bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective recognition and stabilization of new ligands targeting the potassium form of the human telomeric G-quadruplex DNA
Authors: Lin Yi-Hwa , Chuang Show-Mei , Wu Pei-Ching , Chen Chun-Liang , Jeyachandran Sivakamavalli , Lo Shou-Chen , Huang Hsu-Shan , Hou Ming-Hon 
Published: August 2016

AbstractThe development of a ligand that is capable of distinguishing among the wide variety of G-quadruplex structures and targeting telomeres to treat cancer is particularly challenging. In this study, the ability of two anthraquinone telomerase inhibitors (NSC749235 and NSC764638) to target telomeric G-quadruplex DNA was probed. We found that these ligands specifically target the potassium form of telomeric G-quadruplex DNA over the DNA counterpart. The characteristic interaction with the telomeric G-quadruplex DNA and the anticancer activities of these ligands were also explored. The results of this present work emphasize our understanding of the binding selectivity of anthraquinone derivatives to G-quadruplex DNA and assists in future drug development for G-quadruplex-specific ligands.
Predicting bee community responses to land-use changes: Effects of geographic and taxonomic biases
Authors: De Palma Adriana , Abrahamczyk Stefan , Aizen Marcelo A. , Albrecht Matthias , Basset Yves , Bates Adam , Blake Robin J. , Boutin Céline , Bugter Rob , Connop Stuart , Cruz-López Leopoldo , Cunningham Saul A. , Darvill Ben , Diekötter Tim , Dorn Silvia , Downing Nicola , Entling Martin H. , Farwig Nina , Felicioli Antonio , Fonte Steven J. , Fowler Robert , Franzén Markus , Goulson Dave , Grass Ingo , Hanley Mick E. , Hendrix Stephen D. , Herrmann Farina , Herzog Felix , Holzschuh Andrea , Jauker Birgit , Kessler Michael , Knight M. E. , Kruess Andreas , Lavelle Patrick , Le Féon Violette , Lentini Pia , Malone Louise A. , Marshall Jon , Pachón Eliana Martínez , McFrederick Quinn S. , Morales Carolina L. , Mudri-Stojnic Sonja , Nates-Parra Guiomar , Nilsson Sven G. , Öckinger Erik , Osgathorpe Lynne , Parra-H Alejandro , Peres Carlos A. , Persson Anna S. , Petanidou Theodora , Poveda Katja , Power Eileen F. , Quaranta Marino , Quintero Carolina , Rader Romina , Richards Miriam H. , Roulston T’ai , Rousseau Laurent , Sadler Jonathan P. , Samnegård Ulrika , Schellhorn Nancy A. , Schüepp Christof , Schweiger Oliver , Smith-Pardo Allan H. , Steffan-Dewenter Ingolf , Stout Jane C. , Tonietto Rebecca K. , Tscharntke Teja , Tylianakis Jason M. , Verboven Hans A. F. , Vergara Carlos H. , Verhulst Jort , Westphal Catrin , Yoon Hyung Joo , Purvis Andy 
Published: August 2016

AbstractLand-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises.
Reinstating the Novelty P3
Authors: Barry Robert J. , Steiner Genevieve Z. , De Blasio Frances M. 
Published: August 2016

AbstractP300 (or P3) is a major positive complex in the human event-related potential, occurring some 300 ms after stimulus onset and long thought to be the cortical correlate of the Orienting Reflex, our automatic attention-grabbing response to a novel stimulus. The Novelty P3 was the third P3 subcomponent discovered (after P3a and P3b) and appeared promising in its sensitivity to stimulus novelty, the defining characteristic of the Orienting Reflex. But some 15 years later it was claimed to be indistinguishable from the previously-discovered P3a. This led to a decline in interest in the field and confused nomenclature, with some studies using “P3a” and “Novelty P3” interchangeably. However, recent similar studies have again reported three subcomponents of the P3. Further, using single-stimulus habituation paradigms, in addition to P3a and P3b, a later decrementing P3 subcomponent has been reported and recently labelled “HabP3” to avoid contention. We report three studies to resolve this chaotic situation, arguing for identification of the late subcomponent following the P3a and P3b as the Novelty P3. Reinstatement of the Novelty P3 as the central index of the Orienting Reflex will have widespread impact in a range of theoretical, practical and clinical areas involving novelty processing and attention.
Controllably Alloyed, Low Density, Free-standing Ni-Co and Ni-Graphene Sponges for Electrocatalytic Water Splitting
Authors: Vineesh Thazhe Veettil , Mubarak Suhail , Hahm Myung Gwan , Prabu V. , Alwarappan Subbiah , Narayanan Tharangattu N. 
Published: August 2016

