bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of salt-inducible kinase 2 promotes the viability of peritoneal mesothelial cells exposed to stress of peritoneal dialysis
Authors: Wang H-H , Lin C-Y , Su S-H , Chuang C-T , Chang Y-L , Lee T-Y , Lee S-C , Chang C-J 
Published: July 2016

AbstractMaintaining mesothelial cell viability is critical to long-term successful peritoneal dialysis (PD) treatment. To clarify the viability mechanism of peritoneal mesothelial cells under PD solutions exposure, we examined the mechanisms of cellular response to this stress conditions. Here we report that the proteasome activity is inhibited when treated with PD solutions. Proteasome inhibition-mediated activation of salt-inducible kinase 2 (SIK2), an endoplasmic reticulum-resident protein, is important for mesothelial cell viability. SIK2 is mobilized to promote autophagy and protect the cells from apoptosis under PD solution or MG132 treatment. Immunofluorescence staining showed that SIK2 is colocalized with LC3B in the autophagosomes of mesothelial cells treated with PD solution or derived from patients undergoing PD treatment. SIK2 activation is likely via a two-step mechanism, upstream kinases relieving the autoinhibitory conformation of SIK2 molecule followed by autophosphorylation of Thr175 and activation of kinase activity. These results suggest that activation of SIK2 is required for the cell viability when proteasome activity is inhibited by PD solutions. Maintaining or boosting the activity of SIK2 may promote peritoneal mesothelial cell viability and evolve as a potential therapeutic target for maintaining or restoring peritoneal membrane integrity in PD therapy.
Epidemic spreading on complex networks with community structures
Authors: Stegehuis Clara , van der Hofstad Remco , van Leeuwaarden Johan S. H. 
Published: July 2016

AbstractMany real-world networks display a community structure. We study two random graph models that create a network with similar community structure as a given network. One model preserves the exact community structure of the original network, while the other model only preserves the set of communities and the vertex degrees. These models show that community structure is an important determinant of the behavior of percolation processes on networks, such as information diffusion or virus spreading: the community structure can both enforce as well as inhibit diffusion processes. Our models further show that it is the mesoscopic set of communities that matters. The exact internal structures of communities barely influence the behavior of percolation processes across networks. This insensitivity is likely due to the relative denseness of the communities.
A novel role of microRNA 17-5p in the modulation of circadian rhythm
Authors: Gao Qian , Zhou Lan , Yang Su-Yu , Cao Ji-Min 
Published: July 2016

AbstractThe circadian clock helps living organisms to adjust their physiology and behaviour to adapt environmental day-night cycles. The period length of circadian rhythm reflects the endogenous cycle transition rate and is modulated by environmental cues or internal molecules and the latter are of substantial importance but remain poorly revealed. Here, we demonstrated that microRNA 17-5p (miR-17-5p), which has been associated with tumours, was an important factor in controlling the circadian period. MiR-17-5p was rhythmically expressed in synchronised fibroblasts and mouse master clock suprachiasmatic nuclei (SCN). MiR-17-5p and the gene Clock exhibited a reciprocal regulation: miR-17-5p inhibited the translation of Clock by targeting the 3′UTR (untranslated region) of Clock mRNA, whereas the CLOCK protein directly bound to the promoter of miR-17 and enhanced its transcription and production of miR-17-5p. In addition, miR-17-5p suppressed the expression of Npas2. At the cellular level, bidirectional changes in miR-17-5p or CLOCK resulted in CRY1 elevation. Accordingly, in vivo, both increase and decrease of miR-17-5p in the mouse SCN led to an increase in CRY1 level and shortening of the free-running period. We conclude that miR-17-5p has an important role in the inspection and stabilisation of the circadian-clock period by interacting with Clock and Npas2 and potentially via the output of CRY1.
Metabolomic analysis of percutaneous fine-needle aspiration specimens of thyroid nodules: Potential application for the preoperative diagnosis of thyroid cancer
Authors: Ryoo Inseon , Kwon Hyuknam , Kim Soo Chin , Jung Seung Chai , Yeom Jeong A , Shin Hwa Seon , Cho Hye Rim , Yun Tae Jin , Choi Seung Hong , Sohn Chul-Ho , Park Sunghyouk , Kim Ji-hoon 
Published: July 2016

