bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R
Authors: Pradhan Geetali , Wu Chia-Shan , Han Lee Jong , Kanikarla Preeti , Guo Shaodong , Yechoor Vijay K. , Samson Susan L. , Sun Yuxiang 
Published: April 2017

AbstractOrexigenic hormone ghrelin and anorexic hormone obestatin are encoded by the same preproghrelin gene. While it is known that ghrelin inhibits glucose-stimulated insulin secretion (GSIS), the effect of obestatin on GSIS is unclear. Ghrelin’s effect is mediated by its receptor Growth Hormone Secretagogue Receptor (GHS-R), but the physiologically relevant receptor of obestatin remains debatable. Here we have investigated the effect of obestatin on GSIS in vitro, in vivo and ex vivo, and tested whether obestatin regulates insulin secretion through GHS-R. We found that under hyperglycemic condition, obestatin augments GSIS in rat insulinoma cells (INS-1) and in pancreatic islets from ghrelin−/− mice. Surprisingly, obestatin-induced GSIS was absent in β-cells in which GHS-R was suppressed. Obestatin-induced insulin secretion was abolished in the circulation of Ghsr−/− mice, and in pancreatic islets isolated from Ghsr−/− mice. We also found that obestatin-induced GSIS was attenuated in islets isolated from β-cell-specific Ghsr knockout MIP-Cre/ERT;Ghsrf/f mice. Our data collectively demonstrate that obestatin is a potent insulin secretagogue under hyperglycemic condition, and obestatin’s effect on insulin secretion is mediated by GHS-R in pancreatic β-cells. Our findings reveal an intriguing insight that obestatin and ghrelin have opposing effects on insulin secretion, and both are mediated through ghrelin receptor GHS-R.
Growth Differentiation Factor-15 Deficiency Augments Inflammatory Response and Exacerbates Septic Heart and Renal Injury Induced by Lipopolysaccharide
Authors: Abulizi Palida , Loganathan Neruja , Zhao Duo , Mele Tina , Zhang Yixin , Zwiep Terry , Liu Kexiang , Zheng Xiufen 
Published: April 2017

AbstractSeptic acute kidney injury (AKI) and myocardial dysfunction are leading causes of mortality with no accepted method of therapy. In this study we demonstrate the role of growth differentiating factor 15 (GDF15) in septic AKI and myocardial dysfunction using a murine lipopolysaccharide (LPS)-induced sepsis model and anin vitrocell culture system. Data show that GDF15 deficiency augments inflammatory response and exacerbates renal and cardiac injury induced by LPS, while over-expression of GDF15 protects the kidney and heart from LPS-induced organ dysfunction. Therefore, this study highlights the therapeutic potential of GDF15 in the treatment of endotoxin-induced sepsis.
Tangluoning, a traditional Chinese medicine, attenuates in vivo and in vitro diabetic peripheral neuropathy through modulation of PERK/Nrf2 pathway
Authors: Yang Xinwei , Yao Weijie , Liu Haolong , Gao Yanbin , Liu Renhui , Xu Liping 
Published: April 2017

AbstractProlonged hyperglycemia-induced oxidative stress and endoplasmic reticulum stress have been demonstrated to play a key role in progression of diabetic peripheral neuropathy (DPN). PERK/ Nrf2 pathway plays a predominant role in oxidative and endoplasmic reticulum (ER) stress which is associated with cell survival. This study examined the modulation of the PERK/Nrf2 pathway and apoptosis by a traditional Chinese medicine Tangluoning (TLN) in streptozotocin-induced DPN rat models and the effects of serum TLN on the PERK/Nrf2 pathway, apoptosis, intracellular reactive oxygen species and mitochondrial membrane potential in Schwann cells cultured in 150 mM glucose. It is found that TLN attenuated oxidative and ER stress and apoptosis through the PERK/Nrf2 pathway by upregulating p-PERK, Nrf2/ARE pathways and downregulating the CHOP-related apoptosis pathways in the experimental DPN models both in vivo and in vitro.
Hinge-deleted IgG4 blocker therapy for acetylcholine receptor myasthenia gravis in rhesus monkeys
Authors: Losen Mario , Labrijn Aran F. , van Kranen-Mastenbroek Vivianne H. , Janmaat Maarten L. , Haanstra Krista G. , Beurskens Frank J. , Vink Tom , Jonker Margreet , ‘t Hart Bert A. , Mané-Damas Marina , Molenaar Peter C. , Martinez-Martinez Pilar , van der Esch Eline , Schuurman Janine , de Baets Marc H. , Parren Paul W. H. I. 
Published: April 2017

