bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formation of oligopeptides in high yield under simple programmable conditions
Authors: Rodriguez-Garcia Marc , Surman Andrew J. , Cooper Geoffrey J.T. , Suárez-Marina Irene , Hosni Zied , Lee Michael P. , Cronin Leroy 
Published: October 2015

AbstractMany high-yielding reactions for forming peptide bonds have been developed but these are complex, requiring activated amino-acid precursors and heterogeneous supports. Herein we demonstrate the programmable one-pot dehydration–hydration condensation of amino acids forming oligopeptide chains in around 50% yield. A digital recursive reactor system was developed to investigate this process, performing these reactions with control over parameters such as temperature, number of cycles, cycle duration, initial monomer concentration and initial pH. Glycine oligopeptides up to 20 amino acids long were formed with very high monomer-to-oligomer conversion, and the majority of these products comprised three amino acid residues or more. Having established the formation of glycine homo-oligopeptides, we then demonstrated the co-condensation of glycine with eight other amino acids (Ala, Asp, Glu, His, Lys, Pro, Thr and Val), incorporating a range of side-chain functionality.
Development of potent in vivo mutagenesis plasmids with broad mutational spectra
Authors: Badran Ahmed H. , Liu David R. 
Published: October 2015

AbstractMethods to enhance random mutagenesis in cells offer advantages over in vitro mutagenesis, but current in vivo methods suffer from a lack of control, genomic instability, low efficiency and narrow mutational spectra. Using a mechanism-driven approach, we created a potent, inducible, broad-spectrum and vector-based mutagenesis system in E. coli that enhances mutation 322,000-fold over basal levels, surpassing the mutational efficiency and spectra of widely used in vivo and in vitro methods. We demonstrate that this system can be used to evolve antibiotic resistance in wild-type E. coli in <24 h, outperforming chemical mutagens, ultraviolet light and the mutator strain XL1-Red under similar conditions. This system also enables the continuous evolution of T7 RNA polymerase variants capable of initiating transcription using the T3 promoter in <10 h. Our findings enable broad-spectrum mutagenesis of chromosomes, episomes and viruses in vivo, and are applicable to both bacterial and bacteriophage-mediated laboratory evolution platforms.
PKA antagonizes CLASP-dependent microtubule stabilization to re-localize Pom1 and buffer cell size upon glucose limitation
Authors: Kelkar Manasi , Martin Sophie G. 
Published: October 2015

AbstractCells couple growth with division and regulate size in response to nutrient availability. In rod-shaped fission yeast, cell-size control occurs at mitotic commitment. An important regulator is the DYRK-family kinase Pom1, which forms gradients from cell poles and inhibits the mitotic activator Cdr2, itself localized at the medial cortex. Where and when Pom1 modulates Cdr2 activity is unclear as Pom1 medial cortical levels remain constant during cell elongation. Here we show that Pom1 re-localizes to cell sides upon environmental glucose limitation, where it strongly delays mitosis. This re-localization is caused by severe microtubule destabilization upon glucose starvation, with microtubules undergoing catastrophe and depositing the Pom1 gradient nucleator Tea4 at cell sides. Microtubule destabilization requires PKA/Pka1 activity, which negatively regulates the microtubule rescue factor CLASP/Cls1/Peg1, reducing CLASP’s ability to stabilize microtubules. Thus, PKA signalling tunes CLASP’s activity to promote Pom1 cell side localization and buffer cell size upon glucose starvation.
Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs
Authors: Phinney Donald G. , Di Giuseppe Michelangelo , Njah Joel , Sala Ernest , Shiva Sruti , St Croix Claudette M. , Stolz Donna B. , Watkins Simon C. , Di Y. Peter , Leikauf George D. , Kolls Jay , Riches David W. H. , Deiuliis Giuseppe , Kaminski Naftali , Boregowda Siddaraju V. , McKenna David H. , Ortiz Luis A. 
Published: October 2015

