bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light-induced unfolding and refolding of supramolecular polymer nanofibres
Authors: Adhikari Bimalendu , Yamada Yuki , Yamauchi Mitsuaki , Wakita Kengo , Lin Xu , Aratsu Keisuke , Ohba Tomonori , Karatsu Takashi , Hollamby Martin J. , Shimizu Nobutaka , Takagi Hideaki , Haruki Rie , Adachi Shin-ichi , Yagai Shiki 
Published: May 2017

AbstractUnlike classical covalent polymers, one-dimensionally (1D) elongated supramolecular polymers (SPs) can be encoded with high degrees of internal order by the cooperative aggregation of molecular subunits, which endows these SPs with extraordinary properties and functions. However, this internal order has not yet been exploited to generate and dynamically control well-defined higher-order (secondary) conformations of the SP backbone, which may induce functionality that is comparable to protein folding/unfolding. Herein, we report light-induced conformational changes of SPs based on the 1D exotic stacking of hydrogen-bonded azobenzene hexamers. The stacking causes a unique internal order that leads to spontaneous curvature, which allows accessing conformations that range from randomly folded to helically folded coils. The reversible photoisomerization of the azobenzene moiety destroys or recovers the curvature of the main chain, which demonstrates external control over the SP conformation that may ultimately lead to biological functions.
TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice
Authors: Marrone Maria Cristina , Morabito Annunziato , Giustizieri Michela , Chiurchiù Valerio , Leuti Alessandro , Mattioli Marzia , Marinelli Sara , Riganti Loredana , Lombardi Marta , Murana Emanuele , Totaro Antonio , Piomelli Daniele , Ragozzino Davide , Oddi Sergio , Maccarrone Mauro , Verderio Claudia , Marinelli Silvia 
Published: May 2017

AbstractThe capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication.
Heterodimerization of Munc13 C2A domain with RIM regulates synaptic vesicle docking and priming
Authors: Camacho Marcial , Basu Jayeeta , Trimbuch Thorsten , Chang Shuwen , Pulido-Lozano Cristina , Chang Shwu-Shin , Duluvova Irina , Abo-Rady Masin , Rizo Josep , Rosenmund Christian 
Published: May 2017

AbstractThe presynaptic active zone protein Munc13 is essential for neurotransmitter release, playing key roles in vesicle docking and priming. Mechanistically, it is thought that the C2A domain of Munc13 inhibits the priming function by homodimerization, and that RIM disrupts the autoinhibitory homodimerization forming monomeric priming-competent Munc13. However, it is unclear whether the C2A domain mediates other Munc13 functions in addition to this inactivation–activation switch. Here, we utilize mutations that modulate the homodimerization and heterodimerization states to define additional roles of the Munc13 C2A domain. Using electron microscopy and electrophysiology in hippocampal cultures, we show that the C2A domain is critical for additional steps of vesicular release, including vesicle docking. Optimal vesicle docking and priming is only possible when Munc13 heterodimerizes with RIM via its C2A domain. Beyond being a switching module, our data suggest that the Munc13-RIM heterodimer is an active component of the vesicle docking, priming and release complex.
Hybrid supercapacitors for reversible control of magnetism
Authors: Molinari Alan , Leufke Philipp M. , Reitz Christian , Dasgupta Subho , Witte Ralf , Kruk Robert , Hahn Horst 
Published: May 2017

AbstractElectric field tuning of magnetism is one of the most intensely pursued research topics of recent times aiming at the development of new-generation low-power spintronics and microelectronics. However, a reversible magnetoelectric effect with an on/off ratio suitable for easy and precise device operation is yet to be achieved. Here we propose a novel route to robustly tune magnetism via the charging/discharging processes of hybrid supercapacitors, which involve electrostatic (electric-double-layer capacitance) and electrochemical (pseudocapacitance) doping. We use both charging mechanisms—occurring at the La0.74Sr0.26MnO3/ionic liquid interface to control the balance between ferromagnetic and non-ferromagnetic phases of La1−xSrxMnO3 to an unprecedented extent. A magnetic modulation of up to ≈33% is reached above room temperature when applying an external potential of only about 2.0 V. Our case study intends to draw attention to new, reversible physico-chemical phenomena in the rather unexplored area of magnetoelectric supercapacitors.
Learning stable and predictive network-based patterns of schizophrenia and its clinical symptoms
Authors: Gheiratmand Mina , Rish Irina , Cecchi Guillermo A. , Brown Matthew R. G. , Greiner Russell , Polosecki Pablo I. , Bashivan Pouya , Greenshaw Andrew J. , Ramasubbu Rajamannar , Dursun Serdar M. 
Published: May 2017

