bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation induced cochaperone unfolding promotes kinase recruitment and client class-specific Hsp90 phosphorylation
Authors: Bachman Ashleigh B. , Keramisanou Dimitra , Xu Wanping , Beebe Kristin , Moses Michael A. , Vasantha Kumar M. V. , Gray Geoffrey , Noor Radwan Ebna , van der Vaart Arjan , Neckers Len , Gelis Ioannis 
Published: January 2018

AbstractDuring the Hsp90-mediated chaperoning of protein kinases, the core components of the machinery, Hsp90 and the cochaperone Cdc37, recycle between different phosphorylation states that regulate progression of the chaperone cycle. We show that Cdc37 phosphorylation at Y298 results in partial unfolding of the C-terminal domain and the population of folding intermediates. Unfolding facilitates Hsp90 phosphorylation at Y197 by unmasking a phosphopeptide sequence, which serves as a docking site to recruit non-receptor tyrosine kinases to the chaperone complex via their SH2 domains. In turn, Hsp90 phosphorylation at Y197 specifically regulates its interaction with Cdc37 and thus affects the chaperoning of only protein kinase clients. In summary, we find that by providing client class specificity, Hsp90 cochaperones such as Cdc37 do not merely assist in client recruitment but also shape the post-translational modification landscape of Hsp90 in a client class-specific manner.
Genetic analyses favour an ancient and natural origin of elephants on Borneo
Authors: Sharma Reeta , Goossens Benoit , Heller Rasmus , Rasteiro Rita , Othman Nurzhafarina , Bruford Michael W. , Chikhi Lounès 
Published: January 2018

AbstractThe origin of the elephant on the island of Borneo remains elusive. Research has suggested two alternative hypotheses: the Bornean elephant stems either from a recent introduction in the 17th century or from an ancient colonization several hundreds of thousands years ago. Lack of elephant fossils has been interpreted as evidence for a very recent introduction, whereas mtDNA divergence from other Asian elephants has been argued to favor an ancient colonization. We investigated the demographic history of Bornean elephants using full-likelihood and approximate Bayesian computation analyses. Our results are at odds with both the recent and ancient colonization hypotheses, and favour a third intermediate scenario. We find that genetic data favour a scenario in which Bornean elephants experienced a bottleneck during the last glacial period, possibly as a consequence of the colonization of Borneo, and from which it has slowly recovered since. Altogether the data support a natural colonization of Bornean elephants at a time when large terrestrial mammals could colonise from the Sunda shelf when sea levels were much lower. Our results are important not only in understanding the unique history of the colonization of Borneo by elephants, but also for their long-term conservation.
Multiple losses of photosynthesis and convergent reductive genome evolution in the colourless green algae Prototheca
Authors: Suzuki Shigekatsu , Endoh Rikiya , Manabe Ri-ichiroh , Ohkuma Moriya , Hirakawa Yoshihisa 
Published: January 2018

AbstractAutotrophic eukaryotes have evolved by the endosymbiotic uptake of photosynthetic organisms. Interestingly, many algae and plants have secondarily lost the photosynthetic activity despite its great advantages. Prototheca and Helicosporidium are non-photosynthetic green algae possessing colourless plastids. The plastid genomes of Prototheca wickerhamii and Helicosporidium sp. are highly reduced owing to the elimination of genes related to photosynthesis. To gain further insight into the reductive genome evolution during the shift from a photosynthetic to a heterotrophic lifestyle, we sequenced the plastid and nuclear genomes of two Prototheca species, P. cutis JCM 15793 and P. stagnora JCM 9641, and performed comparative genome analyses among trebouxiophytes. Our phylogenetic analyses using plastid- and nucleus-encoded proteins strongly suggest that independent losses of photosynthesis have occurred at least three times in the clade of Prototheca and Helicosporidium. Conserved gene content among these non-photosynthetic lineages suggests that the plastid and nuclear genomes have convergently eliminated a similar set of photosynthesis-related genes. Other than the photosynthetic genes, significant gene loss and gain were not observed in Prototheca compared to its closest photosynthetic relative Auxenochlorella. Although it remains unclear why loss of photosynthesis occurred in Prototheca, the mixotrophic capability of trebouxiophytes likely made it possible to eliminate photosynthesis.
Testosterone boosts physical activity in male mice via dopaminergic pathways
Authors: Jardí Ferran , Laurent Michaël R. , Kim Nari , Khalil Rougin , De Bundel Dimitri , Van Eeckhaut Ann , Van Helleputte Lawrence , Deboel Ludo , Dubois Vanessa , Schollaert Dieter , Decallonne Brigitte , Carmeliet Geert , Van den Bosch Ludo , D’Hooge Rudi , Claessens Frank , Vanderschueren Dirk 
Published: January 2018