AbstractMesenchymal stem cells (MSCs) and macrophages are fundamental components of the stem cell niche and function coordinately to regulate haematopoietic stem cell self-renewal and mobilization. Recent studies indicate that mitophagy and healthy mitochondrial function are critical to the survival of stem cells, but how these processes are regulated in MSCs is unknown. Here we show that MSCs manage intracellular oxidative stress by targeting depolarized mitochondria to the plasma membrane via arrestin domain-containing protein 1-mediated microvesicles. The vesicles are then engulfed and re-utilized via a process involving fusion by macrophages, resulting in enhanced bioenergetics. Furthermore, we show that MSCs simultaneously shed micro RNA-containing exosomes that inhibit macrophage activation by suppressing Toll-like receptor signalling, thereby de-sensitizing macrophages to the ingested mitochondria. Collectively, these studies mechanistically link mitophagy and MSC survival with macrophage function, thereby providing a physiologically relevant context for the innate immunomodulatory activity of MSCs.
Identifying causal gateways and mediators in complex spatio-temporal systems
Authors: Runge Jakob , Petoukhov Vladimir , Donges Jonathan F. , Hlinka Jaroslav , Jajcay Nikola , Vejmelka Martin , Hartman David , Marwan Norbert , Paluš Milan , Kurths Jürgen 
Published: October 2015

AbstractIdentifying regions important for spreading and mediating perturbations is crucial to assess the susceptibilities of spatio-temporal complex systems such as the Earth’s climate to volcanic eruptions, extreme events or geoengineering. Here a data-driven approach is introduced based on a dimension reduction, causal reconstruction, and novel network measures based on causal effect theory that go beyond standard complex network tools by distinguishing direct from indirect pathways. Applied to a data set of atmospheric dynamics, the method identifies several strongly uplifting regions acting as major gateways of perturbations spreading in the atmosphere. Additionally, the method provides a stricter statistical approach to pathways of atmospheric teleconnections, yielding insights into the Pacific–Indian Ocean interaction relevant for monsoonal dynamics. Also for neuroscience or power grids, the novel causal interaction perspective provides a complementary approach to simulations or experiments for understanding the functioning of complex spatio-temporal systems with potential applications in increasing their resilience to shocks or extreme events.
Metastable orientational order of colloidal discoids
Authors: Hsiao Lilian C. , Schultz Benjamin A. , Glaser Jens , Engel Michael , Szakasits Megan E. , Glotzer Sharon C. , Solomon Michael J. 
Published: October 2015

AbstractThe interplay between phase separation and kinetic arrest is important in supramolecular self-assembly, but their effects on emergent orientational order are not well understood when anisotropic building blocks are used. Contrary to the typical progression from disorder to order in isotropic systems, here we report that colloidal oblate discoids initially self-assemble into short, metastable strands with orientational order—regardless of the final structure. The model discoids are suspended in a refractive index and density-matched solvent. Then, we use confocal microscopy experiments and Monte Carlo simulations spanning a broad range of volume fractions and attraction strengths to show that disordered clusters form near coexistence boundaries, whereas oriented strands persist with strong attractions. We rationalize this unusual observation in light of the interaction anisotropy imparted by the discoids. These findings may guide self-assembly for anisotropic systems in which orientational order is desired, such as when tailored mechanical properties are sought.
Membrane stiffening by STOML3 facilitates mechanosensation in sensory neurons
Authors: Qi Yanmei , Andolfi Laura , Frattini Flavia , Mayer Florian , Lazzarino Marco , Hu Jing 
Published: October 2015

AbstractSensing force is crucial to maintain the viability of all living cells. Despite its fundamental importance, how force is sensed at the molecular level remains largely unknown. Here we show that stomatin-like protein-3 (STOML3) controls membrane mechanics by binding cholesterol and thus facilitates force transfer and tunes the sensitivity of mechano-gated channels, including Piezo channels. STOML3 is detected in cholesterol-rich lipid rafts. In mouse sensory neurons, depletion of cholesterol and deficiency of STOML3 similarly and interdependently attenuate mechanosensitivity while modulating membrane mechanics. In heterologous systems, intact STOML3 is required to maintain membrane mechanics to sensitize Piezo1 and Piezo2 channels. In C57BL/6N, but not STOML3−/− mice, tactile allodynia is attenuated by cholesterol depletion, suggesting that membrane stiffening by STOML3 is essential for mechanical sensitivity. Targeting the STOML3–cholesterol association might offer an alternative strategy for control of chronic pain.
Patched bimetallic surfaces are active catalysts for ammonia decomposition
Authors: Guo Wei , Vlachos Dionisios G. 
Published: October 2015

