bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bridge helix bending promotes RNA polymerase II backtracking through a critical and conserved threonine residue
Authors: Da Lin-Tai , Pardo-Avila Fátima , Xu Liang , Silva Daniel-Adriano , Zhang Lu , Gao Xin , Wang Dong , Huang Xuhui 
Published: April 2016

AbstractThe dynamics of the RNA polymerase II (Pol II) backtracking process is poorly understood. We built a Markov State Model from extensive molecular dynamics simulations to identify metastable intermediate states and the dynamics of backtracking at atomistic detail. Our results reveal that Pol II backtracking occurs in a stepwise mode where two intermediate states are involved. We find that the continuous bending motion of the Bridge helix (BH) serves as a critical checkpoint, using the highly conserved BH residue T831 as a sensing probe for the 3′-terminal base paring of RNA:DNA hybrid. If the base pair is mismatched, BH bending can promote the RNA 3′-end nucleotide into a frayed state that further leads to the backtracked state. These computational observations are validated by site-directed mutagenesis and transcript cleavage assays, and provide insights into the key factors that regulate the preferences of the backward translocation.
Atomic mechanism of polarization-controlled surface reconstruction in ferroelectric thin films
Authors: Gao Peng , Liu Heng-Jui , Huang Yen-Lin , Chu Ying-Hao , Ishikawa Ryo , Feng Bin , Jiang Ying , Shibata Naoya , Wang En-Ge , Ikuhara Yuichi 
Published: April 2016

AbstractAt the ferroelectric surface, the broken translational symmetry induced bound charge should significantly alter the local atomic configurations. Experimentally revealing the atomic structure of ferroelectric surface, however, is very challenging due to the strong spatial variety between nano-sized domains, and strong interactions between the polarization and other structural parameters. Here, we study surface structures of Pb(Zr0.2Ti0.8)O3 thin film by using the annular bright-field imaging. We find that six atomic layers with suppressed polarization and a charged 180° domain wall are at negatively poled surfaces, no reconstruction exists at positively poled surfaces, and seven atomic layers with suppressed polarization and a charged 90° domain wall exist at nominally neutral surfaces in ferroelastic domains. Our results provide critical insights into engineering ferroelectric thin films, fine grain ceramics and surface chemistry devices. The state-of-the-art methodology demonstrated here can greatly advance our understanding of surface science for oxides.
Exploring the biophysical option space for feeding the world without deforestation
Authors: Erb Karl-Heinz , Lauk Christian , Kastner Thomas , Mayer Andreas , Theurl Michaela C. , Haberl Helmut 
Published: April 2016

AbstractSafeguarding the world’s remaining forests is a high-priority goal. We assess the biophysical option space for feeding the world in 2050 in a hypothetical zero-deforestation world. We systematically combine realistic assumptions on future yields, agricultural areas, livestock feed and human diets. For each scenario, we determine whether the supply of crop products meets the demand and whether the grazing intensity stays within plausible limits. We find that many options exist to meet the global food supply in 2050 without deforestation, even at low crop-yield levels. Within the option space, individual scenarios differ greatly in terms of biomass harvest, cropland demand and grazing intensity, depending primarily on the quantitative and qualitative aspects of human diets. Grazing constraints strongly limit the option space. Without the option to encroach into natural or semi-natural land, trade volumes will rise in scenarios with globally converging diets, thereby decreasing the food self-sufficiency of many developing regions.
Aurora A drives early signalling and vesicle dynamics during T-cell activation
Authors: Blas-Rus Noelia , Bustos-Morán Eugenio , Pérez de Castro Ignacio , de Cárcer Guillermo , Borroto Aldo , Camafeita Emilio , Jorge Inmaculada , Vázquez Jesús , Alarcón Balbino , Malumbres Marcos , Martín-Cófreces Noa B. , Sánchez-Madrid Francisco 
Published: April 2016

AbstractAurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal.
The effects of a low-energy, high frequency liquid optic interface femtosecond laser system on lens capsulotomy
Authors: Williams Geraint P. , George Ben L. , Wong Yoke R. , Seah Xin-Yi , Ang Heng-Pei , Loke Mun Kitt A. , Tay Shian Chao , Mehta Jod S. 
Published: April 2016