AbstractSchizophrenia is often associated with disrupted brain connectivity. However, identifying specific neuroimaging-based patterns pathognomonic for schizophrenia and related symptom severity remains a challenging open problem requiring large-scale data-driven analyses emphasizing not only statistical significance but also stability across multiple datasets, contexts and cohorts. Accurate prediction on previously unseen subjects, or generalization, is also essential for any useful biomarker of schizophrenia. In order to build a predictive model based on functional network feature patterns, we studied whole-brain fMRI functional networks, both at the voxel level and lower-resolution supervoxel level. Targeting Auditory Oddball task data on the FBIRN fMRI dataset (n = 95), we considered node-degree and link-weight network features and evaluated stability and generalization accuracy of statistically significant feature sets in discriminating patients vs. controls. We also applied sparse multivariate regression (elastic net) to whole-brain functional connectivity features, for the first time, to derive stable predictive features for symptom severity. Whole-brain link-weight features achieved 74% accuracy in identifying patients and were more stable than voxel-wise node-degrees. Link-weight features predicted severity of several negative and positive symptom scales, including inattentiveness and bizarre behavior. The most-significant, stable and discriminative functional connectivity changes involved increased correlations between thalamus and primary motor/primary sensory cortex, and between precuneus (BA7) and thalamus, putamen, and Brodmann areas BA9 and BA44. Precuneus, along with BA6 and primary sensory cortex, was also involved in predicting severity of several symptoms. Overall, the proposed multi-step methodology may help identify more reliable multivariate patterns allowing for accurate prediction of schizophrenia and its symptoms severity.
Development of a Whole Organism Platform for Phenotype-Based Analysis of IGF1R-PI3K-Akt-Tor Action
Authors: Liu Chengdong , Dai Wei , Bai Yan , Chi Changfeng , Xin Yi , He Gen , Mai Kangsen , Duan Cunming 
Published: May 2017

AbstractAberrant regulation of the insulin-like growth factor (IGF)/insulin (IIS)-PI3K-AKT-TOR signaling pathway is linked to major human diseases, and key components of this pathway are targets for therapeutic intervention. Current assays are molecular target- or cell culture-based platforms. Due to the great in vivo complexities inherited in this pathway, there is an unmet need for whole organism based assays. Here we report the development of a zebrafish transgenic line, Tg(igfbp5a:GFP), which faithfully reports the mitotic action of IGF1R-PI3K-Akt-Tor signaling in epithelial cells in real-time. This platform is well suited for high-throughput assays and real-time cell cycle analysis. Using this platform, the dynamics of epithelial cell proliferation in response to low [Ca2+] stress and the distinct roles of Torc1 and Torc2 were elucidated. The availability of Tg(igfbp5a:GFP) line provides a whole organism platform for phenotype-based discovery of novel players and inhibitors in the IIS-PI3K-Akt-Tor signaling pathway.
Using an Event-History with Risk-Free Model to Study the Genetics of Alcoholism
Authors: Yang Hsin-Chou , Chen I-Chen , Tsay Yuh-Chyuan , Li Zheng-Rong , Chen Chun-houh , Hwu Hai-Gwo , Chen Chen-Hsin 
Published: May 2017

