bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cytoskeleton adaptor protein ankyrin-1 is upregulated by p53 following DNA damage and alters cell migration
Authors: Hall A E , Lu W-T , Godfrey J D , Antonov A V , Paicu C , Moxon S , Dalmay T , Wilczynska A , Muller P A J , Bushell M 
Published: April 2016

AbstractThe integrity of the genome is maintained by a host of surveillance and repair mechanisms that are pivotal for cellular function. The tumour suppressor protein p53 is a major component of the DNA damage response pathway and plays a vital role in the maintenance of cell-cycle checkpoints. Here we show that a microRNA, miR-486, and its host gene ankyrin-1 (ANK1) are induced by p53 following DNA damage. Strikingly, the cytoskeleton adaptor protein ankyrin-1 was induced over 80-fold following DNA damage. ANK1 is upregulated in response to a variety of DNA damage agents in a range of cell types. We demonstrate that miR-486-5p is involved in controlling G1/S transition following DNA damage, whereas the induction of the ankyrin-1 protein alters the structure of the actin cytoskeleton and sustains limited cell migration during DNA damage. Importantly, we found that higher ANK1 expression correlates with decreased survival in cancer patients. Thus, these observations highlight ANK1 as an important effector downstream of the p53 pathway.
Iterative protecting group-free cross-coupling leading to chiral multiply arylated structures
Authors: Crudden Cathleen M. , Ziebenhaus Christopher , Rygus Jason P. G. , Ghozati Kazem , Unsworth Phillip J. , Nambo Masakazu , Voth Samantha , Hutchinson Marieke , Laberge Veronique S. , Maekawa Yuuki , Imao Daisuke 
Published: April 2016

AbstractThe Suzuki–Miyaura cross-coupling is one of the most often utilized reactions in the synthesis of pharmaceutical compounds and conjugated materials. In its most common form, the reaction joins two sp2-functionalized carbon atoms to make a biaryl or diene/polyene unit. These substructures are widely found in natural products and small molecules and thus the Suzuki–Miyaura cross-coupling has been proposed as the key reaction for the automated assembly of such molecules, using protecting group chemistry to affect iterative coupling. We present herein, a significant advance in this approach, in which multiply functionalized cross-coupling partners can be employed in iterative coupling without the use of protecting groups. To accomplish this, the orthogonal reactivity of different boron substituents towards the boron-to-palladium transmetalation reaction is exploited. The approach is illustrated in the preparation of chiral enantioenriched compounds, which are known to be privileged structures in active pharmaceutical compounds.
Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite
Authors: Dankwa Selasi , Lim Caeul , Bei Amy K. , Jiang Rays H. Y. , Abshire James R. , Patel Saurabh D. , Goldberg Jonathan M. , Moreno Yovany , Kono Maya , Niles Jacquin C. , Duraisingh Manoj T. 
Published: April 2016

AbstractPlasmodium knowlesi is a zoonotic parasite transmitted from macaques causing malaria in humans in Southeast Asia. Plasmodium parasites bind to red blood cell (RBC) surface receptors, many of which are sialylated. While macaques synthesize the sialic acid variant N-glycolylneuraminic acid (Neu5Gc), humans cannot because of a mutation in the enzyme CMAH that converts N-acetylneuraminic acid (Neu5Ac) to Neu5Gc. Here we reconstitute CMAH in human RBCs for the reintroduction of Neu5Gc, which results in enhancement of P. knowlesi invasion. We show that two P. knowlesi invasion ligands, PkDBPβ and PkDBPγ, bind specifically to Neu5Gc-containing receptors. A human-adapted P. knowlesi line invades human RBCs independently of Neu5Gc, with duplication of the sialic acid-independent invasion ligand, PkDBPα and loss of PkDBPγ. Our results suggest that absence of Neu5Gc on human RBCs limits P. knowlesi invasion, but that parasites may evolve to invade human RBCs through the use of sialic acid-independent pathways.
Serial interactome capture of the human cell nucleus
Authors: Conrad Thomas , Albrecht Anne-Susann , de Melo Costa Veronica Rodrigues , Sauer Sascha , Meierhofer David , Ørom Ulf Andersson 
Published: April 2016

