bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sanguisorba officinalis L synergistically enhanced 5-fluorouracil cytotoxicity in colorectal cancer cells by promoting a reactive oxygen species-mediated, mitochondria-caspase-dependent apoptotic pathway
Authors: Liu Meng-ping , Liao Min , Dai Cong , Chen Jie-feng , Yang Chun-juan , Liu Ming , Chen Zuan-guang , Yao Mei-cun 
Published: September 2016

AbstractSanguisorba officinalis L. radix is a widely used herb called DiYu (DY) in China and has an extensive range of bioactivities, including anti-cancer, anti-inflammatory, and anti-oxidative activities. However, there is little evidence to support its anti-cancer effects against colorectal cancer (CRC). The first-line chemotherapeutic agent 5-fluorouracil (5-FU) is used to treat CRC, but its efficiency is hampered by acquired drug resistance. This study found that a water extract of DY exerted anti-proliferative effects against two CRC cell lines (HCT-116 and RKO), and it sensitized CRC cells to 5-FU therapy by activating a reactive oxygen species (ROS)-mediated, mitochondria-caspase-dependent apoptotic pathway. Co-treatment of DY and 5-FU significantly elevated ROS levels, up-regulated Bax/Bcl-2 ratio and triggered mitochondrial dysfunction, followed by a release of cytochrome c and up-regulation of proteins such as cleaved-caspase-9/3 and cleaved-PARP. Additionally, the induction of autophagy may be involved in mediating synergism of DY in HCT-116 cells. Gallic acid (GA), catechinic acid (CA) and ellagic acid (EA) were identified as the potential chief constituents responsible for the synergistic effects of DY. In conclusion, co-treatment of DY, specifically GA, CA and EA, with 5-FU may be a potential alternative therapeutic strategy for CRC by enhancing an intrinsic apoptotic pathway.
Changes in disc status in the reducing and nonreducing anterior disc displacement of temporomandibular joint: a longitudinal retrospective study
Authors: Hu Ying Kai , Yang Chi , Xie Qian Yang 
Published: September 2016

AbstractTreatment procedures for anterior disc displacement (ADD) of temporomandibular joint (TMJ) are far from reaching a consensus. The aim of the study was to evaluate disc status changes of anterior disc displacement with reduction (ADDWR) and without reduction (ADDWoR) comparatively, to get a better understanding of the disease progress without intervention. This longitudinal retrospective study included 217 joints in 165 patients, which were divided into ADDWR group and ADDWoR group based on magnetic resonance imaging (MRI) examination. The joints were assessed quantitatively for disc length and displacement distance at initial and follow-up visits. Disc morphology, which was classified in 5 types, was also evaluated. Paired t-test and Wilcoxon signed rank test were used to assess intra-group differences and independent t-test for inter-group differences. Moreover, analysis of covariance was applied to analyze influential factors for changes in disc length and displacement distance. According to our results, discs tended to become shorter, move further forward and distort more seriously in ADDWoR group than in ADDWR group after follow-up. Moreover, discs were prone to become shorter and more anteriorly displaced in teenagers, type I and III morphologies, advanced Wilkes stages, or those with joint effusion. Follow-up period seemed to be not critical.
Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection
Authors: Bear Joseph C. , Patrick P. Stephen , Casson Alfred , Southern Paul , Lin Fang-Yu , Powell Michael J. , Pankhurst Quentin A. , Kalber Tammy , Lythgoe Mark , Parkin Ivan P. , Mayes Andrew G. 
Published: September 2016

AbstractDrug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it’s drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine.
Impact of the 2015 El Nino event on winter air quality in China
Authors: Chang Luyu , Xu Jianming , Tie Xuexi , Wu Jianbin 
Published: September 2016