AbstractLow testosterone (T) in men, especially its free fraction, has been associated with loss of energy. In accordance, orchidectomy (ORX) in rodents results in decreased physical activity. Still, the mechanisms through which T stimulates activity remain mostly obscure. Here, we studied voluntary wheel running behavior in three different mouse models of androgen deficiency: ORX, androgen receptor (AR) knock-out (ARKO) and sex hormone binding globulin (SHBG)-transgenic mice, a novel mouse model of “low free T”. Our results clearly show a fast and dramatic action of T stimulating wheel running, which is not explained by its action on muscle, as evidenced by neuromuscular studies and in a muscle-specific conditional ARKO mouse model. The action of T occurs via its free fraction, as shown by the results in SHBG-transgenic mice, and it implies both androgenic and estrogenic pathways. Both gene expression and functional studies indicate that T modulates the in vivo sensitivity to dopamine (DA) agonists. Furthermore, the restoration of wheel running by T is inhibited by treatment with DA antagonists. These findings reveal that the free fraction of T, both via AR and indirectly through aromatization into estrogens, stimulates physical activity behavior in male mice by acting on central DA pathways.
Symmetric Decomposition of Asymmetric Games
Authors: Tuyls Karl , Pérolat Julien , Lanctot Marc , Ostrovski Georg , Savani Rahul , Leibo Joel Z , Ord Toby , Graepel Thore , Legg Shane 
Published: January 2018

AbstractWe introduce new theoretical insights into two-population asymmetric games allowing for an elegant symmetric decomposition into two single population symmetric games. Specifically, we show how an asymmetric bimatrix game (A,B) can be decomposed into its symmetric counterparts by envisioning and investigating the payoff tables (A and B) that constitute the asymmetric game, as two independent, single population, symmetric games. We reveal several surprising formal relationships between an asymmetric two-population game and its symmetric single population counterparts, which facilitate a convenient analysis of the original asymmetric game due to the dimensionality reduction of the decomposition. The main finding reveals that if (x,y) is a Nash equilibrium of an asymmetric game (A,B), this implies that y is a Nash equilibrium of the symmetric counterpart game determined by payoff table A, and x is a Nash equilibrium of the symmetric counterpart game determined by payoff table B. Also the reverse holds and combinations of Nash equilibria of the counterpart games form Nash equilibria of the asymmetric game. We illustrate how these formal relationships aid in identifying and analysing the Nash structure of asymmetric games, by examining the evolutionary dynamics of the simpler counterpart games in several canonical examples.
Blockade of TRPV1 Inhibits Methamphetamine-induced Rewarding Effects
Authors: Tian Yu-Hua , Ma Shi-Xun , Lee Kwang-Wook , Wee Sunmee , Koob George F. , Lee Seok-Yong , Jang Choon-Gon 
Published: January 2018