AbstractAutoantibodies against ion channels are the cause of numerous neurologic autoimmune disorders. Frequently, such pathogenic autoantibodies have a restricted epitope-specificity. In such cases, competing antibody formats devoid of pathogenic effector functions (blocker antibodies) have the potential to treat disease by displacing autoantibodies from their target. Here, we have used a model of the neuromuscular autoimmune disease myasthenia gravis in rhesus monkeys (Macaca mulatta) to test the therapeutic potential of a new blocker antibody: MG was induced by passive transfer of pathogenic acetylcholine receptor-specific monoclonal antibody IgG1-637. The effect of the blocker antibody (IgG4Δhinge-637, the hinge-deleted IgG4 version of IgG1-637) was assessed using decrement measurements and single-fiber electromyography. Three daily doses of 1.7 mg/kg IgG1-637 (cumulative dose 5 mg/kg) induced impairment of neuromuscular transmission, as demonstrated by significantly increased jitter, synaptic transmission failures (blockings) and a decrease in the amplitude of the compound muscle action potentials during repeated stimulations (decrement), without showing overt symptoms of muscle weakness. Treatment with three daily doses of 10 mg/kg IgG4Δhinge-637 significantly reduced the IgG1-637-induced increase in jitter, blockings and decrement. Together, these results represent proof-of principle data for therapy of acetylcholine receptor-myasthenia gravis with a monovalent antibody format that blocks binding of pathogenic autoantibodies.
Phenome-wide association study for CYP2A6 alleles: rs113288603 is associated with hearing loss symptoms in elderly smokers
Authors: Polimanti Renato , Jensen Kevin P. , Gelernter Joel 
Published: April 2017

AbstractTo identify novel phenotypic associations related to Cytochrome P450 Family 2 Subfamily A Member 6 (CYP2A6), we investigated the human phenome in a total of 11,271 individuals. Initially, we conducted a phenome-wide association study in 3,401 nicotine-exposed elderly subjects considering 358 phenotypic traits. We identified a significant association between CYP2A6 rs113288603 and hearing loss symptoms (p = 5.75 × 10−5). No association was observed in a sample of 3,245 nicotine-unexposed individuals from the same discovery cohort, consistent with the conclusion that the finding is related to CYP2A6 involvement in nicotine metabolism. Consistent results were obtained (p < 0.1) in an independent sample of 2,077 nicotine-exposed elderly subjects, and similarly, no significance was observed in the nicotine-unexposed sample (n = 2,548) of the replication cohort. Additional supporting evidence for this association was provided by gene expression data: rs113288603 is associated with increased CYP2A6 expression in cerebellar hemispheres (p = 7.8 × 10−4). There is a well-known correlation between smoking and age-related hearing loss. Cigarette smoking is associated with structural changes in the brain and CYP2A6 mediates these changes. In this context, the regulatory role of rs113288603 in cerebellum appears to be consistent with the known involvement of this brain region in auditory function.
Experimental evidence of Fano resonances in nanomechanical resonators
Authors: Stassi Stefano , Chiadò Alessandro , Calafiore Giuseppe , Palmara Gianluca , Cabrini Stefano , Ricciardi Carlo 
Published: April 2017

AbstractFano resonance refers to an interference between localized and continuum states that was firstly reported for atomic physics and solid-state quantum devices. In recent years, Fano interference gained more and more attention for its importance in metamaterials, nanoscale photonic devices, plasmonic nanoclusters and surface-enhanced Raman scattering (SERS). Despite such interest in nano-optics, no experimental evidence of Fano interference was reported up to now for purely nanomechanical resonators, even if classical mechanical analogies were referred from a theoretical point of view. Here we demonstrate for the first time that harmonic nanomechanical resonators with relatively high quality factors, such as cantilevers vibrating in vacuum, can show characteristic Fano asymmetric curves when coupled in arrays. The reported findings open new perspectives in fundamental aspects of classical nanomechanical resonators and pave the way to a new generation of chemical and biological nanoresonator sensors with higher parallelization capability.
Affinity biosensors using recombinant native membrane proteins displayed on exosomes: application to botulinum neurotoxin B receptor
Authors: Desplantes Richard , Lévêque Christian , Muller Benjamin , Lotierzo Manuela , Ferracci Géraldine , Popoff Michel , Seagar Michael , Mamoun Robert , El Far Oussama 
Published: April 2017