AbstractThe introduction of femtosecond laser assisted cataract surgery (FLACS) is a paradigm changing approach in cataract surgery, the most commonly performed surgical procedure. FLACS has the potential to optimize the creation of an anterior lens capsulotomy, a critical step in accessing the cataractous lens. The merits of using a laser instead of a manual approach include a potentially more circular, consistent and stronger aperture. In this study we demonstrated for the first time in both a porcine and human experimental setting that with a low energy, high repetition FLACS system, that a circular, smooth and strong capsulotomy was achievable. While there was no demonstrable difference in the resistance to rupture before or after the removal of the nucleus, larger capsulotomies had an increase in tensile strength. The LDV Z8 system appeared to create circular, rupture-resistant and smooth capsulotomies in both porcine and more importantly human globes.
Oscillatory penetration of near-fields in plasmonic excitation at metal-dielectric interfaces
Authors: Lee S. C. , Kang J. H. , Park Q-H. , Krishna S. , Brueck S. R. J. 
Published: April 2016

AbstractThe electric field immediately below an illuminated metal-film that is perforated with a hole array on a dielectric consists of direct transmission and scattering of the incident light through the holes and evanescent near-field from plasmonic excitations. Depending on the size and shape of the hole apertures, it exhibits an oscillatory decay in the propagation direction. This unusual field penetration is explained by the interference between these contributions, and is experimentally confirmed through an aperture which is engineered with four arms stretched out from a simple circle to manipulate a specific plasmonic excitation available in the metal film. A numerical simulation quantitatively supports the experiment. This fundamental characteristic will impact plasmonics with the near-fields designed by aperture engineering for practical applications.
Oncolytic Activity of a Recombinant Measles Virus, Blind to Signaling Lymphocyte Activation Molecule, Against Colorectal Cancer Cells
Authors: Amagai Yosuke , Fujiyuki Tomoko , Yoneda Misako , Shoji Koichiro , Furukawa Yoichi , Sato Hiroki , Kai Chieko 
Published: April 2016

AbstractOncolytic virotherapy is a distinctive antitumor therapy based on the cancer-cell-specific infectivity and killing activity of viruses, which exert a considerable antitumor effect with only a few treatments. Because colorectal cancer cells often acquire resistance to the molecular-targeted therapies and alternative treatments are called for, in this study, we evaluated the oncolytic activity against colorectal cancer cells of a recombinant measles virus (rMV-SLAMblind), which is blind to signaling lymphocytic activation molecule (SLAM) and infects target cells via nectin-4/poliovirus receptor-related 4 protein. We examined 10 cell lines including 8 cell lines that were resistant to epidermal-growth-factor-receptor (EGFR) targeted therapy. rMV-SLAMblind infected and lysed the nectin-4-positive cell lines dependently on nectin-4 expression, in spite of mutation in EGFR cascade. Tumour progression in xenograft models was also abrogated by the virus and the infection of cancer cells in vivo by the virus was demonstrated with both flow cytometry and a histological analysis. Therefore, rMV-SLAMblind is considered a novel therapeutic agent for colorectal cancers, including those resistant to molecular-targeted therapies.
Angle-dependent magnetotransport in GaAs/InAs core/shell nanowires
Authors: Haas Fabian , Wenz Tobias , Zellekens Patrick , Demarina Nataliya , Rieger Torsten , Lepsa Mihail , Grützmacher Detlev , Lüth Hans , Schäpers Thomas 
Published: April 2016

AbstractWe study the impact of the direction of magnetic flux on the electron motion in GaAs/InAs core/shell nanowires. At small tilt angles, when the magnetic field is aligned nearly parallel to the nanowire axis, we observe Aharonov–Bohm type h/e flux periodic magnetoconductance oscillations. These are attributed to transport via angular momentum states, formed by electron waves within the InAs shell. With increasing tilt of the nanowire in the magnetic field, the flux periodic magnetoconductance oscillations disappear. Universal conductance fluctuations are observed for all tilt angles, however with increasing amplitudes for large tilt angles. We record this evolution of the electron propagation from a circling motion around the core to a diffusive transport through scattering loops and give explanations for the observed different transport regimes separated by the magnetic field orientation.
Femtomagnetism in graphene induced by core level excitation of organic adsorbates
Authors: Ravikumar Abhilash , Baby Anu , Lin He , Brivio Gian Paolo , Fratesi Guido 
Published: April 2016