AbstractMethamphetamine (MAP) is the most widely used psychostimulant in the world, but the exact mechanisms underlying MAP addiction are not yet fully understood. Recent studies have identified the distribution of TRPV1 in several brain regions that are related to drug addiction, including nucleus accumbens (NAc) and dorsal striatum (DSt). In the present study, we performed conditioned place preference (CPP) and self-administration tests to examine the effects of capsazepine (CPZ) and SB366791 (SB) on MAP reward. We found that both CPZ and SB significantly inhibited MAP-induced CPP and self-administration; in contrast, TRPV1 knock-out (KO) mice did not develop MAP-induced CPP. Real-time RT-PCR, Western blot and quantitative autoradiographic tests showed up-regulation of TRPV1 mRNA and protein expression in the NAc and/or DSt regions of mice exhibiting MAP-induced CPP. In addition, an in vivo microdialysis experiment showed that CPZ dramatically reduced dopamine (DA) levels in the NAc region of MAP-treated mice. Furthermore, attenuated dopamine transporter (DAT) binding levels in the NAc and DSt regions of MAP-induced CPP mice were reversed by CPZ. Together, these data suggest that TRPV1 plays an important role in MAP reward via the modulation of DA release and DAT density, thereby providing a novel therapeutic target for MAP addiction.
Stimulation of Epicardial Sympathetic Nerves at Different Sites Induces Cardiac Electrical Instability to Various Degrees
Authors: Wang Liang , Sun Lin , Wang Kun , Jin Yingying , Liu Qing , Xia Zhongnan , Liu Xudong , Zhang Jiakun , Li Jingjie 
Published: January 2018

AbstractThe cardiac sympathetic nerves distribute across cardiac tissues with uneven density. Yet, to what extent this anatomical heterogeneity affects electrical activity of the left ventricle is largely unknown. Dogs were randomized into non-stimulation control (NC), posterior basal-stimulation (PB), anterior superior-stimulation (AS), apical part-stimulation (AP) group. The epicardial sympathetic nerves at different sites along their distribution were with electrical stimulation (ES) for 4 hours except in the NC group. The myocardial effective refractory period (ERP), ventricular fibrillation threshold (VFT) and density of sympathetic nerves were recorded. Compared with ES at other places, the stimulation at PB site significantly shortened ERP (left ventricular anterior and posterior walls; PB group, 118 ± 4 ms, 106 ± 2 ms; Versus NC group, 155 ± 3.5 ms, 160 ± 3 ms; p < 0.01) and VFT (PB group, 11.5 ± 1.5 V; Versus NC group, 20.5 ± 0.9 V; p < 0.01), and induced remarkable regeneration of the cardiac sympathetic nerves, hence influencing electrical activity of the left ventricle to the most extent. Our study demonstrates that the degree of induced ventricular electrical instability is correlated tightly with the density of sympathetic nerves around ES site, and PB site is a potential target for modulating ventricular electrical activity to the maximal extent.
Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin- furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord Injury
Authors: Yamane Kentaro , Mazaki Tetsuro , Shiozaki Yasuyuki , Yoshida Aki , Shinohara Kensuke , Nakamura Mariko , Yoshida Yasuhiro , Zhou Di , Kitajima Takashi , Tanaka Masato , Ito Yoshihiro , Ozaki Toshifumi , Matsukawa Akihiro 
Published: January 2018

AbstractThe treatment of spinal cord injury (SCI) is currently a significant challenge. Hepatocyte growth factor (HGF) is a multipotent neurotrophic and neuroregenerative factor that can be beneficial for the treatment of SCI. However, immobilized HGF targeted to extracellular matrix may be more effective than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF remained in the spinal cord for 7 days after a single administration, while unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA) hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single administration of CBD-HGF enhanced recovery from spinal cord compression injury compared with HGF, as determined by motor recovery, and electrophysiological and immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. These results suggest that engineered CBD-HGF has superior therapeutic effects than naïve HGF. CBD-HGF combined with hydrogel scaffold may be promising for the treatment of serious SCI.
Ocular and Clinical Characteristics Associated with the Extent of Posterior Lamina Cribrosa Curve in Normal Tension Glaucoma
Authors: Lee Seung Hyen , Kim Tae-Woo , Lee Eun Ji , Girard Michaël J. A. , Mari Jean Martial , Ritch Robert 
Published: January 2018