AbstractThe development of simple molecular assays with membrane protein receptors in a native conformation still represents a challenging task. Exosomes are extracellular vesicles which, due to their stability and small size, are suited for analysis in various assay formats. Here, we describe a novel approach to sort recombinant fully native and functional membrane proteins to exosomes using a targeting peptide. Specific binding of high affinity ligands to the potassium channel Kv1.2, the G-protein coupled receptor CXCR4, and the botulinum neurotoxin type B (BoNT/B) receptor, indicated their correct assembly and outside out orientation in exosomes. We then developed, using a label-free optical biosensor, a new method to determine the kinetic constants of BoNT/B holotoxin binding to its receptor synaptotagmin2/GT1b ganglioside (kon = 2.3 ×105 M−1.s−1, koff = 1.3 10−4 s−1), yielding an affinity constant (KD = 0.6 nM) similar to values determined from native tissue. In addition, the recombinant binding domain of BoNT/B, a potential vector for neuronal delivery, bound quasi-irreversibly to synaptotagmin 2/GT1b exosomes. Engineered exosomes provide thus a novel means to study membrane proteins for biotechnology and clinical applications.
Orbital angular momentum (OAM) conversion and multicasting using N-core supermode fiber
Authors: Shao Guang-hao , Yan Shao-cheng , Luo Wei , Lu Guo-Wei , Lu Yan-qing 
Published: April 2017

AbstractWe propose and numerically demonstrate a conversion and multicasting scheme of orbital angular momentum (OAM) states by using N-core supermode fiber (NCSF), where the topological charges of converted OAM states mainly depend on the injected OAM state and the number of fiber cores. The conversion efficiency (CE) of the converted OAM states could be optimized by properly designing the fiber structure. Take N = 6 as an example, ~37% CE could be achieved at telecom bands. Moreover, even for a fabricated NCSF, the CE could be dynamically changed by stretching the fiber or by adjusting the refractive index of the fiber cores through external control of the environmental conditions. Meanwhile, OAM multicasting could also be realized in the designed NCSF. The crosstalk between the multicasted OAM channels and their neighboring ones are assessed to be less than −30 dB. The proposed fiber-based OAM conversion and multicasting system is compatible with the existing optical fiber communication systems, showing potential applications in the future.
Distant Phe345 mutation compromises the stability and activity of Mycobacterium tuberculosis isocitrate lyase by modulating its structural flexibility
Authors: Shukla Harish , Shukla Rohit , Sonkar Amit , Pandey Tripti , Tripathi Timir 
Published: April 2017

AbstractIsocitrate lyase (ICL), a potential anti-tubercular drug target, catalyzes the first step of the glyoxylate shunt. In the present investigation, we studied the conformational flexibility of MtbICL to better understand its stability and catalytic activity. Our biochemical results showed that a point mutation at Phe345, which is topologically distant (>10 Å) to the active site signature sequence (189KKCGH193), completely abolishes the activity of the enzyme. In depth computational analyses were carried out for understanding the structural alterations using molecular dynamics, time-dependent secondary structure and principal component analysis. The results showed that the mutated residue increased the structural flexibility and induced conformational changes near the active site (residues 170–210) and in the C-terminal lid region (residues 411–428). Both these regions are involved in the catalytic activity of MtbICL. Upon mutation, the residual mobility of the enzyme increased, resulting in a decrease in the stability, which was confirmed by the lower free energy of stabilization in the mutant enzyme suggesting the destabilization in the structure. Our results have both biological importance and chemical novelty. It reveals internal dynamics of the enzyme structure and also suggests that regions other than the active site should be exploited for targeting MtbICL inhibition and development of novel anti-tuberculosis compounds.
Functional ectopic neuritogenesis by retinal rod bipolar cells is regulated by miR-125b-5p during retinal remodeling in RCS rats
Authors: Fu Yan , Hou Baoke , Weng Chuanhuang , Liu Weiping , Dai Jiaman , Zhao Congjian , Yin Zheng Qin 
Published: April 2017