AbstractCase–control genetic association studies typically ignore possible later disease onset in currently healthy subjects and assume that subjects with diseases equally contribute to the likelihood for inference, regardless of their onset age. Therefore, we used an event-history with risk-free model to simultaneously characterize alcoholism susceptibility and onset age in 65 independent non-Hispanic Caucasian males in the Collaborative Study on the Genetics of Alcoholism. Following data quality control, we analysed 22 single nucleotide polymorphisms (SNPs) on 12 candidate genes. The single-SNP analysis showed that the dominant minor allele of rs2134655 onDRD3increases alcoholism susceptibility; the dominant minor allele of rs1439047 onNTRK2delays the alcoholism onset age, but the additive minor allele of rs172677 onGRIN2Band the dominant minor allele of rs63319 onALDH1A1advance the alcoholism onset age; and the dominant minor allele of rs1079597 onDRD2shortens the onset age range. Similarly, multiple-SNPs analysis revealed joint effects of rs2134655, rs172677 and rs1079597, with an adjustment for habitual smoking. This study provides a more comprehensive understanding of the genetics of alcoholism than previous case–control studies.
Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness
Authors: Islam Muhymin , Brink Hannah , Blanche Syndey , DiPrete Caleb , Bongiorno Tom , Stone Nicholas , Liu Anna , Philip Anisha , Wang Gonghao , Lam Wilbur , Alexeev Alexander , Waller Edmund K. , Sulchek Todd 
Published: May 2017

AbstractThe enrichment of viable cells is an essential step to obtain effective products for cell therapy. While procedures exist to characterize the viability of cells, most methods to exclude nonviable cells require the use of density gradient centrifugation or antibody-based cell sorting with molecular labels of cell viability. We report a label-free microfluidic technique to separate live and dead cells that exploits differences in cellular stiffness. The device uses a channel with repeated ridges that are diagonal with respect to the direction of cell flow. Stiff nonviable cells directed through the channel are compressed and translated orthogonally to the channel length, while soft live cells follow hydrodynamic flow. As a proof of concept, Jurkat cells are enriched to high purity of viable cells by a factor of 185-fold. Cell stiffness was validated as a sorting parameter as nonviable cells were substantially stiffer than live cells. To highlight the utility for hematopoietic stem cell transplantation, frozen samples of cord blood were thawed and the purity of viable nucleated cells was increased from 65% to over 94% with a recovery of 73% of the viable cells. Thus, the microfluidic stiffness sorting can simply and efficiently obtain highly pure populations of viable cells.
The Topobiology of Chemical Elements in Seabird Feathers
Authors: R. Howell Nicholas , Lavers Jennifer L. , Uematsu Sayaka , Paterson David , Howard Daryl L. , Spiers Kathryn , Jonge Martin D. de , Hanley Tracey , Garrett Richard , Banati Richard B. 
Published: May 2017

AbstractThe highly organized morphogenesis of bird feathers holds important phylo- and ontogenetic information on the evolution of birds, organogenesis, tissue regeneration, and the health status of individual animals. Altered topobiological patterns are regularly used as retrospective evidence for disturbed developmental trajectories due to the past exposure to environmental stressors. Using the most advanced high-resolution (5–70 µm) X-ray fluorescence microscopy (XFM), we describe in the feathers from three species of Procellariiformes hitherto unknown, depositions of elements (Zn, Ca, Br, Cu, Fe) that are independent of pigmentation or any underlying variation in density or polymer structure. In the case of Zn, the pattern across several species of Procellariiformes, but not other species, consisted of highly regular bands of Zn numbering 30–32, which may reflect the estimated number of days of active feather growth or the duration of the moult period. Thus, speculatively, the highly consistent Zn pattern might be the result of a so far unknown diurnal systemic regulation rather than local heterogeneity amongst the follicular stem cells.
Vascular Remodelling Relates to an Elevated Oscillatory Shear Index and Relative Residence Time in Spontaneously Hypertensive Rats
Authors: Chen Zhiyan , Yu Haiyi , Shi Yue , Zhu Minjia , Wang Yueshen , Hu Xi , Zhang Youyi , Chang Yu , Xu Ming , Gao Wei 
Published: May 2017