AbstractWe predict the induction or suppression of magnetism in the valence shell of physisorbed and chemisorbed organic molecules on graphene occurring on the femtosecond time scale as a result of core level excitations. For physisorbed molecules, where the interaction with graphene is dominated by van der Waals forces and the system is non-magnetic in the ground state, numerical simulations based on density functional theory show that the valence electrons relax towards a spin polarized configuration upon excitation of a core-level electron. The magnetism depends on efficient electron transfer from graphene on the femtosecond time scale. On the other hand, when graphene is covalently functionalized, the system is magnetic in the ground state showing two spin dependent mid gap states localized around the adsorption site. At variance with the physisorbed case upon core-level excitation, the LUMO of the molecule and the mid gap states of graphene hybridize and the relaxed valence shell is not magnetic anymore.
Sports Activity after Low-contact-stress Total Knee Arthroplasty – A long term follow-up study
Authors: Vielgut Ines , Leitner Lukas , Kastner Norbert , Radl Roman , Leithner Andreas , Sadoghi Patrick 
Published: April 2016

AbstractThe purpose of this study was to provide comprehensive long-term data about sports activity levels in patients following total knee arthroplasty (TKA) and to determine the impact of pre-operative function, pain and specific performed sports on the results. 236 patients who have undergone TKA for severe osteoarthritis of the knee were asked to provide specific information regarding exercised types of sports before surgery and after at least 10 years following TKA. Pre- and postoperative function and pain were evaluated by the use of Tegner-, WOMAC- and VAS Score. After a mean of 14.9 years, a significant improvement regarding pain and function was observed. Pre-operative Tegner- and WOMAC scores revealed significant positive correlations with the post-operative Tegner-Score. Accordingly, a high percentage of patients (70.9%) stayed actively involved in sports. Nevertheless, the number of performing patients has decreased according to the sports impact. 71.3% continued practising low-impact-, 43.7% intermediate-impact sports whereas only 16.4% kept performing high impact sports. We conclude that TKA is highly effective in long-time pain reduction as well as improvement of function. Additionally, we found considerable sports activities preserved in the investigated series. However, sports activities in particular, seem to decrease according to the impact of sports.
Erythroleukemia cells acquire an alternative mitophagy capability
Authors: Wang Jian , Fang Yixuan , Yan Lili , Yuan Na , Zhang Suping , Xu Li , Nie Meilan , Zhang Xiaoying , Wang Jianrong 
Published: April 2016

AbstractLeukemia cells are superior to hematopoietic cells with a normal differentiation potential in buffering cellular stresses, but the underlying mechanisms for this leukemic advantage are not fully understood. Using CRISPR/Cas9 deletion of the canonical autophagy-essential gene Atg7, we found that erythroleukemia K562 cells are armed with two sets of autophagic machinery. Alternative mitophagy is functional regardless of whether the canonical autophagic mechanism is intact or disrupted. Although canonical autophagy defects attenuated cell cycling, proliferation and differentiation potential, the leukemia cells retained their abilities for mitochondrial clearance and for maintaining low levels of reactive oxygen species (ROS) and apoptosis. Treatment with a specific inducer of mitophagy revealed that the canonical autophagy-defective erythroleukemia cells preserved a mitophagic response. Selective induction of mitophagy was associated with the upregulation and localization of RAB9A on the mitochondrial membrane in both wild-type and Atg7−/− leukemia cells. When the leukemia cells were treated with the alternative autophagy inhibitor brefeldin A or when the RAB9A was knocked down, this mitophagy was prohibited. This was accompanied by elevated ROS levels and apoptosis as well as reduced DNA damage repair. Therefore, the results suggest that erythroleukemia K562 cells possess an ATG7-independent alternative mitophagic mechanism that functions even when the canonical autophagic process is impaired, thereby maintaining the ability to respond to stresses such as excessive ROS and DNA damage.
Transient activation of human cytomegalovirus lytic gene expression during latency allows cytotoxic T cell killing of latently infected cells
Authors: Krishna B. A. , Lau B. , Jackson S. E. , Wills M. R. , Sinclair J. H. , Poole E. 
Published: April 2016