AbstractAmmonia decomposition is often used as an archetypical reaction for predicting new catalytic materials and understanding the very reason of why some reactions are sensitive on material’s structure. Core–shell or surface-segregated bimetallic nanoparticles expose outstanding activity for many heterogeneously catalysed reactions but the reasons remain elusive owing to the difficulties in experimentally characterizing active sites. Here by performing multiscale simulations in ammonia decomposition on various nickel loadings on platinum (111), we show that the very high activity of core–shell structures requires patches of the guest metal to create and sustain dual active sites: nickel terraces catalyse N−H bond breaking and nickel edge sites drive atomic nitrogen association. The structure sensitivity on these active catalysts depends profoundly on reaction conditions due to kinetically competing relevant elementary reaction steps. We expose a remarkable difference in active sites between transient and steady-state studies and provide insights into optimal material design.
Homology-directed repair in rodent zygotes using Cas9 and TALEN engineered proteins
Authors: Ménoret Séverine , De Cian Anne , Tesson Laurent , Remy Séverine , Usal Claire , Boulé Jean-Baptiste , Boix Charlotte , Fontanière Sandra , Crénéguy Alison , Nguyen Tuan H. , Brusselle Lucas , Thinard Reynald , Gauguier Dominique , Concordet Jean-Paul , Cherifi Yacine , Fraichard Alexandre , Giovannangeli Carine , Anegon Ignacio 
Published: October 2015

AbstractThe generation of genetically-modified organisms has been revolutionized by the development of new genome editing technologies based on the use of gene-specific nucleases, such as meganucleases, ZFNs, TALENs and CRISPRs-Cas9 systems. The most rapid and cost-effective way to generate genetically-modified animals is by microinjection of the nucleic acids encoding gene-specific nucleases into zygotes. However, the efficiency of the procedure can still be improved. In this work we aim to increase the efficiency of CRISPRs-Cas9 and TALENs homology-directed repair by using TALENs and Cas9 proteins, instead of mRNA, microinjected into rat and mouse zygotes along with long or short donor DNAs. We observed that Cas9 protein was more efficient at homology-directed repair than mRNA, while TALEN protein was less efficient than mRNA at inducing homology-directed repair. Our results indicate that the use of Cas9 protein could represent a simple and practical methodological alternative to Cas9 mRNA in the generation of genetically-modified rats and mice as well as probably some other mammals.
Sgf73, a subunit of SAGA complex, is required for the assembly of RITS complex in fission yeast
Authors: Deng Xiaolong , Zhou Huan , Zhang Guiping , Wang Wenchao , Mao Langyong , Zhou Xing , Yu Yao , Lu Hong 
Published: October 2015

AbstractRNA interference (RNAi) is a widespread gene-silencing mechanism and is required for heterochromatin assembly in a variety of organisms. The RNA-induced transcriptional silencing complex (RITS), composed of Ago1, Tas3 and Chp1, is a key component of RNAi machinery in fission yeast that connects short interference RNA (siRNA) and heterochromatin formation. However, the process by which RITS is assembled is not well understood. Here, we identified Sgf73, a subunit of the SAGA co-transcriptional complex, is required for pericentromeric heterochromatin silencing and the generation of siRNA. This novel role of Sgf73 is independent of enzymatic activities or structural integrity of SAGA. Instead, Sgf73 is physically associated with Ago1 and Chp1. The interactions among the subunits of the RITS, including those between Tas3 and Chp1, between Chp1 and Ago1, between Ago1 and Tas3, were all impaired by the deletion of sgf73+. Consistently, the recruitment of Ago1 and Chp1 to the pericentromeric region was abolished in sgf73Δ cells. Our study unveils a moonlighting function of a SAGA subunit. It suggests Sgf73 is a novel factor that promotes assembly of RITS and RNAi-mediated heterochromatin formation.
Exfoliation of large-area transition metal chalcogenide single layers
Authors: Magda Gábor Zsolt , Pető János , Dobrik Gergely , Hwang Chanyong , Biró László P. , Tapasztó Levente 
Published: October 2015

