bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hygroscopic compounds in spider aggregate glue remove interfacial water to maintain adhesion in humid conditions
Authors: Singla Saranshu , Amarpuri Gaurav , Dhopatkar Nishad , Blackledge Todd A. , Dhinojwala Ali 
Published: May 2018

AbstractAdhesion in humid environments is fundamentally challenging because of the presence of interfacial bound water. Spiders often hunt in wet habitats and overcome this challenge using sticky aggregate glue droplets whose adhesion is resistant to interfacial failure under humid conditions. The mechanism by which spider aggregate glue avoids interfacial failure in humid environments is still unknown. Here, we investigate the mechanism of aggregate glue adhesion by using interface-sensitive spectroscopy in conjunction with infrared spectroscopy. We demonstrate that glycoproteins act as primary binding agents at the interface. As humidity increases, we observe reversible changes in the interfacial secondary structure of glycoproteins. Surprisingly, we do not observe liquid-like water at the interface, even though liquid-like water increases inside the bulk with increasing humidity. We hypothesize that the hygroscopic compounds in aggregate glue sequester interfacial water. Using hygroscopic compounds to sequester interfacial water provides a novel design principle for developing water-resistant synthetic adhesives.
Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses
Authors: Clark Lars E. , Mahmutovic Selma , Raymond Donald D. , Dilanyan Taleen , Koma Takaaki , Manning John T. , Shankar Sundaresh , Levis Silvana C. , Briggiler Ana M. , Enria Delia A. , Wucherpfennig Kai W. , Paessler Slobodan , Abraham Jonathan 
Published: May 2018

AbstractWhile five arenaviruses cause human hemorrhagic fevers in the Western Hemisphere, only Junin virus (JUNV) has a vaccine. The GP1 subunit of their envelope glycoprotein binds transferrin receptor 1 (TfR1) using a surface that substantially varies in sequence among the viruses. As such, receptor-mimicking antibodies described to date are type-specific and lack the usual breadth associated with this mode of neutralization. Here we isolate, from the blood of a recipient of the live attenuated JUNV vaccine, two antibodies that cross-neutralize Machupo virus with varying efficiency. Structures of GP1–Fab complexes explain the basis for efficient cross-neutralization, which involves avoiding receptor mimicry and targeting a conserved epitope within the receptor-binding site (RBS). The viral RBS, despite its extensive sequence diversity, is therefore a target for cross-reactive antibodies with activity against New World arenaviruses of public health concern.
Minerals in the pre-settled coral Stylophora pistillata crystallize via protein and ion changes
Authors: Akiva Anat , Neder Maayan , Kahil Keren , Gavriel Rotem , Pinkas Iddo , Goobes Gil , Mass Tali 
Published: May 2018

AbstractAragonite skeletons in corals are key contributors to the storage of atmospheric CO2 worldwide. Hence, understanding coral biomineralization/calcification processes is crucial for evaluating and predicting the effect of environmental factors on this process. While coral biomineralization studies have focused on adult corals, the exact stage at which corals initiate mineralization remains enigmatic. Here, we show that minerals are first precipitated as amorphous calcium carbonate and small aragonite crystallites, in the pre-settled larva, which then evolve into the more mature aragonitic fibers characteristic of the stony coral skeleton. The process is accompanied by modulation of proteins and ions within these minerals. These findings may indicate an underlying bimodal regulation tactic adopted by the animal, with important ramification to its resilience or vulnerability toward a changing environment.
Two-photon imaging of neuronal activity in motor cortex of marmosets during upper-limb movement tasks
Authors: Ebina Teppei , Masamizu Yoshito , Tanaka Yasuhiro R. , Watakabe Akiya , Hirakawa Reiko , Hirayama Yuka , Hira Riichiro , Terada Shin-Ichiro , Koketsu Daisuke , Hikosaka Kazuo , Mizukami Hiroaki , Nambu Atsushi , Sasaki Erika , Yamamori Tetsuo , Matsuzaki Masanori 
Published: May 2018