AbstractHaemodynamic disorders are common clinical findings in hypertension and lead to adverse cardiovascular events. However, the haemodynamic conditions in hypertension models are poorly understood. This study aimed to observe the characteristics of haemodynamics in spontaneously hypertensive rats (SHRs) and antihypertensive-treated SHRs. Twenty-four adult male SHRs and Wistar-Kyoto rats (WKYs) were randomly divided into four groups and treated for 7 days as follows: WKY-CON (WKYs + saline), WKY-NIF (WKYs + nifedipine, 50 mg/kg/day), SHR-CON (SHRs + saline), and SHR-NIF (SHRs + nifedipine). Aortic computational fluid dynamics (CFD) models were simulated to obtain the haemodynamic parameters. We found that in the hypertensive (SHR-CON) and blood pressure-controlled (SHR-NIF) groups, the oscillatory shear index (OSI) and relative residence time (RRT), which are key haemodynamics indices, were markedly elevated. Furthermore, there was a correlation between both the elevated OSI and RRT with the vascular wall thickening in regions near the inner wall of the aortic arch. Our research demonstrates that haemodynamics remains disturbed even if the blood pressure is normalized. In addition, vascular remodelling may play an important role in maintaining elevated OSI and RRT values.
The role of stride frequency for walk-to-run transition in humans
Authors: Hansen Ernst Albin , Kristensen Lasse Andreas Risgaard , Nielsen Andreas Møller , Voigt Michael , Madeleine Pascal 
Published: May 2017

AbstractIt remains unclear why humans spontaneously shift from walking to running at a certain point during locomotion at gradually increasing velocity. We show that a calculated walk-to-run transition stride frequency (70.6 ± 3.2 strides min−1) agrees with a transition stride frequency (70.8 ± 3.1 strides min−1) predicted from the two stride frequencies applied during treadmill walking and running at freely chosen velocities and freely chosen stride frequencies. The agreement is based on Bland and Altman’s statistics. We found no essential mean relative difference between the two transition frequencies, i.e. −0.5% ± 4.2%, as well as limits of agreement of −8.7% and 7.7%. The particular two freely chosen stride frequencies used for prediction are considered behavioural attractors. Gait is predicted to be shifted from walking to running when the stride frequency starts getting closer to the running attractor than to the walking attractor. In particular, previous research has focussed on transition velocity and optimisation theories based on minimisation of, e.g., energy turnover or biomechanical loadings of the legs. Conversely, our data support that the central phenomenon of walk-to-run transition during human locomotion could be influenced by behavioural attractors in the form of stride frequencies spontaneously occurring during behaviourally unrestricted gait conditions of walking and running.
Global gene expression analysis provides insight into local adaptation to geothermal streams in tadpoles of the Andean toad Rhinella spinulosa
Authors: Pastenes Luis , Valdivieso Camilo , Di Genova Alex , Travisany Dante , Hart Andrew , Montecino Martín , Orellana Ariel , Gonzalez Mauricio , Gutiérrez Rodrigo A. , Allende Miguel L. , Maass Alejandro , Méndez Marco A. 
Published: May 2017

AbstractThe anuran Rhinella spinulosa is distributed along the Andes Range at altitudes that undergo wide daily and seasonal variation in temperature. One of the populations inhabits geothermal streams, a stable environment that influences life history traits such as the timing of metamorphosis. To investigate whether this population has undergone local adaptation to this unique habitat, we carried out transcriptome analyses in animals from two localities in two developmental stages (prometamorphic and metamorphic) and exposed them to two temperatures (20 and 25 °C). RNA-Seq, de novo assembly and annotation defined a transcriptome revealing 194,469 high quality SNPs, with 1,507 genes under positive selection. Comparisons among the experimental conditions yielded 1,593 differentially expressed genes. A bioinformatics search for candidates revealed a total of 70 genes that are highly likely to be implicated in the adaptive response of the population living in a stable environment, compared to those living in an environment with variable temperatures. Most importantly, the population inhabiting the geothermal environment showed decreased transcriptional plasticity and reduced genetic variation compared to its counterpart from the non-stable environment. This analysis will help to advance the understanding of the molecular mechanisms that account for the local adaptation to geothermal streams in anurans.
Three-dimensional scoring of zebrafish behavior unveils biological phenomena hidden by two-dimensional analyses
Authors: Macrì Simone , Neri Daniele , Ruberto Tommaso , Mwaffo Violet , Butail Sachit , Porfiri Maurizio 
Published: May 2017