AbstractThyroid nodules are a very common problem. Since malignant thyroid nodules should be treated surgically, preoperative diagnosis of thyroid cancer is very crucial. Cytopathologic analysis of percutaneous fine-needle aspiration (FNA) specimens is the current gold standard for diagnosing thyroid nodules. However, this method has led to high rates of inconclusive results. Metabolomics has emerged as a useful tool in medical fields and shown great potential in diagnosing various cancers. Here, we evaluated the potential of nuclear magnetic resonance (NMR) analysis of percutaneous FNA specimens for preoperative diagnosis of thyroid cancer. We analyzed metabolome of FNA samples of papillary thyroid carcinoma (n = 35) and benign follicular nodule (n = 69) using a proton NMR spectrometer. The metabolomic profiles showed a considerable discrimination between benign and malignant nodules. Receiver operating characteristic (ROC) curve analysis indicated that seven metabolites could serve as discriminators (area under ROC curve value, 0.64–0.85). These findings demonstrated that NMR analysis of percutaneous FNA specimens of thyroid nodules can be potentially useful in the accurate and rapid preoperative diagnosis of thyroid cancer.
Non-invasive evaluation of neuroprotective drug candidates for cerebral infarction by PET imaging of mitochondrial complex-I activity
Authors: Fukuta Tatsuya , Asai Tomohiro , Ishii Takayuki , Koide Hiroyuki , Kiyokawa Chiaki , Hashimoto Masahiro , Kikuchi Takashi , Shimizu Kosuke , Harada Norihiro , Tsukada Hideo , Oku Naoto 
Published: July 2016

AbstractThe development of a diagnostic technology that can accurately determine the pathological progression of ischemic stroke and evaluate the therapeutic effects of cerebroprotective agents has been desired. We previously developed a novel PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) for detecting activity of mitochondrial complex I (MC-I). This probe was shown to visualize neuronal damage in the living brain of rodent and primate models of neurodegenerative diseases. In the present study, [18F]BCPP-EF was applied to evaluate the therapeutic effects of a neuroprotectant, liposomal FK506 (FK506-liposomes), on cerebral ischemia/reperfusion (I/R) injury in transient middle cerebral artery occlusion rats. The PET imaging using [18F]BCPP-EF showed a prominent reduction in the MC-I activity in the ischemic brain hemisphere. Treatment with FK506-liposomes remarkably increased the uptake of [18F]BCPP-EF in the ischemic side corresponding to the improvement of blood flow disorders and motor function deficits throughout the 7 days after I/R. Additionally, the PET scan could diagnose the extent of the brain damage accurately and showed the neuroprotective effect of FK506-liposomes at Day 7, at which 2, 3, 5-triphenyltetrazolium chloride staining couldn’t visualize them. Our study demonstrated that the PET technology using [18F]BCPP-EF has a potent capacity to evaluate the therapeutic effect of drug candidates in living brain.
A Redox-Nucleophilic Dual-Reactable Probe for Highly Selective and Sensitive Detection of H2S: Synthesis, Spectra and Bioimaging
Authors: Zhang Changyu , Wang Runyu , Cheng Longhuai , Li Bingjie , Xi Zhen , Yi Long 
Published: July 2016

AbstractHydrogen sulfide (H2S) is an important signalling molecule with multiple biological functions. The reported H2S fluorescent probes are majorly based on redox or nucleophilic reactions. The combination usage of both redox and nucleophilic reactions could improve the probe’s selectivity, sensitivity and stability. Herein we report a new dual-reactable probe with yellow turn-on fluorescence for H2S detection. The sensing mechanism of the dual-reactable probe was based on thiolysis of NBD (7-nitro-1,2,3-benzoxadiazole) amine (a nucleophilic reaction) and reduction of azide to amine (a redox reaction). Compared with its corresponding single-reactable probes, the dual-reactable probe has higher selectivity and fluorescence turn-on fold with magnitude of multiplication from that of each single-reactable probe. The highly selective and sensitive properties enabled the dual-reactable probe as a useful tool for efficiently sensing H2S in aqueous buffer and in living cells.
Scattering engineering in continuously shaped metasurface: An approach for electromagnetic illusion
Authors: Guo Yinghui , Yan Lianshan , Pan Wei , Shao Liyang 
Published: July 2016