AbstractHuman cytomegalovirus (HCMV) latency in the myeloid lineage is maintained by repressive histone modifications around the major immediate early promoter (MIEP), which results in inhibition of the lytic viral life cycle. We now show that pharmacological inhibition of histone deacetylases (HDACs) relieves this repression of the MIEP and induces transient expression of the viral lytic immediate early (IE) antigens but, importantly, not full virus reactivation. In turn, these latently infected cells now become targets for IE-specific cytotoxic T cells (CTLs) which are present at high frequency in all normal healthy HCMV positive carriers but would normally be unable to target latent (lytic antigen-negative) cells. This approach of transiently inducing viral lytic gene expression by HDAC inhibition, in otherwise latently infected cells, offers a window of opportunity to target and purge the latent myeloid cell reservoir by making these normally immunologically undetectable cells visible to pre-existing host immune responses to viral lytic antigens.
A reliable Raman-spectroscopy-based approach for diagnosis, classification and follow-up of B-cell acute lymphoblastic leukemia
Authors: Managò Stefano , Valente Carmen , Mirabelli Peppino , Circolo Diego , Basile Filomena , Corda Daniela , De Luca Anna Chiara 
Published: April 2016

AbstractAcute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder that shows high mortality rates due to immature lymphocyte B-cell proliferation. B-ALL diagnosis requires identification and classification of the leukemia cells. Here, we demonstrate the use of Raman spectroscopy to discriminate normal lymphocytic B-cells from three different B-leukemia transformed cell lines (i.e., RS4;11, REH, MN60 cells) based on their biochemical features. In combination with immunofluorescence and Western blotting, we show that these Raman markers reflect the relative changes in the potential biological markers from cell surface antigens, cytoplasmic proteins and DNA content and correlate with the lymphoblastic B-cell maturation/differentiation stages. Our study demonstrates the potential of this technique for classification of B-leukemia cells into the different differentiation/maturation stages, as well as for the identification of key biochemical changes under chemotherapeutic treatments. Finally, preliminary results from clinical samples indicate high consistency of and potential applications for, this Raman spectroscopy approach.
Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury
Authors: Roy Sanchari , Benz Fabian , Alder Jan , Bantel Heike , Janssen Joern , Vucur Mihael , Gautheron Jeremie , Schneider Anne , Schüller Florian , Loosen Sven , Luedde Mark , Koch Alexander , Tacke Frank , Luedde Tom , Trautwein Christian , Roderburg Christoph 
Published: April 2016

miR-192-5p has gained increasing relevance in various diseases, however, its function in acute liver injury is currently unknown. We analysed miR-192-5p serum levels and hepatic miR-192-5p expression in mice after hepatic ischaemia and reperfusion (I/R) as well as in toxic liver injury. On a functional level, miRNA levels were analysed in the different hepatic cell-compartments and in the context of tumour necrosis factor (TNF)-dependent liver cell death. We detected increased serum levels of miR-192-5p after hepatic I/R- and carbon tetrachloride (CCl4)-induced liver injury. miR-192-5p levels correlated with the degree of liver damage and the presence of hepatic cell death detected by TUNEL stainings (terminal deoxynucleotidyltransferase-mediated dUTP biotin nick-end labelling stainings). Moreover, expression of miR-192-5p was increased in a hypoxia/reoxygenation (H/R) model of in vitro hepatocyte injury, supporting that the passive release of miR-192-5p represents a surrogate for hepatocyte death in liver injury. In critically ill patients, miR-192-5p levels were elevated selectively in patients with liver injury and closely correlated with the presence of hepatic injury. In contrast with up-regulated miR-192-5p in the serum, we detected a down-regulation of miR-192-5p in both injured mouse and human livers. Deregulation of miR-192-5p in livers was dependent on stimulation with TNF. Functional experiments confirmed a protective effect of down-regulation of miR-192-5p in hepatocytes, suggesting a role of miR-192-5p in limiting liver injury. Finally, we identified Zeb2, an important regulator of cell death, as a potential target gene mediating the function of miR-192-5p. Our data suggest that miR-192-5p is involved in the regulation of liver cell death during acute liver injury and might represent a potent marker of hepatic injury.
Sex differences in the circadian regulation of sleep and waking cognition in humans
Authors: Santhi Nayantara , Lazar Alpar S. , McCabe Patrick J. , Lo June C. , Groeger John A. , Dijk Derk-Jan 
Published: April 2016