AbstractNovel RNA-guided cellular functions are paralleled by an increasing number of RNA-binding proteins (RBPs). Here we present ‘serial RNA interactome capture’ (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)–RNA–protein complexes that enables global RBP detection with high specificity. We apply serIC to the nuclei of proliferating K562 cells to obtain the first human nuclear RNA interactome. The domain composition of the 382 identified nuclear RBPs markedly differs from previous IC experiments, including few factors without known RNA-binding domains that are in good agreement with computationally predicted RNA binding. serIC extends the number of DNA–RNA-binding proteins (DRBPs), and reveals a network of RBPs involved in p53 signalling and double-strand break repair. serIC is an effective tool to couple global RBP capture with additional selection or labelling steps for specific detection of highly purified RBPs.
4D Visualization of replication foci in mammalian cells corresponding to individual replicons
Authors: Chagin V. O. , Casas-Delucchi C. S. , Reinhart M. , Schermelleh L. , Markaki Y. , Maiser A. , Bolius J. J. , Bensimon A. , Fillies M. , Domaing P. , Rozanov Y. M. , Leonhardt H. , Cardoso M. C. 
Published: April 2016

AbstractSince the pioneering proposal of the replicon model of DNA replication 50 years ago, the predicted replicons have not been identified and quantified at the cellular level. Here, we combine conventional and super-resolution microscopy of replication sites in live and fixed cells with computational image analysis. We complement these data with genome size measurements, comprehensive analysis of S-phase dynamics and quantification of replication fork speed and replicon size in human and mouse cells. These multidimensional analyses demonstrate that replication foci (RFi) in three-dimensional (3D) preserved somatic mammalian cells can be optically resolved down to single replicons throughout S-phase. This challenges the conventional interpretation of nuclear RFi as replication factories, that is, the complex entities that process multiple clustered replicons. Accordingly, 3D genome organization and duplication can be now followed within the chromatin context at the level of individual replicons.
Real-time imaging of glutamate clearance reveals normal striatal uptake in Huntington disease mouse models
Authors: Parsons Matthew P. , Vanni Matthieu P. , Woodard Cameron L. , Kang Rujun , Murphy Timothy H. , Raymond Lynn A. 
Published: April 2016

AbstractIt has become well accepted that Huntington disease (HD) is associated with impaired glutamate uptake, resulting in a prolonged time-course of extracellular glutamate that contributes to excitotoxicity. However, the data supporting this view come largely from work in synaptosomes, which may overrepresent nerve-terminal uptake over astrocytic uptake. Here, we quantify real-time glutamate dynamics in HD mouse models by high-speed imaging of an intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) and electrophysiological recordings of synaptically activated transporter currents in astrocytes. These techniques reveal a disconnect between the results obtained in synaptosomes and those in situ. Exogenous glutamate uptake is impaired in synaptosomes, whereas real-time measures of glutamate clearance in the HD striatum are normal or even accelerated, particularly in the aggressive R6/2 model. Our results highlight the importance of quantifying glutamate dynamics under endogenous release conditions, and suggest that the widely cited uptake impairment in HD does not contribute to pathogenesis.
Chemical ordering suppresses large-scale electronic phase separation in doped manganites
Authors: Zhu Yinyan , Du Kai , Niu Jiebin , Lin Lingfang , Wei Wengang , Liu Hao , Lin Hanxuan , Zhang Kai , Yang Tieying , Kou Yunfang , Shao Jian , Gao Xingyu , Xu Xiaoshan , Wu Xiaoshan , Dong Shuai , Yin Lifeng , Shen Jian 
Published: April 2016