AbstractTwo-photon imaging in behaving animals has revealed neuronal activities related to behavioral and cognitive function at single-cell resolution. However, marmosets have posed a challenge due to limited success in training on motor tasks. Here we report the development of protocols to train head-fixed common marmosets to perform upper-limb movement tasks and simultaneously perform two-photon imaging. After 2–5 months of training sessions, head-fixed marmosets can control a manipulandum to move a cursor to a target on a screen. We conduct two-photon calcium imaging of layer 2/3 neurons in the motor cortex during this motor task performance, and detect task-relevant activity from multiple neurons at cellular and subcellular resolutions. In a two-target reaching task, some neurons show direction-selective activity over the training days. In a short-term force-field adaptation task, some neurons change their activity when the force field is on. Two-photon calcium imaging in behaving marmosets may become a fundamental technique for determining the spatial organization of the cortical dynamics underlying action and cognition.
Indirect excitons in van der Waals heterostructures at room temperature
Authors: Calman E. V. , Fogler M. M. , Butov L. V. , Hu S. , Mishchenko A. , Geim A. K. 
Published: May 2018

AbstractIndirect excitons (IXs) are explored both for studying quantum Bose gases in semiconductor materials and for the development of excitonic devices. IXs were extensively studied in III–V and II–VI semiconductor heterostructures where IX range of existence has been limited to low temperatures. Here, we present the observation of IXs at room temperature in van der Waals transition metal dichalcogenide (TMD) heterostructures. This is achieved in TMD heterostructures based on monolayers of MoS2 separated by atomically thin hexagonal boron nitride. The IXs we realize in the TMD heterostructure have lifetimes orders of magnitude longer than lifetimes of direct excitons in single-layer TMD and their energy is gate controlled. The realization of IXs at room temperature establishes the TMD heterostructures as a material platform both for a field of high-temperature quantum Bose gases of IXs and for a field of high-temperature excitonic devices.
Hierarchical mechanism of amino acid sensing by the T-box riboswitch
Authors: Suddala Krishna C. , Cabello-Villegas Javier , Michnicka Malgorzata , Marshall Collin , Nikonowicz Edward P. , Walter Nils G. 
Published: May 2018

AbstractIn Gram-positive bacteria, T-box riboswitches control gene expression to maintain the cellular pools of aminoacylated tRNAs essential for protein biosynthesis. Co-transcriptional binding of an uncharged tRNA to the riboswitch stabilizes an antiterminator, allowing transcription read-through, whereas an aminoacylated tRNA does not. Recent structural studies have resolved two contact points between tRNA and Stem-I in the 5′ half of the T-box riboswitch, but little is known about the mechanism empowering transcriptional control by a small, distal aminoacyl modification. Using single-molecule fluorescence microscopy, we have probed the kinetic and structural underpinnings of tRNA binding to a glycyl T-box riboswitch. We observe a two-step mechanism where fast, dynamic recruitment of tRNA by Stem-I is followed by ultra-stable anchoring by the downstream antiterminator, but only without aminoacylation. Our results support a hierarchical sensing mechanism wherein dynamic global binding of the tRNA body is followed by localized readout of its aminoacylation status by snap-lock-based trapping.
Rapid labelling and covalent inhibition of intracellular native proteins using ligand-directed N-acyl-N-alkyl sulfonamide
Authors: Tamura Tomonori , Ueda Tsuyoshi , Goto Taiki , Tsukidate Taku , Shapira Yonatan , Nishikawa Yuki , Fujisawa Alma , Hamachi Itaru 
Published: May 2018