Significance
Circadian rhythms affect our physiology and psychology, in health and disease. Most of our knowledge about the human circadian timing system is based on research in men. Some circadian characteristics, such as the intrinsic frequency of the circadian clock and the amplitude of the melatonin rhythm, have been shown to differ between men and women. Whether the circadian regulation of mental functions differs between men and women is unknown. Here we show that circadian rhythmicity in mental functions exhibits sex differences so that the night-time impairment in cognitive performance is greater in women than in men. These findings are significant in view of shift-work–related cognitive deficits and disturbances of mood, which are more prevalent in women.
Gelada vocal sequences follow Menzerath’s linguistic law
Authors: Gustison Morgan L. , Semple Stuart , Ferrer-i-Cancho Ramon , Bergman Thore J. 
Published: April 2016

SignificanceHuman language follows a variety of structural principles, known as linguistic laws. One of these, Menzerath’s law, states that, the larger the size of the construct (e.g., the size of a word in terms of syllable number), the smaller the size of the individual constituent parts (e.g., syllables). We show for the first time (to our knowledge) that Menzerath’s law also holds in the vocal communication of a nonhuman species. In the gelada (Theropithecus gelada), a primate living in the highlands of Ethiopia, longer vocal sequences produced by adult males were associated with shorter individual calls. This result suggests that general—perhaps universal—principles underpin the structure of vocal communication in our own species and others.
Phosphorylation of synaptotagmin-1 controls a post-priming step in PKC-dependent presynaptic plasticity
Authors: de Jong Arthur P. H. , Meijer Marieke , Saarloos Ingrid , Cornelisse Lennart Niels , Toonen Ruud F. G. , Sørensen Jakob B. , Verhage Matthijs 
Published: April 2016

Significance
Synapses can be temporarily strengthened by bursts of action potentials, which are thought to be a central aspect of information processing in the brain. This study provides evidence that protein kinase C (PKC)-dependent phosphorylation of synaptotagmin-1 is an essential step in this strengthening. A mutation that prevents synaptotagmin-1 phosphorylation abolishes this strengthening, both after action potential bursts and upon direct PKC activation by a synthetic analog of diacylglycerol, whereas basal synaptic transmission is unaffected. This suggests that synaptotagmin-1 acts in a cooperative fashion with Munc18-1 and Munc13-1, which were previously identified as essential diacylglycerol/PKC substrates. Together these data identify a central pathway linking bursts of action potentials to enhanced synaptic strength.
Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3
Authors: Liang Wenguang G. , Triandafillou Catherine G. , Huang Teng-Yi , Zulueta Medel Manuel L. , Banerjee Shiladitya , Dinner Aaron R. , Hung Shang-Cheng , Tang Wei-Jen 
Published: April 2016

SignificanceOligomerization and glycosaminoglycan (GAG) binding are key regulatory steps for many extracellular ligands. Our analyses provide a structural basis of CC chemokine ligand 5 (CCL5) and CCL3 oligomerization and explain how oligomerization affects the interaction of these chemokines with GAG and their functions. Our GAG-bound chemokine structures reveal how CCL5 and CCL3 oligomerization creates distinctive GAG-binding grooves to enhance GAG binding via avidity for regulating chemokine functions. Furthermore, our CCL5 structure may explain how CXCL4, a CXC chemokine, heterooligomerizes with CCL5 to modulate chemokine-mediated activities. Together, these data provide new structural insights into how oligomerization and GAG binding are coupled to regulate functions of CC chemokines and offer novel pharmacophores for the design of therapeutics for treating chemokine-mediated human diseases.