AbstractFollowing retinal degeneration, retinal remodeling can cause neuronal microcircuits to undergo structural alterations, which particularly affect the dendrites of bipolar cells. However, the mechanisms and functional consequences of such changes remain unclear. Here, we used Royal College of Surgeon (RCS) rats as a model of retinal degeneration, to study structural changes in rod bipolar cells (RBCs) and the underlying mechanisms of these changes. We found that, with retinal degeneration, RBC dendrites extended into the outer nuclear layer (ONL) of the retina, and the ectopic dendrites formed synapses with the remaining photoreceptors. This ectopic neuritogenesis was associated with brain-derived neurotrophic factor (BDNF) – expression of which was negatively regulated by miR-125b-5p. Overexpression of miR-125b-5p in the retinae of RCS rats diminished RBC ectopic dendrites, and compromised the b-wave of the flash electroretinogram (ERG). In contrast, down-regulation of miR-125b-5p (or exogenous BDNF treatment) increased RBC ectopic dendrites, and improved b-wave. Furthermore, we showed that the regulation of ectopic neuritogenesis by BDNF occurred via the downstream modulation of the TrkB-CREB signaling pathway. Based on these findings, we conclude that ectopic dendrites are likely to be providing functional benefits and that, in RCS rats, miR-125b-5p regulates ectopic neuritogenesis by RBCs through modulation of the BDNF-TrkB-CREB pathway. This suggests that therapies that reduce miR-125b-5p expression could be beneficial in human retinal degenerative disease.
RETRACTED ARTICLE: One-step assembly of 2H-1T MoS2:Cu/reduced graphene oxide nanosheets for highly efficient hydrogen evolution
Authors: He H.-Y. 
Published: April 2017

AbstractThe transition metal dichagenides and their metallic 1T structure are attracting contemporary attentions for applications in high-performance devices because their peculiar optical and electrical properties. The single and few layers 1T structure is generally obtained by mechanical or chemical exfoliation. This work presents facile one-step synthesis of 2H-1T MoS2:Cu/reduced graphene oxide nanosheets. The experiment results indicated that the MoS2 and MoS2:Cu prepared by simple chemical solution reaction possessed 2H-1T structures. The reduced graphene oxide (rGO) incorporation further induced the phase transition from 2H-MoS2 to 1T-MoS2 and morphology transition from granular/nanosheet to more nanosheet. The 2H-1T structure and 2H → 1T phase transition, together with the Cu doping and interface effect between the MoS2 and rGO, remarkably enhanced the conduction and photoconduction of the nanostructures. Thus, Cu doping and rGO incorporation obviously enhanced the catalytic activity and its stability, making the MoS2:Cu/rGO nanosheet a most active and stable catalyst for hydrogen evolution. This work clearly indicates that the 1T-MoS2 nanosheets with high catalytic activity for hydrogen evolution can be easily obtained by the facile low temperature chemical method and induction of rGO.
Proper time regularization and the QCD chiral phase transition
Authors: Cui Zhu-Fang , Zhang Jin-Li , Zong Hong-Shi 
Published: April 2017

AbstractWe study the QCD chiral phase transition at finite temperature and finite quark chemical potential within the two flavor Nambu–Jona-Lasinio (NJL) model, where a generalization of the proper-time regularization scheme is motivated and implemented. We find that in the chiral limit the whole transition line in the phase diagram is of second order, whereas for finite quark masses a crossover is observed. Moreover, if we take into account the influence of quark condensate to the coupling strength (which also provides a possible way of how the effective coupling varies with temperature and quark chemical potential), it is found that a CEP may appear. These findings differ substantially from other NJL results which use alternative regularization schemes, some explanation and discussion are given at the end. This indicates that the regularization scheme can have a dramatic impact on the study of the QCD phase transition within the NJL model.
Transcriptome analyses of differential gene expression in the bursa of Fabricius between Silky Fowl and White Leghorn
Authors: Han Deping , Zhang Yuanyuan , Chen Jianfei , Hua Guoying , Li Junying , Deng Xuegong , Deng Xuemei 
Published: April 2017