AbstractSynthesis of low cost, durable and efficient electrocatalysts that support oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are the bottlenecks in water electrolysis. Here we propose a strategy for the development of controllably alloyed, porous, and low density nickel (Ni) and cobalt (Co) based alloys - whose electrocatalytic properties can be tuned to make them multifunctional. Ni and Co based alloy with the chemical structure of Ni1Co2is identified as an efficient OER catalyst among other stoichiometric structures in terms of over potential @ 10 mAcm−2(1.629 V), stability, low tafel slope (87.3 mV/dec), and high Faradaic efficiency (92%), and its OER performance is also found to be on par with the benchmarked IrO2. Tunability in the porous metal synthesis strategy allowed the incorporation of graphene during the Ni sponge formation, and the Ni- incorporated nitrogen doped graphene sponge (Ni-NG) is found to have very high HER activity. A water electrolysis cell fabricated and demonstrated with these freestanding electrodes is found to have high stability (>10 hours) and large current density (10 mAcm−2@ 1.6 V), opening new avenues in the design and development of cost effective and light weight energy devices.
Enzyme overexpression – an exercise toward understanding regulation of heparan sulfate biosynthesis
Authors: Fang Jianping , Song Tianyi , Lindahl Ulf , Li Jin-Ping 
Published: August 2016

AbstractBiosynthesis of heparan sulfate (HS) involves conversion of D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) units catalyzed by glucuronyl C5-epimerase (Hsepi). IdoA units are the favored substrate for 2-O-sulfotransferase (2OST). We used HEK293 cells as a model to investigate the effects of overexpression of these enzymes on HS structure. Overexpression of Hsepi alone resulted in an unexpected increase in HS chain length. A Hsepi point-mutant (Y168A), devoid of catalytic activity, failed to affect chain length. Moreover, the effect of Hsepi overexpression on HS chain length was abolished by simultaneous overexpression of 2OST. These findings raise novel aspects on regulation of HS biosynthesis. We propose a hypothetical enzyme-binding protein (EBP) with distinct, specific and partly overlapping binding sites, the interactions of which will determine levels of enzymes available to the biosynthetic process.
Porous V2O5/RGO/CNT hierarchical architecture as a cathode material: Emphasis on the contribution of surface lithium storage
Authors: Palanisamy Kowsalya , Um Ji Hyun , Jeong Mihee , Yoon Won-Sub 
Published: August 2016

AbstractA three dimensional vanadium pentoxide/reduced graphene oxide/carbon nanotube (3D V2O5/RGO/CNT) composite is synthesized by microwave-assisted hydrothermal method. The combination of 2D RGO and 1D CNT establishes continuous 3D conductive network and most notably, the 1D CNT is designed to form hierarchically porous structure by penetrating into V2O5 microsphere assembly constituted of numerous V2O5 nanoparticles. The highly porous V2O5 microsphere enhances electrolyte contact and shortens Li+ diffusion path as a consequence of its developed surface area and mesoporosity. The successive phase transformations of 3D V2O5/RGO/CNT from α-phase to ε-, δ-, γ- and ω-phase and its structural reversibility upon Li+ intercalation/de-intercalation are investigated by in situ XRD analysis and the electronic and local structure reversibility around vanadium atom in 3D V2O5/RGO/CNT is observed by in situ XANES analysis. The 3D V2O5/RGO/CNT achieves a high capacity of 220 mAh g−1 at 1 C after 80 cycles and an excellent rate capability of 100 mAh g−1 even at a considerably high rate of 20 C. The porous 3D V2O5/RGO/CNT structure not only provides facile Li+ diffusion into bulk but contributes to surface Li+ storage as well, which enables the design of 3D V2O5/RGO/CNT composite to become a promising cathode architecture for high performance LIBs.
CircRNA-protein complexes: IMP3 protein component defines subfamily of circRNPs
Authors: Schneider Tim , Hung Lee-Hsueh , Schreiner Silke , Starke Stefan , Eckhof Heinrich , Rossbach Oliver , Reich Stefan , Medenbach Jan , Bindereif Albrecht 
Published: August 2016