AbstractDuring the winter of 2015, there was a strong El Nino (ENSO) event, resulting in significant anomalies for meteorological conditions in China. Analysis shows that the meteorological conditions in December 2015 (compared to December 2014) had several important anomalies, including the following: (1) the surface southeasterly winds were significantly enhanced in the North China Plain (NCP); (2) the precipitation was increased in the south of eastern China; and (3) the wind speeds were decreased in the middle-north of eastern China, while slightly increased in the south of eastern China. These meteorological anomalies produced important impacts on the aerosol pollution in eastern China. In the NCP region, the PM2.5 concentrations were significantly increased, with a maximum increase of 80–100 μg m−3. A global chemical/transport model (MOZART-4) was applied to study the individual contribution of the changes in winds and precipitation to PM2.5 concentrations. This study suggests that the 2015El Nino event had significant effects on air pollution in eastern China, especially in the NCP region, including the capital city of Beijing, in which aerosol pollution was significantly enhanced in the already heavily polluted capital city of China.
The structure of a furin-antibody complex explains non-competitive inhibition by steric exclusion of substrate conformers
Authors: Dahms Sven O. , Creemers John W. M. , Schaub Yvonne , Bourenkov Gleb P. , Zögg Thomas , Brandstetter Hans , Than Manuel E. 
Published: September 2016

AbstractProprotein Convertases (PCs) represent highly selective serine proteases that activate their substrates upon proteolytic cleavage. Their inhibition is a promising strategy for the treatment of cancer and infectious diseases. Inhibitory camelid antibodies were developed, targeting the prototypical PC furin. Kinetic analyses of them revealed an enigmatic non-competitive mechanism, affecting the inhibition of large proprotein-like but not small peptidic substrates. Here we present the crystal structures of furin in complex with the antibody Nb14 and of free Nb14 at resolutions of 2.0 Å and 2.3 Å, respectively. Nb14 binds at a site distant to the substrate binding pocket to the P-domain of furin. Interestingly, no major conformational changes were observed upon complex formation, neither for the protease nor for the antibody. Inhibition of furin by Nb14 is instead explained by steric exclusion of specific substrate conformers, explaining why Nb14 inhibits the processing of bulky protein substrates but not of small peptide substrates. This mode of action was further supported by modelling studies with the ternary factor X-furin-antibody complex and a mutation that disrupted the interaction interface between furin and the antibody. The observed binding mode of Nb14 suggests a novel approach for the development of highly specific antibody-based proprotein convertase inhibitors.
CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes
Authors: Yeap Wei Hseun , Wong Kok Loon , Shimasaki Noriko , Teo Esmeralda Chi Yuan , Quek Jeffrey Kim Siang , Yong Hao Xiang , Diong Colin Phipps , Bertoletti Antonio , Linn Yeh Ching , Wong Siew Cheng 
Published: September 2016

AbstractAntibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16− expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies. Engagement of CD16 on monocytes by antibody bound to target cells activated β2-integrins and induced TNFα secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNFα-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFNγ, further enhanced ADCC. Monocytes lacking CD16 did not exert ADCC but acquired this property after CD16 expression was induced by either cytokine stimulation or transient transfection. Notably, CD16+ monocytes from patients with leukemia also exerted potent ADCC. Hence, CD16+ monocytes are important effectors of ADCC, suggesting further developments of this property in the context of cellular therapies for cancer and infectious diseases.
Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A
Authors: Alexander M S , Gasperini M J , Tsai P T , Gibbs D E , Spinazzola J M , Marshall J L , Feyder M J , Pletcher M T , Chekler E L P , Morris C A , Sahin M , Harms J F , Schmidt C J , Kleiman R J , Kunkel L M 
Published: September 2016

AbstractDuchenne muscular dystrophy is caused by mutations in the DYSTROPHIN gene. Although primarily associated with muscle wasting, a significant portion of patients (approximately 25%) are also diagnosed with autism spectrum disorder. We describe social behavioral deficits in dystrophin-deficient mice and present evidence of cerebellar deficits in cGMP production. We demonstrate therapeutic potential for selective inhibitors of the cGMP-specific PDE5A and PDE9A enzymes to restore social behaviors in dystrophin-deficient mice.
Bottom-up proteomics suggests an association between differential expression of mitochondrial proteins and chronic fatigue syndrome
Authors: Ciregia F , Kollipara L , Giusti L , Zahedi R P , Giacomelli C , Mazzoni M R , Giannaccini G , Scarpellini P , Urbani A , Sickmann A , Lucacchini A , Bazzichi L 
Published: September 2016

AbstractChronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by unexplained fatigue not improved by rest. An area of investigation is the likely connection of CFS with defective mitochondrial function. In a previous work, we investigated the proteomic salivary profile in a couple of monozygotic twins discordant for CFS. Following this work, we analyzed mitochondrial proteins in the same couple of twins. Nano-liquid chromatography electrospray ionization mass spectrometry (nano-LC-MS) was used to study the mitochondria extracted from platelets of the twins. Subsequently, we selected three proteins that were validated using western blot analysis in a big cohort of subjects (n=45 CFS; n=45 healthy), using whole saliva (WS). The selected proteins were as follows: aconitate hydratase (ACON), ATP synthase subunit beta (ATPB) and malate dehydrogenase (MDHM). Results for ATPB and ACON confirmed their upregulation in CFS. However, the MDHM alteration was not confirmed. Thereafter, seeing the great variability of clinical features of CFS patients, we decided to analyze the expression of our proteins after splitting patients according to clinical parameters. For each marker, the values were actually higher in the group of patients who had clinical features similar to the ill twin. In conclusion, these results suggest that our potential markers could be one of the criteria to be taken into account for helping in diagnosis. Furthermore, the identification of biomarkers present in particular subgroups of CFS patients may help in shedding light upon the complex entity of CFS. Moreover, it could help in developing tailored treatments.
Papillendiagnostik mithilfe der optischen Kohärenztomografie
Authors: Unterlauft J. , Tegetmeyer H. 
Published: September 2016

Zusammenfassung
Hintergrund: Die Untersuchung des Sehnervenkopfs mit der optischen Kohärenztomografie (OCT) ist beim kooperativen Patienten schnell und einfach durchzuführen und erleichtert die Erkennung und Verlaufskontrolle verschiedener pathologischer Veränderungen der Papille deutlich.
Material und Methoden: Anhand von Beispielen sollen Möglichkeiten und typische Befunde der OCT-Untersuchung der Papille dargestellt werden, um die Erkennung auch seltener Erkrankungen des Sehnervs zu vereinfachen und korrekte Therapieentscheidungen fundiert treffen zu können.
Ergebnisse: Pathologische Veränderungen an der Papille und typische Papillen-OCT-Befunde bei Glaukom, bei verschiedenen Papillenanomalien, bei nicht glaukomatös bedingten Optikusatrophien und bei Papillenschwellungen unterschiedlicher Genese werden beschrieben. Darüber hinaus werden diejenigen OCT-Parameter und Untersuchungsmodalitäten dargestellt, mithilfe derer sich die jeweiligen Krankheitsbilder am einfachsten durch den Untersucher erkennen lassen.
Schlussfolgerung: Die Untersuchung der Papille mittels OCT ermöglicht eine schnelle Diagnostik auch seltener und ophthalmoskopisch schwierig zu erkennender Pathologien des Sehnervenkopfs und genaueste Verlaufsuntersuchungen chronisch-progredienter Erkrankungen. Mithilfe der OCT-Untersuchung der Papille können bei richtiger Anwendung und Auswertung die richtigen Diagnosen korrekt gestellt werden und wichtige Therapieentscheidungen deutlich vereinfacht werden.
Direct observation of grain rotations during coarsening of a semisolid Al–Cu alloy
Authors: Dake Jules M. , Oddershede Jette , Sørensen Henning O. , Werz Thomas , Shatto J. Cole , Uesugi Kentaro , Schmidt Søren , Krill Carl E. 
Published: September 2016

SignificanceComputational modeling of materials phenomena promises to reduce the time and cost of developing new materials and processing techniques—a goal made feasible by rapid advances in computer speed and capacity. Validation of such simulations, however, has been hindered by a lack of 3D experimental data of simultaneously high temporal and spatial resolution. In this study, we exploit 3D X-ray diffraction microscopy to capture the evolution of crystallographic orientations during particle coarsening in a semisolid Al–Cu alloy. The data confirm a long-standing hypothesis that particle rotation is driven (in part) by the dependence of grain boundary energy on misorientation. In addition, the results constitute an experimental foundation for testing the predictive power of next-generation computational models for sintering.
Tyrosine phosphorylation stimulates activity of human RAD51 recombinase through altered nucleoprotein filament dynamics
Authors: Subramanyam Shyamal , Ismail Mohammed , Bhattacharya Ipshita , Spies Maria 
Published: September 2016