AbstractAlthough normal-tension glaucoma (NTG) is pathogenetically heterogenous, there have been few attempts to subclassify NTG patients according to the mechanism and anatomy of optic nerve damage. This cross-sectional study was performed to investigate differences in the clinical and ocular characteristics between NTG patient groups stratified according to the degree of posterior lamina cribrosa (LC) curve which was assessed by calculating LC curvature index (LCCI). A total of 101 eyes of 101 treatment naïve NTG patients were included. The optic nerve head was imaged using enhanced-depth-imaging spectral-domain optical coherence tomography in three horizontal B-scan images in each eye. The patients were divided into two groups based on the magnitude of LCCI using a cutoff of known upper 95 percentile value in healthy subjects: a steeply curved LC group (Group 1, 75 eyes, 74.3%) and a relatively flat LC group (Group 2, 26 eyes, 25.7%). NTG eyes with relatively flat LC had lower intraocular pressure, and were associated with greater parapapillary structural alternation and systemic risk factors. These data suggest that assessment of LC morphology may help clinicians seek additional risk factors and make inferences about the mechanism of optic nerve damage in individual patients.
Sensing Native Protein Solution Structures Using a Solid-state Nanopore: Unraveling the States of VEGF
Authors: Varongchayakul Nitinun , Huttner Diana , Grinstaff Mark W. , Meller Amit 
Published: January 2018

AbstractMonitoring individual proteins in solution while simultaneously obtaining tertiary and quaternary structural information is challenging. In this study, translocation of the vascular endothelial growth factor (VEGF) protein through a solid-state nanopore (ssNP) produces distinct ion-current blockade amplitude levels and durations likely corresponding to monomer, dimer, and higher oligomeric states. Upon changing from a non-reducing to a reducing condition, ion-current blockage events from the monomeric state dominate, consistent with the expected reduction of the two inter-chain VEGF disulfide bonds. Cleavage by plasmin and application of either a positive or a negative NP bias results in nanopore signals corresponding either to the VEGF receptor recognition domain or to the heparin binding domain, accordingly. Interestingly, multi-level analysis of VEGF events reveals how individual domains affect their translocation pattern. Our study shows that careful characterization of ssNP results elucidates real-time structural information about the protein, thereby complementing classical techniques for structural analysis of proteins in solution with the added advantage of quantitative single-molecule resolution of native proteins.
Silver Nanoparticles in the Water Environment in Malaysia: Inspection, characterization, removal, modeling, and future perspective
Authors: Syafiuddin Achmad , Salmiati Salmiati , Hadibarata Tony , Kueh Ahmad Beng Hong , Salim Mohd Razman , Zaini Muhammad Abbas Ahmad 
Published: January 2018

AbstractThe current status of silver nanoparticles (AgNPs) in the water environment in Malaysia was examined and reported. For inspection, two rivers and two sewage treatment plants (STPs) were selected. Two activated carbons derived from oil palm (ACfOPS) and coconut (ACfCS) shells were proposed as the adsorbent to remove AgNPs. It was found that the concentrations of AgNPs in the rivers and STPs are in the ranges of 0.13 to 10.16 mg L−1 and 0.13 to 20.02 mg L−1, respectively, with the highest concentration measured in July. ACfOPS and ACfCS removed up to 99.6 and 99.9% of AgNPs, respectively, from the water. The interaction mechanism between AgNPs and the activated carbon surface employed in this work was mainly the electrostatic force interaction via binding Ag+ with O− presented in the activated carbon to form AgO. Fifteen kinetic models were compared statistically to describe the removal of AgNPs. It was found that the experimental adsorption data can be best described using the mixed 1,2-order model. Therefore, this model has the potential to be a candidate for a general model to describe AgNPs adsorption using numerous materials, its validation of which has been confirmed with other material data from previous works.
Interference experiment with asymmetric double slit by using 1.2-MV field emission transmission electron microscope
Authors: Harada Ken , Akashi Tetsuya , Niitsu Kodai , Shimada Keiko , Ono Yoshimasa A. , Shindo Daisuke , Shinada Hiroyuki , Mori Shigeo 
Published: January 2018

AbstractAdvanced electron microscopy technologies have made it possible to perform precise double-slit interference experiments. We used a 1.2-MV field emission electron microscope providing coherent electron waves and a direct detection camera system enabling single-electron detections at a sub-second exposure time. We developed a method to perform the interference experiment by using an asymmetric double-slit fabricated by a focused ion beam instrument and by operating the microscope under a “pre-Fraunhofer” condition, different from the Fraunhofer condition of conventional double-slit experiments. Here, pre-Fraunhofer condition means that each single-slit observation was performed under the Fraunhofer condition, while the double-slit observations were performed under the Fresnel condition. The interference experiments with each single slit and with the asymmetric double slit were carried out under two different electron dose conditions: high-dose for calculation of electron probability distribution and low-dose for each single electron distribution. Finally, we exemplified the distribution of single electrons by color-coding according to the above three types of experiments as a composite image.
Shape-matching soft mechanical metamaterials
Authors: Mirzaali M. J. , Janbaz S. , Strano M. , Vergani L. , Zadpoor A. A. 
Published: January 2018