AbstractSelective modification of native proteins in live cells is one of the central challenges in recent chemical biology. As a unique bioorthogonal approach, ligand-directed chemistry recently emerged, but the slow kinetics limits its scope. Here we successfully overcome this obstacle using N-acyl-N-alkyl sulfonamide as a reactive group. Quantitative kinetic analyses reveal that ligand-directed N-acyl-N-alkyl sulfonamide chemistry allows for rapid modification of a lysine residue proximal to the ligand binding site of a target protein, with a rate constant of ~104 M−1 s−1, comparable to the fastest bioorthogonal chemistry. Despite some off-target reactions, this method can selectively label both intracellular and membrane-bound endogenous proteins. Moreover, the unique reactivity of N-acyl-N-alkyl sulfonamide enables the rational design of a lysine-targeted covalent inhibitor that shows durable suppression of the activity of Hsp90 in cancer cells. This work provides possibilities to extend the covalent inhibition approach that is currently being reassessed in drug discovery.
Evolutionary instability of CUG-Leu in the genetic code of budding yeasts
Authors: Krassowski Tadeusz , Coughlan Aisling Y. , Shen Xing-Xing , Zhou Xiaofan , Kominek Jacek , Opulente Dana A. , Riley Robert , Grigoriev Igor V. , Maheshwari Nikunj , Shields Denis C. , Kurtzman Cletus P. , Hittinger Chris Todd , Rokas Antonis , Wolfe Kenneth H. 
Published: May 2018

AbstractThe genetic code used in nuclear genes is almost universal, but here we report that it changed three times in parallel during the evolution of budding yeasts. All three changes were reassignments of the codon CUG, which is translated as serine (in 2 yeast clades), alanine (1 clade), or the ‘universal’ leucine (2 clades). The newly discovered Ser2 clade is in the final stages of a genetic code transition. Most species in this clade have genes for both a novel tRNASer(CAG) and an ancestral tRNALeu(CAG) to read CUG, but only tRNASer(CAG) is used in standard growth conditions. The coexistence of these alloacceptor tRNA genes indicates that the genetic code transition occurred via an ambiguous translation phase. We propose that the three parallel reassignments of CUG were not driven by natural selection in favor of their effects on the proteome, but by selection to eliminate the ancestral tRNALeu(CAG).
Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer
Authors: Jacobsen Annika , Bosch Linda J. W. , Martens-de Kemp Sanne R. , Carvalho Beatriz , Sillars-Hardebol Anke H. , Dobson Richard J. , de Rinaldis Emanuele , Meijer Gerrit A. , Abeln Sanne , Heringa Jaap , Fijneman Remond J. A. , Feenstra K. Anton 
Published: May 2018

AbstractHyperactivation of Wnt and Ras-MAPK signalling are common events in development of colorectal adenomas. Further progression from adenoma-to-carcinoma is frequently associated with 20q gain and overexpression of Aurora kinase A (AURKA). Interestingly, AURKA has been shown to further enhance Wnt and Ras-MAPK signalling. However, the molecular details of these interactions in driving colorectal carcinogenesis remain poorly understood. Here we first performed differential expression analysis (DEA) of AURKA knockdown in two colorectal cancer (CRC) cell lines with 20q gain and AURKA overexpression. Next, using an exact algorithm, Heinz, we computed the largest connected protein-protein interaction (PPI) network module of significantly deregulated genes in the two CRC cell lines. The DEA and the Heinz analyses suggest 20 Wnt and Ras-MAPK signalling genes being deregulated by AURKA, whereof β-catenin and KRAS occurred in both cell lines. Finally, shortest path analysis over the PPI network revealed eight ‘connecting genes’ between AURKA and these Wnt and Ras-MAPK signalling genes, of which UBE2D1, DICER1, CDK6 and RACGAP1 occurred in both cell lines. This study, first, confirms that AURKA influences deregulation of Wnt and Ras-MAPK signalling genes, and second, suggests mechanisms in CRC cell lines describing these interactions.
Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways
Authors: Keshavarz M. , Skill M. , Hollenhorst M. I. , Maxeiner S. , Walecki M. , Pfeil U. , Kummer W. , Krasteva-Christ G. 
Published: May 2018