AbstractThe control of electromagnetic waves scattering is critical in wireless communications and stealth technology. Discrete metasurfaces not only increase the design and fabrication complex but also cause difficulties in obtaining simultaneous electric and optical functionality. On the other hand, discontinuous phase profiles fostered by discrete systems inevitably introduce phase noises to the scattering fields. Here we propose the principle of a scattering-harness mechanism by utilizing continuous gradient phase stemming from the spin-orbit interaction via sinusoidal metallic strips. Furthermore, by adjusting the amplitude and period of the sinusoidal metallic strip, the scattering characteristics of the underneath object can be greatly changed and thus result in electromagnetic illusion. The proposal is validated by full-wave simulations and experiment characterization in microwave band. Our approach featured by continuous phase profile, polarization independent performance and facile implementation may find widespread applications in electromagnetic wave manipulation.
Expression patterns, mutation detection and RNA interference of Rhopalosiphum padi voltage-gated sodium channel genes
Authors: Zuo Yayun , Peng Xiong , Wang Kang , Lin Fangfei , Li Yuting , Chen Maohua 
Published: July 2016

AbstractThe voltage-gated sodium channel (VGSC) is the target of sodium-channel-blocking insecticides. Traditionally, animals were thought to have only one VGSC gene comprising a α-subunit with four homologous domains (DI–DIV). The present study showed that Rhopalosiphum padi, an economically important crop pest, owned a unique heterodimeric VGSC (H1 and H2 subunits) encoded by two genes (Rpvgsc1 and Rpvgsc2), which is unusual in insects and other animals. The open reading frame (ORF) of Rpvgsc1 consisted 1150 amino acids, and the ORF of Rpvgsc2 had 957 amino acids. Rpvgsc1 showed 64.1% amino acid identity to DI–DII of Drosophila melanogaster VGSC and Rpvgsc2 showed 64.0% amino acid identity to DIII–DIV of D. melanogaster VGSC. A M918L mutation previously reported in pyrethroids-resistant strains of other insects was found in the IIS4-S6 region of R. padi field sample. The two R. padi VGSC genes were expressed at all developmental stages and showed similar expression patterns after treatment with beta-cypermethrin. Knockdown of Rpvgsc1 or Rpvgsc2 caused significant reduction in mortality rate of R. padi after exposure to beta-cypermethrin. These findings suggest that the two R. padi VGSC genes are both functional genes.
Fusion of the mouse IgG1 Fc domain to the VHH fragment (ARP1) enhances protection in a mouse model of rotavirus
Authors: Günaydın Gökçe , Yu Shengze , Gräslund Torbjörn , Hammarström Lennart , Marcotte Harold 
Published: July 2016

AbstractA variable fragment of a heavy chain antibody (VHH) directed against rotavirus, also referred to as anti-rotavirus protein 1 (ARP1), was shown to confer protection against rotavirus induced diarrhea in infant mouse model of rotavirus induced diarrhea. In this study, we have fused the mouse IgG1 Fc to ARP1 to improve the protective capacity of ARP1 by inducing an Fc-mediated effector function. We have shown that the Fc-ARP1 fusion protein confers significantly increased protection against rotavirus in a neonatal mouse model of rotavirus-induced diarrhea by reducing the prevalence, duration and severity of diarrhea and the viral load in the small intestines, suggesting that the Fc part of immunoglobulins may be engaged in Fc-mediated neutralization of rotavirus. Engineered conventional-like antibodies, by fusion of the Fc part of immunoglobulins to antigen-specific heavy-chain only VHH fragments, might be applied to novel antibody-based therapeutic approaches to enhance elimination of pathogens by activation of distinct effector signaling pathways.
MicroRNA-mediated target mRNA cleavage and 3′-uridylation in human cells
Authors: Xu Kai , Lin Jing , Zandi Roza , Roth Jack A. , Ji Lin 
Published: July 2016

