) CYP3A4 and CYP3A5 mRNAs and (3) CYP3A activity, as well as their individual impacts on atorvastatin metabolism, were assessed in 55 human liver tissues. MiR-27b, miR-206 and CYP3A4 mRNA respectively accounted for 20.0%, 5.8% and 9.5% of the interindividual variations in CYP3A activity. MiR-142 was an independent contributor to the expressions of CYP3A4 mRNA (partial R2 = 0.12, P = 0.002) and CYP3A5 mRNA (partial R2 = 0.09, P = 0.005) but not CYP3A activity or atorvastatin metabolism. CYP3A activity was a unique independent predictor of variability of atorvastatin metabolism, explaining the majority of the variance in reduction of atorvastatin (60.0%) and formation of ortho-hydroxy atorvastatin (78.8%) and para-hydroxy atorvastatin (83.9%). MiR-27b and miR-206 were found to repress CYP3A4 gene expression and CYP3A activity by directly binding to CYP3A4 3′-UTR, while miR-142 was found to indirectly repress CYP3A activity. Our study indicates that miRNAs play significant roles in bridging the gap between epigenetic effects and missing heritability in CYP3A functionality.
Cell type-dependent Erk-Akt pathway crosstalk regulates the proliferation of fetal neural progenitor cells
Authors: Rhim Ji heon , Luo Xiangjian , Gao Dongbing , Xu Xiaoyun , Zhou Tieling , Li Fuhai , Wang Ping , Wong Stephen T. C. , Xia Xiaofeng 
Published: May 2016

AbstractNeural progenitor (NP) cells are the multipotent cells that produce neurons and glia in the central nervous system. Compounds regulating their proliferation are key to both understanding brain development and unlocking their potential in regenerative repair. We discuss a chemical screen that unexpectedly identified inhibitors of Erk signaling potently promoting the self-renewing divisions of fetal NP cells. This occurred through crosstalk between Erk and Akt signaling cascades. The crosstalk mechanism is cell type-specific and is not detected in adult NP cells as well as brain tumor cells. The mechanism was also shown to be independent from the GSK-3 signaling pathway, which has been reported to be a major regulator of NP cell homeostasis and inhibitors to which were also identified in the screen. In vitro Erk inhibition led to the prolonged rapid expansion of fetal NP cells while retaining their multipotency. In vivo inhibitor administration significantly inhibited the neuronal differentiation and resulted in increased proliferative progenitor cells in the ventricular/subventricular zone (VZ/SVZ) of the embryonic cortex. Our results uncovered a novel regulating pathway for NP cell proliferation in the developing brain. The discovery provides a pharmacological basis for in vitro expansion and in vivo manipulation of NP cells.
Dlg5 maintains apical polarity by promoting membrane localization of Crumbs during Drosophila oogenesis
Authors: Luo Jun , Wang Heng , Kang Di , Guo Xuan , Wan Ping , Wang Dou , Chen Jiong 
Published: May 2016

AbstractApical-basal polarity plays critical roles in the functions of epithelial tissues. However, the mechanisms of epithelial polarity establishment and maintenance remain to be fully elucidated. Here we show that the membrane-associated guanylate kinase (MAGUK) family protein Dlg5 is required for the maintenance of apical polarity of follicle epithelium during Drosophila oogenesis. Dlg5 localizes at the apical membrane and adherens junction (AJ) of follicle epithelium in early stage egg chambers. Specifically, we demonstrate that the major function of Dlg5 is to promote apical membrane localization of Crumbs, since overexpression of Crumbs but not other major apical or AJ components could rescue epithelial polarity defects resulted from loss of Dlg5. Furthermore, we performed a structure-function analysis of Dlg5 and found that the C-terminal PDZ3 and PDZ4 domains are required for all Dlg5’s functions as well as its ability to localize to apical membrane. The N-terminal coiled-coil motif could be individually targeted to the apical membrane, while the central linker region could be targeted to AJ. Lastly, the MAGUK core domains of PDZ4-SH3-GUK could be individually targeted to apical, AJ and basolateral membranes.
An inhibitor of the Keap1-Nrf2 protein-protein interaction protects NCM460 colonic cells and alleviates experimental colitis
Authors: Lu Meng-Chen , Ji Jian-Ai , Jiang Yong-Lin , Chen Zhi-Yun , Yuan Zhen-Wei , You Qi-Dong , Jiang Zheng-Yu 
Published: May 2016

AbstractUlcerative colitis (UC) is a chronic relapsing-remitting form of inflammatory bowel disease (IBD) that increases the risk of colorectal cancer, the third most common malignancy in humans. Oxidative stress is a risk factor for the development of UC. The Keap1-Nrf2-ARE pathway is one of the most important defensive mechanisms against oxidative and/or electrophilic stresses. In this study, we identified CPUY192018 as a potent small-molecule inhibitor of the Keap1-Nrf2 PPI, investigated the cyto-protective effects of CPUY192018 on the NCM460 colonic cells and evaluated whether treatment with the inhibitor of the Keap1-Nrf2 PPI exerts protection on an established experimental model of UC induced by dextran sodium sulfate (DSS). Our study clearly demonstrated that CPUY192018 had a cytoprotective effect against DSS in both NCM460 cells and mouse colon via the activation of Nrf2 signaling. These results suggested that activation of Nrf2 by directly inhibiting the Keap1-Nrf2 PPI may be beneficial as a treatment for UC.
Mesenchymal stem cells are sensitive to bleomycin treatment
Authors: Nicolay Nils H. , Rühle Alexander , Perez Ramon Lopez , Trinh Thuy , Sisombath Sonevisay , Weber Klaus-Josef , Ho Anthony D. , Debus Jürgen , Saffrich Rainer , Huber Peter E. 
Published: May 2016

AbstractMesenchymal stem cells (MSCs) have been shown to attenuate pulmonary damage induced by bleomycin-based anticancer treatments, but the influence of bleomycin on the stem cells themselves remains largely unknown. Here, we demonstrate that human bone marrow-derived MSCs are relatively sensitive to bleomycin exposure compared to adult fibroblasts. MSCs revealed increased levels of apoptosis after bleomycin treatment, while cellular morphology, stem cell surface marker expression and the ability for adhesion and migration remained unchanged. Bleomycin treatment also resulted in a reduced adipogenic differentiation potential of these stem cells. MSCs were found to efficiently repair DNA double strand breaks induced by bleomycin, mostly through non-homologous end joining repair. Low mRNA and protein expression levels of the inactivating enzyme bleomycin hydrolase were detected in MSCs that may contribute to the observed bleomycin-sensitive phenotype of these cells. The sensitivity of MSCs against bleomycin needs to be taken into consideration for ongoing and future treatment protocols investigating these stem cells as a potential treatment option for bleomycin-induced pulmonary damage in the clinic.