AbstractFor strongly correlated oxides, it has been a long-standing issue regarding the role of the chemical ordering of the dopants on the physical properties. Here, using unit cell by unit cell superlattice growth technique, we determine the role of chemical ordering of the Pr dopant in a colossal magnetoresistant (La1−yPry)1−xCaxMnO3 (LPCMO) system, which has been well known for its large length-scale electronic phase separation phenomena. Our experimental results show that the chemical ordering of Pr leads to marked reduction of the length scale of electronic phase separations. Moreover, compared with the conventional Pr-disordered LPCMO system, the Pr-ordered LPCMO system has a metal–insulator transition that is ∼100 K higher because the ferromagnetic metallic phase is more dominant at all temperatures below the Curie temperature.
Morphological remodeling of C. elegans neurons during aging is modified by compromised protein homeostasis
Authors: Vayndorf Elena M , Scerbak Courtney , Hunter Skyler , Neuswanger Jason R , Toth Marton , Parker J Alex , Neri Christian , Driscoll Monica , Taylor Barbara E 
Published: April 2016

AbstractUnderstanding cellular outcomes, such as neuronal remodeling, that are common to both healthy and diseased aging brains is essential to the development of successful brain aging strategies. Here, we used Caenorhabdits elegans to investigate how the expression of proteotoxic triggers, such as polyglutamine (polyQ)-expanded huntingtin and silencing of proteostasis regulators, such as the ubiquitin–proteasome system (UPS) and protein clearance components, may impact the morphological remodeling of individual neurons as animals age. We examined the effects of disrupted proteostasis on the integrity of neuronal cytoarchitecture by imaging a transgenic C. elegans strain in which touch receptor neurons express the first 57 amino acids of the human huntingtin (Htt) gene with expanded polyQs (128Q) and by using neuron-targeted RNA interference in adult wild-type neurons to knockdown genes encoding proteins involved in proteostasis. We found that proteostatic challenges conferred by polyQ-expanded Htt and knockdown of specific genes involved in protein homeostasis can lead to morphological changes that are restricted to specific domains of specific neurons. The age-associated branching of PLM neurons is suppressed by N-ter polyQ-expanded Htt expression, whereas ALM neurons with polyQ-expanded Htt accumulate extended outgrowths and other soma abnormalities. Furthermore, knockdown of genes important for ubiquitin-mediated degradation, lysosomal function, and autophagy modulated these age-related morphological changes in otherwise normal neurons. Our results show that the expression of misfolded proteins in neurodegenerative disease such as Huntington’s disease modifies the morphological remodeling that is normally associated with neuronal aging. Our results also show that morphological remodeling of healthy neurons during aging can be regulated by the UPS and other proteostasis pathways. Collectively, our data highlight a model in which morphological remodeling during neuronal aging is strongly affected by disrupted proteostasis and expression of disease-associated, misfolded proteins such as human polyQ-Htt species.
Critical controllability in proteome-wide protein interaction network integrating transcriptome
Authors: Ishitsuka Masayuki , Akutsu Tatsuya , Nacher Jose C. 
Published: April 2016

AbstractRecently, the number of essential gene entries has considerably increased. However, little is known about the relationships between essential genes and their functional roles in critical network control at both the structural (protein interaction network) and dynamic (transcriptional) levels, in part because the large size of the network prevents extensive computational analysis. Here, we present an algorithm that identifies the critical control set of nodes by reducing the computational time by 180 times and by expanding the computable network size up to 25 times, from 1,000 to 25,000 nodes. The developed algorithm allows a critical controllability analysis of large integrated systems composed of a transcriptome- and proteome-wide protein interaction network for the first time. The data-driven analysis captures a direct triad association of the structural controllability of genes, lethality and dynamic synchronization of co-expression. We believe that the identified optimized critical network control subsets may be of interest as drug targets; thus, they may be useful for drug design and development.
3D Imaging of Water-Drop Condensation on Hydrophobic and Hydrophilic Lubricant-Impregnated Surfaces
Authors: Kajiya Tadashi , Schellenberger Frank , Papadopoulos Periklis , Vollmer Doris , Butt Hans-Jürgen 
Published: April 2016