AbstractHyperpigmentation in Silky Fowl (SF) results in aberrant immune cell development. However, how melanocytes regulate B-cell proliferation in the bursa of Fabricius (BF) is unclear. To resolve this conundrum, we collected BFs from three-week-old SF and White Leghorn (WL) female chickens for RNA sequencing. The BF development was relatively weaker in SF than in WL. The transcriptome analyses identified 4848 differentially expressed genes, 326 long noncoding RNAs (lncRNAs), and 67 microRNAs in the BF of SF. The genes associated with melanogenesis was significantly higher, but that of the genes associated with the cytokine-cytokine receptor interactions and JAK-STAT signalling pathway was significantly lower in SF than in WL. Crucial biological processes, such as the receptor activity, cell communication, and cellular responses to stimuli, were clustered in SF. The predicted target lncRNAs genes were mainly associated with cell proliferation pathways such as JAK-STAT, WNT, MAPK, and Notch signalling pathways. Except for the above pathways, the target microRNA genes were related to the metabolism, melanogenesis, autophagy, and NOD-like and Toll-like receptor signalling pathways. The lncRNAs and microRNAs were predicted to regulate the JAK2, STAT3, and IL-15 genes. Thus, B-cell development in the BF of SF might be regulated and affected by noncoding RNAs.
Overexpression of heparanase enhances T lymphocyte activities and intensifies the inflammatory response in a model of murine rheumatoid arthritis
Authors: Digre Andreas , Singh Kailash , Åbrink Magnus , Reijmers Rogier M. , Sandler Stellan , Vlodavsky Israel , Li Jin-Ping 
Published: April 2017

AbstractHeparanase is an endo-glucuronidase that degrades heparan sulfate chains. The enzyme is expressed at a low level in normal organs; however, elevated expression of heparanase has been detected in several inflammatory conditions, e.g. in the synovial joints of rheumatoid arthritis (RA) patients. Herein, we have applied the model of collagen-induced arthritis (CIA) to transgenic mice overexpressing human heparanase (Hpa-tg) along with wildtype (WT) mice. About 50% of the induced animals developed clinical symptoms, i.e. swelling of joints, and there were no differences between the Hpa-tg and WT mice in the incidence of disease. However, Hpa-tg mice displayed an earlier response and developed more severe symptoms. Examination of cells from thymus, spleen and lymph nodes revealed increased innate and adaptive immune responses of the Hpa-tg mice, reflected by increased proportions of macrophages, antigen presenting cells and plasmacytoid dendritic cells as well as Helios-positive CD4+ and CD8+ T cells. Furthermore, splenic lymphocytes from Hpa-tg mice showed higher proliferation activity. Our results suggest that elevated expression of heparanase augmented both the innate and adaptive immune system and propagated inflammatory reactions in the murine RA model.
Auditory conditioned stimulus presentation during NREM sleep impairs fear memory in mice
Authors: Purple Ross J. , Sakurai Takeshi , Sakaguchi Masanori 
Published: April 2017

AbstractExternally manipulating memories by presenting conditioned stimuli (CS) during sleep is a new approach to investigating memory processing during sleep. However, whether presenting a CS during REM or NREM sleep enhances or extinguishes fear memory has not been clearly delineated. In this study, mice underwent trace fear conditioning consisting of an auditory CS paired with a foot shock, and the auditory CS was re-presented during subsequent REM or NREM sleep. Mice that received auditory cueing during NREM but not REM sleep showed impaired fear memory upon later presentation of the auditory CS. These findings have implications for the use of cueing during sleep and advance our understanding of the role of REM and NREM sleep in memory consolidation.
New method for quantification of gasotransmitter hydrogen sulfide in biological matrices by LC-MS/MS
Authors: Tan Bo , Jin Sheng , Sun Jiping , Gu Zhongkai , Sun Xiaotian , Zhu Yichun , Huo Keke , Cao Zonglian , Yang Ping , Xin Xiaoming , Liu Xinhua , Pan Lilong , Qiu Furong , Jiang Jian , Jia Yiqun , Ye Fuyuan , Xie Ying , Zhu Yi Zhun 
Published: April 2017

AbstractHydrogen sulfide exists widely in mammalian tissues and plays a vital role in physiological and pathophysiological processes. However, striking differences with orders of magnitude were observed for the detected hydrogen sulfide concentrations in biological matrices among different measurements in literature, which lead to the uncertainty for examination the biological relevance of hydrogen sulfide. Here, we developed and validated a liquid chromatography- mass spectrometry (LC-MS/MS) method for the determination of hydrogen sulfide in various biological matrices by determination of a derivative of hydrogen sulfide and monobromobimane named sulfide dibimane (SDB).36S-labeled SDB was synthesized and validated for using as an internal standard. This method has been successfully used to measure hydrogen sulfide levels in a broad range of biological matrices, such as blood, plasma, tissues, cells, and enzymes, across different species. Moreover, a novel mode that hydrogen sulfide could loosely and non-covalently bind to human serum protein (HSA) and hemoglobin (HB) was revealed by using the developed method.