AbstractCircular RNAs (circRNAs) constitute a new class of noncoding RNAs in higher eukaryotes generated from pre-mRNAs by alternative splicing. Here we investigated in mammalian cells the association of circRNAs with proteins. Using glycerol gradient centrifugation, we characterized in cell lysates circRNA-protein complexes (circRNPs) of distinct sizes. By polysome-gradient fractionation we found no evidence for efficient translation of a set of abundant circRNAs in HeLa cells. To identify circRNPs with a specific protein component, we focused on IMP3 (IGF2BP3, insulin-like growth factor 2 binding protein 3), a known tumor marker and RNA-binding protein. Combining RNA-seq analysis of IMP3-co-immunoprecipitated RNA and filtering for circular-junction reads identified a set of IMP3-associated circRNAs, which were validated and characterized. In sum, our data suggest that specific circRNP families exist defined by a common protein component. In addition, this provides a general approach to identify circRNPs with a given protein component.
Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials
Authors: Radivojevic Milos , Jäckel David , Altermatt Michael , Müller Jan , Viswam Vijay , Hierlemann Andreas , Bakkum Douglas J. 
Published: August 2016

AbstractA detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs.
Copy number variation of genes involved in the hepatitis C virus-human interactome
Authors: Budzko Lucyna , Marcinkowska-Swojak Malgorzata , Jackowiak Paulina , Kozlowski Piotr , Figlerowicz Marek 
Published: August 2016

AbstractCopy number variation (CNV) is a newly discovered form of intra-species genetic polymorphism that is defined as deletions or duplications of genome segments ranging from 1 kbp to several Mbp. CNV accounts for the majority of the genetic variation observed in humans (CNV regions cover more than 10% of the human genome); therefore, it may significantly influence both the phenotype and susceptibility to various diseases. Unfortunately, the impact of CNV on a number of diseases, including hepatitis C virus (HCV) infection, remains largely unexplored. Here, we analyzed 421 human genes encoding proteins that have been shown to interact with HCV proteins or genomic RNA (proteins from the HCV-human interactome). We found that 19 of the 421 candidate genes are located in putative CNV regions. For all of these genes, copy numbers were determined for European, Asiatic and African populations using the multiplex ligation-dependent amplification (MLPA) method. As a result, we identified 4 genes, IGLL1, MLLT4, PDPK1, PPP1R13L, for which the CN-genotype ranged from 1 to 6. All of these genes are involved in host-virus interaction; thus, their polymorphism has a potential impact on the development of HCV infection and/or therapy outcome.
A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains
Authors: Mairpady Shambat Srikanth , Siemens Nikolai , Monk Ian R. , Mohan Disha B. , Mukundan Santhosh , Krishnan Karthickeyan Chella , Prabhakara Sushma , Snäll Johanna , Kearns Angela , Vandenesch Francois , Svensson Mattias , Kotb Malak , Gopal Balasubramanian , Arakere Gayathri , Norrby-Teglund Anna 
Published: August 2016

AbstractMethicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and soft tissue infections. One of the highly successful and rapidly disseminating clones is MRSA ST22 commonly associated with skin tropism. Here we show that a naturally occurring single amino acid substitution (tyrosine to cysteine) at position 223 of AgrC determines starkly different ST22 S. aureus virulence phenotypes, e.g. cytotoxic or colonizing, as evident in both in vitro and in vivo skin infections. Y223C amino acid substitution destabilizes AgrC-AgrA interaction leading to a colonizing phenotype characterized by upregulation of bacterial surface proteins. The colonizing phenotype strains cause less severe skin tissue damage, show decreased susceptibility towards the antimicrobial LL-37 and induce autophagy. In contrast, cytotoxic strains with tyrosine at position 223 of AgrC cause infections characterized by inflammasome activation and severe skin tissue pathology. Taken together, the study demonstrates how a single amino acid substitution in the histidine kinase receptor AgrC of ST22 strains determines virulence properties and infection outcome.
U6atac snRNA stem-loop interacts with U12 p65 RNA binding protein and is functionally interchangeable with the U12 apical stem-loop III
Authors: Singh Jagjit , Sikand Kavleen , Conrad Heike , Will Cindy L. , Komar Anton A. , Shukla Girish C. 
Published: August 2016

AbstractFormation of catalytic core of the U12-dependent spliceosome involves U6atac and U12 interaction with the 5′ splice site and branch site regions of a U12-dependent intron, respectively. Beyond the formation of intermolecular helix I region between U6atac and U12 snRNAs, several other regions within these RNA molecules are predicted to form stem-loop structures. Our previous work demonstrated that the 3′ stem-loop region of U6atac snRNA contains a U12-dependent spliceosome-specific targeting activity. Here, we show a detailed structure-function analysis and requirement of a substructure of U6atac 3′ stem-loop in U12-dependent in vivo splicing. We show that the C-terminal RNA recognition motif of p65, a U12 snRNA binding protein, also binds to the distal 3′ stem-loop of U6atac. By using a binary splice site mutation suppressor assay we demonstrate that p65 protein-binding apical stem-loop of U12 snRNA can be replaced by this U6atac distal 3′ stem-loop. Furthermore, we tested the compatibility of the U6atac 3′ end from phylogenetically distant species in a human U6atac background, to establish the evolutionary relatedness of these structures and in vivo function. In summary, we demonstrate that RNA-RNA and RNA-protein interactions in the minor spliceosome are highly plastic as compared to the major spliceosome.
Pinch-off of microfluidic droplets with oscillatory velocity of inner phase flow
Authors: Zhu Pingan , Tang Xin , Tian Ye , Wang Liqiu 
Published: August 2016

AbstractWhen one liquid is introduced into another immiscible one, it ultimately fragments due to hydrodynamic instability. In contrast to neck pinch-off without external actuation, the viscous two-fluid system subjected to an oscillatory flow demonstrates higher efficiency in breaking fluid threads. However, the underlying dynamics of this process is less well understood. Here we show that the neck-thinning rate is accelerated by the amplitude of oscillation. By simply evaluating the momentum transfer from external actuation, we derive a dimensionless pre-factor to quantify the accelerated pinch-off. Our data ascribes the acceleration to the non-negligible inner fluid inertia, which neutralizes the inner phase viscous stress that retards the pinch-off. Moreover, we characterize an equivalent neck-thinning behavior between an actuated system and its unactuated counterpart with decreased viscosity ratio. Finally, we demonstrate that oscillation is capable of modulating satellite droplet formation by shifting the pinch-off location. Our study would be useful for manipulating fluids at microscale by external forcing.
The initial break-up of Pangæa elicited by Late Palæozoic deglaciation
Authors: Yeh Meng-Wan , Shellnutt J. Gregory 
Published: August 2016