AbstractCondensation of water from the atmosphere on a solid surface is an ubiquitous phenomenon in nature and has diverse technological applications, e.g. in heat and mass transfer. We investigated the condensation kinetics of water drops on a lubricant-impregnated surface, i.e., a micropillar array impregnated with a non-volatile ionic liquid. Growing and coalescing drops were imaged in 3D using a laser scanning confocal microscope equipped with a temperature and humidity control. Different stages of condensation can be discriminated. On a lubricant-impregnated hydrophobic micropillar array these are: (1) Nucleation on the lubricant surface. (2) Regular alignment of water drops between micropillars and formation of a three-phase contact line on a bottom of the substrate. (3) Deformation and bridging by coalescence which eventually leads to a detachment of the drops from the bottom substrate. The drop-substrate contact does not result in breakdown of the slippery behaviour. Contrary, on a lubricant-impregnated hydrophilic micropillar array, the condensed water drops replace the lubricant. Consequently, the surface loses its slippery property. Our results demonstrate that a Wenzel-like to Cassie transition, required to maintain the facile removal of condensed water drops, can be induced by well-chosen surface hydrophobicity.
A novel therapeutic strategy of lipidated promiscuous peptide against Mycobacterium tuberculosis by eliciting Th1 and Th17 immunity of host
Authors: Rai Pradeep K , Chodisetti Sathi Babu , Nadeem Sajid , Maurya Sudeep K , Gowthaman Uthaman , Zeng Weiguang , Janmeja Ashok K , Jackson David C , Agrewala Javed N 
Published: April 2016

AbstractRegardless of the fact that potent drug-regimen is currently available, tuberculosis continues to kill 1.5 million people annually. Tuberculosis patients are not only inflicted by the trauma of disease but they also suffer from the harmful side-effects, immune suppression and drug resistance instigated by prolonged therapy. It is an exigency to introduce radical changes in the existing drug-regime and discover safer and better therapeutic measures. Hence, we designed a novel therapeutic strategy by reinforcing the efficacy of drugs to kill Mtb by concurrently boosting host immunity by L91. L91 is chimera of promiscuous epitope of Acr1 antigen of Mtb and TLR-2 agonist Pam2Cys. The adjunct therapy using drugs and L91 (D-L91) significantly declined the bacterial load in Mtb infected animals. The mechanism involved was through enhancement of IFN-γ+TNF-α+ polyfunctional Th1 cells and IL-17A+IFN-γ+ Th17 cells, enduring memory CD4 T cells and downregulation of PD-1. The down-regulation of PD-1 prevents CD4 T cells from undergoing exhaustion and improves their function against Mtb. Importantly, the immune response observed in animals could be replicated using T cells of tuberculosis patients on drug therapy. In future, D-L91 therapy can invigorate drugs potency to treat tuberculosis patients and reduce the dose and duration of drug-regime.
Gossip Versus Punishment: The Efficiency of Reputation to Promote and Maintain Cooperation
Authors: Wu Junhui , Balliet Daniel , Van Lange Paul A. M. 
Published: April 2016

AbstractPrior theory suggests that reputation spreading (e.g., gossip) and punishment are two key mechanisms to promote cooperation in groups, but no behavioral research has yet examined their relative effectiveness and efficiency in promoting and maintaining cooperation. To examine these issues, we observed participants interacting in a four-round public goods game (PGG) with or without gossip and punishment options and a subsequent two-round trust game (TG). We manipulated gossip as the option to send notes about other group members to these members’ future partners and punishment as the option to assign deduction points to reduce other group members’ outcomes with a fee-to-fine ratio of 1:3. Findings revealed that in the four-round PGG, the option to gossip increased both cooperation and individual earnings, whereas the option to punish had no overall effect on cooperation (but a positive effect on cooperation in the last two rounds of the PGG) and significantly decreased individual earnings. Importantly, the initial option to gossip made people more trusting and trustworthy in the subsequent TG when gossip was no longer possible, compared to the no-gossip condition. Thus, we provide some initial evidence that gossip may be more effective and efficient than punishment to promote and maintain cooperation.
Dual-functional Memory and Threshold Resistive Switching Based on the Push-Pull Mechanism of Oxygen Ions
Authors: Huang Yi-Jen , Chao Shih-Chun , Lien Der-Hsien , Wen Cheng-Yen , He Jr-Hau , Lee Si-Chen 
Published: April 2016