AbstractIsolating large-areas of atomically thin transition metal chalcogenide crystals is an important but challenging task. The mechanical exfoliation technique can provide single layers of the highest structural quality, enabling to study their pristine properties and ultimate device performance. However, a major drawback of the technique is the low yield and small (typically < 10 μm) lateral size of the produced single layers. Here, we report a novel mechanical exfoliation technique, based on chemically enhanced adhesion, yielding MoS2 single layers with typical lateral sizes of several hundreds of microns. The idea is to exploit the chemical affinity of the sulfur atoms that can bind more strongly to a gold surface than the neighboring layers of the bulk MoS2 crystal. Moreover, we found that our exfoliation process is not specific to MoS2, but can be generally applied for various layered chalcogenides including selenites and tellurides, providing an easy access to large-area 2D crystals for the whole class of layered transition metal chalcogenides.
An improved chloride-conducting channelrhodopsin for light-induced inhibition of neuronal activity in vivo
Authors: Wietek Jonas , Beltramo Riccardo , Scanziani Massimo , Hegemann Peter , Oertner Thomas G. , Wiegert J. Simon 
Published: October 2015

AbstractChannelrhodopsins are light-gated cation channels that have been widely used for optogenetic stimulation of electrically excitable cells. Replacement of a glutamic acid in the central gate with a positively charged amino acid residue reverses the ion selectivity and produces chloride-conducting ChRs (ChloCs). Expressed in neurons, published ChloCs produced a strong shunting effect but also a small, yet significant depolarization from the resting potential. Depending on the state of the neuron, the net result of illumination might therefore be inhibitory or excitatory with respect to action potential generation. Here we report two additional amino acid substitutions that significantly shift the reversal potential of improved ChloC (iChloC) to the reversal potential of endogenous GABAA receptors. As a result, light-evoked membrane depolarization was strongly reduced and spike initiation after current injection or synaptic stimulation was reliably inhibited in iChloC-transfected neurons in vitro. In the primary visual cortex of anesthetized mice, activation of iChloC suppressed spiking activity evoked by visual stimulation. Due to its high operational light sensitivity, iChloC makes it possible to inhibit neurons in a large volume of brain tissue from a small, point-like light source.
Microscopic basis for the band engineering of Mo1−xWxS2-based heterojunction
Authors: Yoshida Shoji , Kobayashi Yu , Sakurada Ryuji , Mori Shohei , Miyata Yasumitsu , Mogi Hiroyuki , Koyama Tomoki , Takeuchi Osamu , Shigekawa Hidemi 
Published: October 2015

AbstractTransition-metal dichalcogenide layered materials, consisting of a transition-metal atomic layer sandwiched by two chalcogen atomic layers, have been attracting considerable attention because of their desirable physical properties for semiconductor devices and a wide variety of pn junctions, which are essential building blocks for electronic and optoelectronic devices, have been realized using these atomically thin structures. Engineering the electronic/optical properties of semiconductors by using such heterojunctions has been a central concept in semiconductor science and technology. Here, we report the first scanning tunneling microscopy/spectroscopy (STM/STS) study on the electronic structures of a monolayer WS2/Mo1−xWxS2 heterojunction that provides a tunable band alignment. The atomically modulated spatial variation in such electronic structures, i.e., a microscopic basis for the band structure of a WS2/Mo1−xWxS2 heterojunction, was directly observed. The macroscopic band structure of Mo1−xWxS2 alloy was well reproduced by the STS spectra averaged over the surface. An electric field of as high as 80 × 106 Vm−1 was observed at the interface for the alloy with x = 0.3, verifying the efficient separation of photoexcited carriers at the interface.
Comparison of carbon-sulfur and carbon-amine bond in therapeutic drug: 4β-S-aromatic heterocyclic podophyllum derivatives display antitumor activity
Authors: Li Jian-Long , Zhao Wei , Zhou Chen , Zhang Ya-Xuan , Li Hong-Mei , Tang Ya-Ling , Liang Xin-Hua , Chen Tao , Tang Ya-Jie 
Published: October 2015