AbstractThe break-up of Pangæa was principally facilitated by tensional plate stress acting on pre-existing suture zones. The rifting of Pangæa began during the Early Permian along the southern Tethys margin and produced the lenticular-shaped continent known as Cimmeria. A mantle-plume model is ascribed to explain the rift-related volcanism but the NW-SE oriented Cimmerian rifts do not correlate well with pre-existing suture zones or ‘structural heterogeneities’ but appear to have a pertinent spatial and temporal association with Late Palæozoic glacial-interglacial cycles. Mantle potential temperature estimates of Cimmerian rift-related basalts (1410 °C ± 50 °C) are similar to ambient mantle conditions rather than an active mantle-plume rift as previously suggested. Moreover, we find that the distribution of glacial deposits shows significant temporal and spatial concurrence between the glacial retreat margins and rifting sites. We conclude that the location and timing of Cimmerian rifting resulted from the exploitation of structural heterogeneities within the crust that formed due to repeated glacial-interglacial cycles during the Late Palæozoic. Such effects of continental deglaciation helped to create the lenticular shape of Cimmeria and Neotethys Ocean suggesting that, in some instances, climate change may directly influence the location of rifting.
Efficient liver repopulation of transplanted hepatocyte prevents cirrhosis in a rat model of hereditary tyrosinemia type I
Authors: Zhang Ludi , Shao Yanjiao , Li Lu , Tian Feng , Cen Jin , Chen Xiaotao , Hu Dan , Zhou Yan , Xie Weifen , Zheng Yunwen , Ji Yuan , Liu Mingyao , Li Dali , Hui Lijian 
Published: August 2016

AbstractHereditary tyrosinemia type I (HT1) is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (Fah). Fah-deficient mice and pigs are phenotypically analogous to human HT1, but do not recapitulate all the chronic features of the human disorder, especially liver fibrosis and cirrhosis. Rats as an important model organism for biomedical research have many advantages over other animal models. Genome engineering in rats is limited till the availability of new gene editing technologies. Using the recently developed CRISPR/Cas9 technique, we generated Fah−/− rats. The Fah−/− rats faithfully represented major phenotypic and biochemical manifestations of human HT1, including hypertyrosinemia, liver failure and renal tubular damage. More importantly, the Fah−/− rats developed remarkable liver fibrosis and cirrhosis, which have not been observed in Fah mutant mice or pigs. Transplantation of wild-type hepatocytes rescued the Fah−/− rats from impending death. Moreover, the highly efficient repopulation of hepatocytes in Fah−/− livers prevented the progression of liver fibrosis to cirrhosis and in turn restored liver architecture. These results indicate that Fah−/− rats may be used as an animal model of HT1 with liver cirrhosis. Furthermore, Fah−/− rats may be used as a tool in studying hepatocyte transplantation and a bioreactor for the expansion of hepatocytes.
Primary female breast sarcoma: clinicopathological features, treatment and prognosis
Authors: Yin Ming , Mackley Heath B. , Drabick Joseph J. , Harvey Harold A. 
Published: August 2016

AbstractPrimary breast sarcoma (PBS) is a rare and heterogeneous group of malignancies with limited publications. We obtained data from the Surveillance, Epidemiology, and End Results Program and performed analysis to determine clinicopathological characteristics of PBS and estimate their associations with overall survival (OS) and cancer-specific survival (CSS). Median age of PBS was 55–59 years and median OS was 108 months. Age, overlap or entire breast involvement, tumor histology, and tumor spread were associated with poor survival outcomes. In the multivariable analysis, tumor size, lymph node involvement, distant metastasis and histologic grade were correlated with survival outcomes (P < 0.001). In M0 patients, mastectomy was associated with worse survival outcomes compared with breast conservative surgery (BCS) (adjusted hazard ratio [adjHR], 1.80; 95% CI, 1.31–2.47), regardless of tumor size, tumor grade, tumor histology or radiation history. Adjuvant radiation improved survival outcomes in patients with tumor size >5 cm (adjHR, 0.63; 95% CI, 0.43–0.91), but not in patients with tumor size ≤ 5 cm. Our study demonstrated clinicopathological characteristics of PBS in the US population and supports performing BCS if R0 resection can be achieved, with radiation if tumor size is over 5 cm.