AbstractThe mechanisms of controlling airway smooth muscle (ASM) tone are of utmost clinical importance as inappropriate constriction is a hallmark in asthma and chronic obstructive pulmonary disease. Receptors for acetylcholine and serotonin, two relevant mediators in this context, appear to be incorporated in specialized, cholesterol-rich domains of the plasma membrane, termed caveolae due to their invaginated shape. The structural protein caveolin-1 partly accounts for anchoring of these receptors. We here determined the role of the other major caveolar protein, caveolin-3 (cav-3), in orchestrating cholinergic and serotonergic ASM responses, utilizing newly generated cav-3 deficient mice. Cav-3 deficiency fully abrogated serotonin-induced constriction of extrapulmonary airways in organ baths while leaving intrapulmonary airways unaffected, as assessed in precision cut lung slices. The selective expression of cav-3 in tracheal, but not intrapulmonary bronchial epithelial cells, revealed by immunohistochemistry, might explain the differential effects of cav-3 deficiency on serotonergic ASM constriction. The cholinergic response of extrapulmonary airways was not altered, whereas a considerable increase was observed in cav-3−/− intrapulmonary bronchi. Thus, cav-3 differentially organizes serotonergic and cholinergic signaling in ASM through mechanisms that are specific for airways of certain caliber and anatomical position. This may allow for selective and site-specific intervention in hyperreactive states.
Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device
Authors: Ingavle Ganesh , Baillie Les , Davies Nathan , Beaton Nigel , Zheng Yishan , Mikhalovsky Sergey , Sandeman Susan 
Published: May 2018

AbstractWhilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established. In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device. We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood. In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model. This work provides proof-of-concept evidence to support the development of such alternative detoxification platforms.
Roles of Enhancer RNAs in RANKL-induced Osteoclast Differentiation Identified by Genome-wide Cap-analysis of Gene Expression using CRISPR/Cas9
Authors: Sakaguchi Yukako , Nishikawa Keizo , Seno Shigeto , Matsuda Hideo , Takayanagi Hiroshi , Ishii Masaru 
Published: May 2018

AbstractBidirectional transcription has been proposed to play a role associated with enhancer activity. Transcripts called enhancer RNAs (eRNAs) play important roles in gene regulation; however, their roles in osteoclasts are unknown. To analyse eRNAs in osteoclasts comprehensively, we used cap-analysis of gene expression (CAGE) to detect adjacent transcription start sites (TSSs) that were distant from promoters for protein-coding gene expression. When comparing bidirectional TSSs between osteoclast precursors and osteoclasts, we found that bidirectional TSSs were located in the 5′-flanking regions of the Nrp2 and Dcstamp genes. We also detected bidirectional TSSs in the intron region of the Nfatc1 gene. To investigate the role of bidirectional transcription in osteoclasts, we performed loss of function analyses using the CRISPR/Cas9 system. Targeted deletion of the DNA regions between the bidirectional TSSs led to decreased expression of the bidirectional transcripts, as well as the protein-coding RNAs of Nrp2, Dcstamp, and Nfatc1, suggesting that these transcripts act as eRNAs. Furthermore, osteoclast differentiation was impaired by targeted deletion of bidirectional eRNA regions. The combined results show that eRNAs play important roles in osteoclastogenic gene regulation, and may therefore provide novel insights to elucidate the transcriptional mechanisms that control osteoclast differentiation.
Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line
Authors: Stephenson Sarah E. M. , Aumann Timothy D. , Taylor Juliet M. , Riseley Jessica R. , Li Ruili , Mann Jeffrey R. , Tomas Doris , Lockhart Paul J. 
Published: May 2018

AbstractMutations in PARK2 (parkin) can result in Parkinson’s disease (PD). Parkin shares a bidirectional promoter with parkin coregulated gene (PACRG) and the transcriptional start sites are separated by only ~200 bp. Bidirectionally regulated genes have been shown to function in common biological pathways. Mice lacking parkin have largely failed to recapitulate the dopaminergic neuronal loss and movement impairments seen in individuals with parkin-mediated PD. We aimed to investigate the function of PACRG and test the hypothesis that parkin and PACRG function in a common pathway by generating and characterizing two novel knockout mouse lines harbouring loss of both parkin and Pacrg or Pacrg alone. Successful modification of the targeted allele was confirmed at the genomic, transcriptional and steady state protein levels for both genes. At 18–20 months of age, there were no significant differences in the behaviour of parental and mutant lines when assessed by openfield, rotarod and balance beam. Subsequent neuropathological examination suggested there was no gross abnormality of the dopaminergic system in the substantia nigra and no significant difference in the number of dopaminergic neurons in either knockout model compared to wildtype mice.
The electron distribution in the “activated” state of cytochrome c oxidase
Authors: Vilhjálmsdóttir Jóhanna , Gennis Robert B. , Brzezinski Peter 
Published: May 2018