AbstractMicroRNAs (miRNAs) play an important role in targeted gene silencing by facilitating posttranscriptional and translational repression. However, the precise mechanism of mammalian miRNA-mediated gene silencing remains to be elucidated. Here, we used a stem-loop array reverse-transcription polymerase chain reaction assay to analyse miRNA-induced mRNA recognition, cleavage, posttranscriptional modification and degradation. We detected endogenous let-7 miRNA-induced and Argonaute-catalysed endonucleolytic cleavage on target mRNAs at various sites within partially paired miRNA:mRNA sequences. Most of the cleaved mRNA 5′-fragments were 3′-oligouridylated by activities of terminal uridylyl transferases (TUTases) in miRNA-induced silencing complexes and temporarily accumulated in the cytosol for 5′-3′ degradation or other molecular fates. Some 3′-5′ decayed mRNA fragments could also be captured by the miRNA-induced silencing complex stationed at the specific miRNA:mRNA target site and oligouridylated by other TUTases at its proximity without involving Argonaute-mediated RNA cleavage. Our findings provide new insights into the molecular mechanics of mammalian miRNA-mediated gene silencing by coordinated target mRNA recognition, cleavage, uridylation and degradation.
Uncalculating cooperation is used to signal trustworthiness
Authors: Jordan Jillian J. , Hoffman Moshe , Nowak Martin A. , Rand David G. 
Published: July 2016

SignificanceHuman prosociality presents an evolutionary puzzle, and reciprocity has emerged as a dominant explanation: cooperating today can bring benefits tomorrow. Reciprocity theories clearly predict that people should only cooperate when the benefits outweigh the costs, and thus that the decision to cooperate should always depend on a cost–benefit analysis. Yet human cooperation can be very uncalculating: good friends grant favors without asking questions, romantic love “blinds” us to the costs of devotion, and ethical principles make universal moral prescriptions. Here, we provide the first evidence, to our knowledge, that reputation effects drive uncalculating cooperation. We demonstrate, using economic game experiments, that people engage in uncalculating cooperation to signal that they can be relied upon to cooperate in the future.
Constituents and functional implications of the rat default mode network
Authors: Hsu Li-Ming , Liang Xia , Gu Hong , Brynildsen Julia K. , Stark Jennifer A. , Ash Jessica A. , Lin Ching-Po , Lu Hanbing , Rapp Peter R. , Stein Elliot A. , Yang Yihong 
Published: July 2016

Significance
The default mode network (DMN) has been suggested to support a variety of internal-state functions in human. Because preclinical models can be used in translational studies of neuropsychiatric disorders, investigations of the DMN in these models may aid the understanding of both physiology and pathophysiology of the human DMN. To our knowledge, this is the first study to investigate the constituents and functional implications of the rat DMN. We provide empirical evidence that the rat DMN is composed of highly connected anatomical and functional subnetworks, which show differential modulation in association with age-related cognitive dysfunction. These findings provide a framework to further explore the physiological basis and behavioral significance of the rodent DMN.
Charge transport network dynamics in molecular aggregates
Authors: Jackson Nicholas E. , Chen Lin X. , Ratner Mark A. 
Published: July 2016

Significance
Time-dependent network analysis is used to describe the structural dynamics underpinning electron transport in disordered aggregates of molecular materials, advancing understanding of how charges move through noncrystalline aggregates. Specifically, our methodology allows for the characterization of how collective, dynamic fluctuations in the 3N nuclear degrees of freedom of the disordered multimolecule aggregate impact the statistically averaged charge motion through that aggregate. Our results describe the characteristic timescales over which electron hopping competes with nuclear reorganization, providing insight into the fundamental timescales governing charge transport in disordered systems.
Conformational selectivity in cytochrome P450 redox partner interactions
Authors: Hollingsworth Scott A. , Batabyal Dipanwita , Nguyen Brian D. , Poulos Thomas L. 
Published: July 2016

SignificanceCytochrome P450 activates molecular oxygen to hydroxylate various molecules. This process requires the transfer of electrons from a redox partner, which further requires formation of a specific protein–protein complex. A question of increasing importance is whether or not the interaction between the P450 and its redox partner results in functionally important structural changes required for activity. The present work addresses the question of whether the redox partner favors binding to a specific conformer. This question is critically important in understanding how P450s activate molecular oxygen.
Spatial organization of the Ran pathway by microtubules in mitosis
Authors: Oh Doogie , Yu Che-Hang , Needleman Daniel J. 
Published: July 2016