AbstractArchitectured materials with rationally designed geometries could be used to create mechanical metamaterials with unprecedented or rare properties and functionalities. Here, we introduce “shape-matching” metamaterials where the geometry of cellular structures comprising auxetic and conventional unit cells is designed so as to achieve a pre-defined shape upon deformation. We used computational models to forward-map the space of planar shapes to the space of geometrical designs. The validity of the underlying computational models was first demonstrated by comparing their predictions with experimental observations on specimens fabricated with indirect additive manufacturing. The forward-maps were then used to devise the geometry of cellular structures that approximate the arbitrary shapes described by random Fourier’s series. Finally, we show that the presented metamaterials could match the contours of three real objects including a scapula model, a pumpkin, and a Delft Blue pottery piece. Shape-matching materials have potential applications in soft robotics and wearable (medical) devices.
Recurrent wheezing in neonatal pneumonia is associated with combined infection with Respiratory Syncytial Virus and Staphylococcus aureus or Klebsiella pneumoniae
Authors: Zhong Qin , Feng Hui , Lu Qi , Liu Xu , Zhao Qi , Du Yue , Zhang Xian-Hong , Wang Jia-Rong 
Published: January 2018

AbstractBoth viral and bacterial infections can be associated with wheezing episodes in children; however, information regarding combined infections with both viral and bacterial pathogens in full term neonates is limited. We sought to investigate the effects of viral–bacterial codetection on pneumonia severity and recurrent wheezing. A retrospective cohort study was conducted on neonates admitted to our hospital with pneumonia from 2009 to 2015. Of 606 total cases, 341 were diagnosed with RSV only, and 265 were diagnosed with both RSV and a potential bacterial pathogen. The leading four species of bacteria codetected with RSV were Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Enterobacter cloacae. Neonates with RSV and a potential bacterial pathogen were significantly more likely to have worse symptoms, higher C-reactive protein values and more abnormal chest x-ray manifestations with Bonferroni correction for multiple comparisons (P < 0.01). On Cox regression analysis, an increased risk of recurrent wheezing was found for neonates positive for RSV–Staphylococcus aureus and RSV–Klebsiella pneumoniae. Our findings indicate that the combination of bacteria and RSV in the neonatal airway is associated with more serious clinical characteristics. The presence of RSV and Staphylococcus aureus or Klebsiella pneumoniae may provide predictive markers for wheeze.
Predicted impact of thermal power generation emission control measures in the Beijing-Tianjin-Hebei region on air pollution over Beijing, China
Authors: Wang Liqiang , Li Pengfei , Yu Shaocai , Mehmood Khalid , Li Zhen , Chang Shucheng , Liu Weiping , Rosenfeld Daniel , Flagan Richard C. , Seinfeld John H. 
Published: January 2018

AbstractWidespread economic growth in China has led to increasing episodes of severe air pollution, especially in major urban areas. Thermal power plants represent a particularly important class of emissions. Here we present an evaluation of the predicted effectiveness of a series of recently proposed thermal power plant emission controls in the Beijing-Tianjin-Hebei (BTH) region on air quality over Beijing using the Community Multiscale Air Quality(CMAQ) atmospheric chemical transport model to predict CO, SO2, NO2, PM2.5, and PM10 levels. A baseline simulation of the hypothetical removal of all thermal power plants in the BTH region is predicted to lead to 38%, 23%, 23%, 24%, and 24% reductions in current annual mean levels of CO, SO2, NO2, PM2.5, and PM10 in Beijing, respectively. Similar percentage reductions are predicted in the major cities in the BTH region. Simulations of the air quality impact of six proposed thermal power plant emission reduction strategies over the BTH region provide an estimate of the potential improvement in air quality in the Beijing metropolitan area, as a function of the time of year.