AbstractHerein is a first effort to systematically study the significance of carbon-sulfur (C-S) and carbon-amine (C-NH) bonds on the antitumor proliferation activity of podophyllum derivatives and their precise mechanism of apoptosis. Compared with the derivative modified by a C-NH bond, the derivative modified by a C-S bond exhibited superior antitumor activity, the inhibition activity of target proteins tubulin or Topo II, cell cycle arrest and apoptosis induction. Antitumor mechanistic studies showed that the death receptor and the mitochondrial apoptotic pathways were simultaneously activated by the C-S bond modified aromatic heterocyclic podophyllum derivatives with a higher cellular uptake percentage of 60–90% and induction of a higher level of reactive oxygen species (ROS). Only the mitochondrial apoptotic pathway was activated by the C-NH bond modified aromatic heterocyclic podophyllum derivatives, with a lower cellular uptake percentage of 40–50%. This study provided insight into effects of the C-S and C-NH bond modification on the improvement of the antitumor activity of Podophyllum derivatives.
Enzyme-linked DNA dendrimer nanosensors for acetylcholine
Authors: Walsh Ryan , Morales Jennifer M. , Skipwith Christopher G. , Ruckh Timothy T. , Clark Heather A. 
Published: October 2015

AbstractIt is currently difficult to measure small dynamics of molecules in the brain with high spatial and temporal resolution while connecting them to the bigger picture of brain function. A step towards understanding the underlying neural networks of the brain is the ability to sense discrete changes of acetylcholine within a synapse. Here we show an efficient method for generating acetylcholine-detecting nanosensors based on DNA dendrimer scaffolds that incorporate butyrylcholinesterase and fluorescein in a nanoscale arrangement. These nanosensors are selective for acetylcholine and reversibly respond to levels of acetylcholine in the neurophysiological range. This DNA dendrimer architecture has the potential to overcome current obstacles to sensing in the synaptic environment, including the nanoscale size constraints of the synapse and the ability to quantify the spatio-temporal fluctuations of neurotransmitter release. By combining the control of nanosensor architecture with the strategic placement of fluorescent reporters and enzymes, this novel nanosensor platform can facilitate the development of new selective imaging tools for neuroscience.
Epigenetic silencing of the XAF1 gene is mediated by the loss of CTCF binding
Authors: Victoria-Acosta Georgina , Vazquez-Santillan Karla , Jimenez-Hernandez Luis , Muñoz-Galindo Laura , Maldonado Vilma , Martinez-Ruiz Gustavo Ulises , Melendez-Zajgla Jorge 
Published: October 2015

AbstractXAF1 is a tumour suppressor gene that compromises cell viability by modulating different cellular events such as mitosis, cell cycle progression and apoptosis. In cancer, the XAF1 gene is commonly silenced by CpG-dinucleotide hypermethylation of its promoter. DNA demethylating agents induce transcriptional reactivation of XAF1, sensitizing cancer cells to therapy. The molecular mechanisms that mediate promoter CpG methylation have not been previously studied. Here, we demonstrate that CTCF interacts with the XAF1 promoter in vivo in a methylation-sensitive manner. By transgene assays, we demonstrate that CTCF mediates the open-chromatin configuration of the XAF1 promoter, inhibiting both CpG-dinucleotide methylation and repressive histone posttranslational modifications. In addition, the absence of CTCF in the XAF1 promoter inhibits transcriptional activation induced by well-known apoptosis activators. We report for the first time that epigenetic silencing of the XAF1 gene is a consequence of the loss of CTCF binding.
On the self-damping nature of densification in photonic sintering of nanoparticles
Authors: MacNeill William , Choi Chang-Ho , Chang Chih-Hung , Malhotra Rajiv 
Published: October 2015

AbstractSintering of nanoparticle inks over large area-substrates is a key enabler for scalable fabrication of patterned and continuous films, with multiple emerging applications. The high speed and ambient condition operation of photonic sintering has elicited significant interest for this purpose. In this work, we experimentally characterize the temperature evolution and densification in photonic sintering of silver nanoparticle inks, as a function of nanoparticle size. It is shown that smaller nanoparticles result in faster densification, with lower temperatures during sintering, as compared to larger nanoparticles. Further, high densification can be achieved even without nanoparticle melting. Electromagnetic Finite Element Analysis of photonic heating is coupled to an analytical sintering model, to examine the role of interparticle neck growth in photonic sintering. It is shown that photonic sintering is an inherently self-damping process, i.e., the progress of densification reduces the magnitude of subsequent photonic heating even before full density is reached. By accounting for this phenomenon, the developed coupled model better captures the experimentally observed sintering temperature and densification as compared to conventional photonic sintering models. Further, this model is used to uncover the reason behind the experimentally observed increase in densification with increasing weight ratio of smaller to larger nanoparticles.