AbstractThe study of zebrafish behavior represents a cornerstone upon which basic researchers promise to advance knowledge in life sciences. Although zebrafish swim in a three-dimensional (3D) space, their behavior in the lab is almost exclusively scored in two dimensions, whereby zebrafish are recorded using a single camera providing 2D videos. Whether this dimensional reduction preserves the reliability of data has not been addressed. Here we show that, compared to a 3D observation, 2D data are flawed by over-reporting and under-reporting of locomotory differences. Specifically, we first reconstructed 3D trajectories through the integration of synchronous information derived from two cameras, and then compared them with the original 2D views in classical experimental paradigms assessing shoaling tendency, fear, anxiety, and general locomotion. Our results suggest that traditional behavioral scoring of individual zebrafish performed in 2D may undermine data integrity, thereby requiring a general reconsideration of scoring zebrafish behavior to incorporate a 3D approach. We then demonstrate that, compared to 2D, a 3D approach requires a reduced number of subjects to achieve the same degree of validity. We anticipate these findings to largely benefit animal welfare by reducing the number of experimental subjects, without affecting statistical power.
cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells
Authors: Inda Carolina , Bonfiglio Juan José , dos Santos Claro Paula A. , Senin Sergio A. , Armando Natalia G. , Deussing Jan M. , Silberstein Susana 
Published: May 2017

AbstractCorticotropin-releasing hormone receptor 1 (CRHR1) activates the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). Both cAMP sources were shown to be required for the phosphorylation of ERK1/2 triggered by activated G protein coupled receptor (GPCR) CRHR1 in neuronal and neuroendocrine contexts. Here, we show that activated CRHR1 promotes growth arrest and neurite elongation in neuronal hippocampal cells (HT22-CRHR1 cells). By characterising CRHR1 signalling mechanisms involved in the neuritogenic effect, we demonstrate that neurite outgrowth in HT22-CRHR1 cells takes place by a sAC-dependent, ERK1/2-independent signalling cascade. Both tmACs and sAC are involved in corticotropin-releasing hormone (CRH)-mediated CREB phosphorylation and c-fos induction, but only sAC-generated cAMP pools are critical for the neuritogenic effect of CRH, further highlighting the engagement of two sources of cAMP downstream of the activation of a GPCR, and reinforcing the notion that restricted cAMP microdomains may regulate independent cellular processes.
Entanglement monogamy in three qutrit systems
Authors: Li Qiting , Cui Jianlian , Wang Shuhao , Long Gui-Lu 
Published: May 2017

AbstractBy introducing an arbitrary-dimensional multipartite entanglement measure, which is defined in terms of the reduced density matrices corresponding to all possible two partitions of the entire system, we prove that multipartite entanglement cannot be freely shared among the parties in both n-qubit systems and three-qutrit systems. Furthermore, our result implies that the satisfaction of the entanglement monogamy is related to the number of particles in the quantum system. As an application of three-qutrit monogamy inequality, we give a condition for the separability of a class of two-qutrit mixed states in a 3 ⊗ 3 system.
FGF23/FGFR4-mediated left ventricular hypertrophy is reversible
Authors: Grabner Alexander , Schramm Karla , Silswal Neerupma , Hendrix Matt , Yanucil Christopher , Czaya Brian , Singh Saurav , Wolf Myles , Hermann Sven , Stypmann Jörg , Di Marco Giovana Seno , Brand Marcus , Wacker Michael J. , Faul Christian 
Published: May 2017

AbstractFibroblast growth factor (FGF) 23 is a phosphaturic hormone that directly targets cardiac myocytes via FGF receptor (FGFR) 4 thereby inducing hypertrophic myocyte growth and the development of left ventricular hypertrophy (LVH) in rodents. Serum FGF23 levels are highly elevated in patients with chronic kidney disease (CKD), and it is likely that FGF23 directly contributes to the high rates of LVH and cardiac death in CKD. It is currently unknown if the cardiac effects of FGF23 are solely pathological, or if they potentially can be reversed. Here, we report that FGF23-induced cardiac hypertrophy is reversible in vitro and in vivo upon removal of the hypertrophic stimulus. Specific blockade of FGFR4 attenuates established LVH in the 5/6 nephrectomy rat model of CKD. Since CKD mimics a form of accelerated cardiovascular aging, we also studied age-related cardiac remodeling. We show that aging mice lacking FGFR4 are protected from LVH. Finally, FGF23 increases cardiac contractility via FGFR4, while known effects of FGF23 on aortic relaxation do not require FGFR4. Taken together, our data highlight a role of FGF23/FGFR4 signaling in the regulation of cardiac remodeling and function, and indicate that pharmacological interference with cardiac FGF23/FGFR4 signaling might protect from CKD- and age-related LVH.