AbstractCytochromecoxidase catalyzes reduction of O2to H2O at a catalytic site that is composed of a copper ion and heme group. The reaction is linked to translocation of four protons across the membrane for each O2reduced to water. The free energy associated with electron transfer to the catalytic site is unequal for the four electron-transfer events. Most notably, the free energy associated with reduction of the catalytic site in the oxidized cytochromecoxidase (stateO) is not sufficient for proton pumping across the energized membrane. Yet, this electron transfer is mechanistically linked to proton pumping. To resolve this apparent discrepancy, a high-energy oxidized state (denotedOH) was postulated and suggested to be populated only during catalytic turnover. The difference between statesOandOHwas suggested to be manifested in an elevated midpoint potential of CuBin the latter. This proposal predicts that one-electron reduction of cytochromecoxidase after its oxidation would yield re-reduction of essentially only CuB. Here, we investigated this process and found ~5% and ~6% reduction of hemea3and CuB, respectively, i.e. the apparent redox potentials for hemea3and CuBare lower than that of hemea.
Theory of Single-Impact Atomic Force Spectroscopy in liquids with material contrast
Authors: López-Guerra Enrique A. , Banfi Francesco , Solares Santiago D. , Ferrini Gabriele 
Published: May 2018

AbstractScanning probe microscopy has enabled nanoscale mapping of mechanical properties in important technological materials, such as tissues, biomaterials, polymers, nanointerfaces of composite materials, to name only a few. To improve and widen the measurement of nanoscale mechanical properties, a number of methods have been proposed to overcome the widely used force-displacement mode, that is inherently slow and limited to a quasi-static regime, mainly using multiple sinusoidal excitations of the sample base or of the cantilever. Here, a different approach is put forward. It exploits the unique capabilities of the wavelet transform analysis to harness the information encoded in a short duration spectroscopy experiment. It is based on an impulsive excitation of the cantilever and a single impact of the tip with the sample. It performs well in highly damped environments, which are often seen as problematic in other standard dynamic methods. Our results are very promising in terms of viscoelastic property discrimination. Their potential is oriented (but not limited) to samples that demand imaging in liquid native environments and also to highly vulnerable samples whose compositional mapping cannot be obtained through standard tapping imaging techniques.
Electron Information in Single- and Dual-Frequency Capacitive Discharges at Atmospheric Pressure
Authors: Park Sanghoo , Choe Wonho , Moon Se Youn , Shi Jian Jun 
Published: May 2018

AbstractDetermining the electron properties of weakly ionized gases, particularly in a high electron-neutral collisional condition, is a nontrivial task; thus, the mechanisms underlying the electron characteristics and electron heating structure in radio-frequency (rf) collisional discharges remain unclear. Here, we report the electrical characteristics and electron information in single-frequency (4.52 MHz and 13.56 MHz) and dual-frequency (a combination of 4.52 MHz and 13.56 MHz) capacitive discharges within the abnormal α-mode regime at atmospheric pressure. A continuum radiation-based electron diagnostic method is employed to estimate the electron density (ne) and temperature (Te). Our experimental observations reveal that time-averaged ne (7.7–14 × 1011 cm−3) and Te (1.75–2.5 eV) can be independently controlled in dual-frequency discharge, whereas such control is nontrivial in single-frequency discharge, which shows a linear increase in ne and little to no change in Te with increases in the rf input power. Furthermore, the two-dimensional spatiotemporal evolution of neutral bremsstrahlung and associated electron heating structures is demonstrated. These results reveal that a symmetric structure in electron heating becomes asymmetric (via a local suppression of electron temperature) as two-frequency power is simultaneously introduced.