Significance
How nanometer-sized proteins produce micron-scale subcellular organization is poorly understood. Here we study the spatial organization of the ras-related nuclear protein (Ran) pathway in mitosis. Our results reveal that whereas the upstream components of this pathway are well described as a reaction-diffusion system the downstream components exhibit more complex behaviors in which their association with microtubules causes them to be enriched in the spindle region. Because the Ran pathway influences the nucleation of microtubules, this suggests the presence of feedback based on spatial localization, in which the Ran pathway generates the microtubules that localize it. We argue that such feedback between soluble signaling pathways and the cytoskeleton have functional consequences with general implications for subcellular organization.
Numerical and experimental study of the redistribution of energetic and impurity ions by sawteeth in ASDEX Upgrade
Authors: Jaulmes F. , Geiger B. , Odstrčil T. , Weiland M. , Salewski M. , Jacobsen A.S. , Rasmussen J. , Stejner M. , Nielsen S.K. , Westerhof E. 
Published: July 2016

Abstract
In the non-linear phase of a sawtooth, the complete reconnection of field lines around the q  =  1 flux surface often occurs resulting in a radial displacement of the plasma core. A complete time-dependent electromagnetic model of this type of reconnection has been developed and implemented in the EBdyna_go code. This contribution aims at studying the behaviour of ions, both impurity and fast particles, in the pattern of reconnecting field lines during sawtoothing plasma experiments in the ASDEX Upgrade tokamak by using the newly developed numerical framework. Simulations of full reconnection with tungsten impurity that include the centrifugal force are achieved and recover the soft x-ray measurements. Based on this full-reconnection description of the sawtooth, a simple tool dedicated to estimate the duration of the reconnection is introduced. This work then studies the redistribution of fast ions during several experimentally observed sawteeth. In some cases of sawteeth at ASDEX Upgrade, full reconnection is not always observed or expected so the code gives an upper estimate of the actual experimental redistribution. The results of detailed simulations of the crashes are compared with measurements from various diagnostics such as collective Thomson scattering and fast-ion D-alpha (FIDA) spectroscopy, including FIDA tomography. A convincing qualitative agreement is found in different parts of velocity space.
Protection of Brain Injury by Amniotic Mesenchymal Stromal Cell-Secreted Metabolites
Authors: Pischiutta Francesca , Brunelli Laura , Romele Pietro , Silini Antonietta , Sammali Eliana , Paracchini Lara , Marchini Sergio , Talamini Laura , Bigini Paolo , Boncoraglio Giorgio B. , Pastorelli Roberta , De Simoni Maria-Grazia , Parolini Ornella , Zanier Elisa R. 
Published: July 2016

Objectives:To define the features of human amniotic mesenchymal stromal cell secretome and its protective properties in experimental models of acute brain injury.Design:Prospective experimental study.Setting:Laboratory research.Subjects:C57Bl/6 mice.Interventions:Mice subjected to sham or traumatic brain injury by controlled cortical impact received human amniotic mesenchymal stromal cells or phosphate-buffered saline infused intracerebroventricularly or intravenously 24 hours after injury. Organotypic cortical brain slices exposed to ischemic injury by oxygen-glucose deprivation were treated with human amniotic mesenchymal stromal cells or with their secretome (conditioned medium) in a transwell system.Measurements and Main Results:Traumatic brain injured mice receiving human amniotic mesenchymal stromal cells intravenously or intracerebroventricularly showed early and lasting functional and anatomical brain protection. cortical slices injured by oxigen-glucose deprivation and treated with human amniotic mesenchymal stromal cells or conditioned medium showed comparable protective effects (neuronal rescue, promotion of M2 microglia polarization, induction of trophic factors) indicating that the exposure of human amniotic mesenchymal stromal cells to the injured tissue is not necessary for the release of bioactive factors. Using sequential size-exclusion and gel-filtration chromatography, we identified a conditioned medium subfraction, which specifically displays these highly protective properties and we found that this fraction was rich in bioactive molecules with molecular weight smaller than 700 Da. Quantitative RNA analysis and mass spectrometry-based peptidomics showed that the active factors are not proteins or RNAs. The metabolomic profiling of six metabolic classes identified a list of molecules whose abundance was selectively elevated in the active conditioned medium fraction.Conclusions:Human amniotic mesenchymal stromal cell-secreted factors protect the brain after acute injury. Importantly, a fraction rich in metabolites, and containing neither proteic nor ribonucleic molecules was protective. This study indicates the profiling of protective factors that could be useful in cell-free therapeutic approaches for acute brain injury.