AbstractThe combination of nonvolatile memory switching and volatile threshold switching functions of transition metal oxides in crossbar memory arrays is of great potential for replacing charge-based flash memory in very-large-scale integration. Here, we show that the resistive switching material structure, (amorphous TiOx)/(Ag nanoparticles)/(polycrystalline TiOx), fabricated on the textured-FTO substrate with ITO as the top electrode exhibits both the memory switching and threshold switching functions. When the device is used for resistive switching, it is forming-free for resistive memory applications with low operation voltage (<±1 V) and self-compliance to current up to 50 μA. When it is used for threshold switching, the low threshold current is beneficial for improving the device selectivity. The variation of oxygen distribution measured by energy dispersive X-ray spectroscopy and scanning transmission electron microscopy indicates the formation or rupture of conducting filaments in the device at different resistance states. It is therefore suggested that the push and pull actions of oxygen ions in the amorphous TiOx and polycrystalline TiOx films during the voltage sweep account for the memory switching and threshold switching properties in the device.
Optical Magnetic Induction Tomography of the Heart
Authors: Marmugi Luca , Renzoni Ferruccio 
Published: April 2016

AbstractAtrial Fibrillation (AF) affects a significant fraction of the ageing population, causing a high level of morbidity and mortality. Despite its significance, the causes of AF are still not uniquely identified. This, combined with the lack of precise diagnostic and guiding tools, makes the clinical treatment of AF sub-optimal. We identify magnetic induction tomography as the most promising technique for the investigation of the causes of fibrillation and for its clinical practice. We therefore propose a novel optical instrument based on optical atomic magnetometers, fulfilling the requirements for diagnostic mapping of the heart’s conductivity. The feasibility of the device is here discussed in view of the final application. Thanks to the potential of atomic magnetometers for miniaturisation and extreme sensitivity at room temperature, a new generation of compact and non-invasive diagnostic instrumentation, with both bedside and intra-operative operation capability, is envisioned. Possible scenarios both in clinical practice and biomedical research are then discussed. The flexibility of the system makes it promising also for application in other fields, such as neurology and oncology.
Protein single-model quality assessment by feature-based probability density functions
Authors: Cao Renzhi , Cheng Jianlin 
Published: April 2016

AbstractProtein quality assessment (QA) has played an important role in protein structure prediction. We developed a novel single-model quality assessment method–Qprob. Qprob calculates the absolute error for each protein feature value against the true quality scores (i.e. GDT-TS scores) of protein structural models and uses them to estimate its probability density distribution for quality assessment. Qprob has been blindly tested on the 11th Critical Assessment of Techniques for Protein Structure Prediction (CASP11) as MULTICOM-NOVEL server. The official CASP result shows that Qprob ranks as one of the top single-model QA methods. In addition, Qprob makes contributions to our protein tertiary structure predictor MULTICOM, which is officially ranked 3rd out of 143 predictors. The good performance shows that Qprob is good at assessing the quality of models of hard targets. These results demonstrate that this new probability density distribution based method is effective for protein single-model quality assessment and is useful for protein structure prediction. The webserver of Qprob is available at: http://calla.rnet.missouri.edu/qprob/. The software is now freely available in the web server of Qprob.
Finding Communities by Their Centers
Authors: Chen Yan , Zhao Pei , Li Ping , Zhang Kai , Zhang Jie 
Published: April 2016

AbstractDetecting communities or clusters in a real-world, networked system is of considerable interest in various fields such as sociology, biology, physics, engineering science, and interdisciplinary subjects, with significant efforts devoted in recent years. Many existing algorithms are only designed to identify the composition of communities, but not the structures. Whereas we believe that the local structures of communities can also shed important light on their detection. In this work, we develop a simple yet effective approach that simultaneously uncovers communities and their centers. The idea is based on the premise that organization of a community generally can be viewed as a high-density node surrounded by neighbors with lower densities, and community centers reside far apart from each other. We propose so-called “community centrality” to quantify likelihood of a node being the community centers in such a landscape, and then propagate multiple, significant center likelihood throughout the network via a diffusion process. Our approach is an efficient linear algorithm, and has demonstrated superior performance on a wide spectrum of synthetic and real world networks especially those with sparse connections amongst the community centers.