Significance
Homologous recombination provides the most accurate means to repair genotoxic DNA lesions. It depends on the assembly of the RAD51 DNA strand exchange protein into a dynamic nucleoprotein filament. The c-Abl tyrosine kinase and its oncogenic counterpart BCR-ABL control RAD51 by phosphorylating tyrosine residues 54 and 315. A nonnatural phosphotyrosine mimetic was used to represent phosphorylated RAD51 and to parse out the importance of Y54 and Y315 phosphorylation. By combining biochemical and single-molecule analyses, we found that Y54 phosphorylation enhances the RAD51 DNA strand exchange activity by altering the nucleoprotein filament properties. In contrast, Y315 phosphorylation has little effect on the RAD51 activities.
DNA-dependent homodimerization, sub-cellular partitioning, and protein destabilization control WUSCHEL levels and spatial patterning
Authors: Rodriguez Kevin , Perales Mariano , Snipes Stephen , Yadav Ram Kishor , Diaz-Mendoza Mercedes , Reddy G. Venugopala 
Published: September 2016

Significance
The growing tips of plants maintain a constant number of stem cells in shoot apical meristems despite a continuous differentiation of stem cell descendants. The levels of homeodomain transcription factor WUSCHEL (WUS) determine the number of stem cells. Although WUSCHEL has been demonstrated to move across cells, the protein signatures that control nuclear levels and spatial patterning have remained elusive. We show that transcriptional regulatory domains also influence nuclear levels of WUS through nuclear-cytoplasmic partitioning and determine the spatial distribution of WUS through DNA binding and homodimerization. Our data also suggest that maintenance of WUSCHEL levels involves protein destabilization. Utilization of the same protein domains to regulate transcription and protein concentration may provide robustness to the spatiotemporal regulation of gene expression.
Shape-programmable magnetic soft matter
Authors: Lum Guo Zhan , Ye Zhou , Dong Xiaoguang , Marvi Hamid , Erin Onder , Hu Wenqi , Sitti Metin 
Published: September 2016

Significance
At small scales, shape-programmable magnetic materials have significant potential to achieve mechanical functionalities that are unattainable by traditional miniature machines. Unfortunately, these materials have only been programmed for a small number of specific applications, as previous work can only rely on human intuition to approximate the required magnetization profile and actuating magnetic fields for such materials. Here, we propose a universal programming methodology that can automatically generate the desired magnetization profile and actuating fields for soft materials to achieve new time-varying shapes. The proposed method can enable other researchers to fully capitalize the potential of shape-programming technologies, allowing them to create a wide range of novel soft active surfaces and devices that are critical in robotics, material science, and medicine.
Humans, water, and the colonization of Australia
Authors: Bird Michael I. , O’Grady Damien , Ulm Sean 
Published: September 2016

Significance
Australia is the driest inhabited continent on earth, but humans dispersed rapidly through much of the arid continental interior after their arrival more than 47,000 y ago. The distribution and connectedness of water across the continent, and particularly in its arid core, played a pivotal role in facilitating and focusing early human dispersal throughout the continent. We analyze the distribution and connectedness of modern permanent water across Australia. The modelled least-cost pathways between permanent water sources indicate that the observed rapid occupation of the continental interior was possible along multiple, well-watered routes and likely was driven by the depletion of high-ranked resources in each newly occupied area over time.
Limited role for methane in the mid-Proterozoic greenhouse
Authors: Olson Stephanie L. , Reinhard Christopher T. , Lyons Timothy W. 
Published: September 2016

SignificanceProterozoic climate dynamics, including both remarkable climate stability during the mid-Proterozoic and extreme low-latitude glaciation in the Neoproterozoic, must be understood in the framework of evolving oxidant reservoirs throughout the Precambrian. We present Earth system model simulations showing that recent constraints on atmospheric oxygen and oceanic sulfate during Proterozoic time have profound implications for marine methane cycling and the accumulation of methane in the atmosphere. Our model results challenge the paradigm of persistently elevated methane during the Precambrian, thus extending the relevance of the faint young Sun paradox throughout the Proterozoic. In light of the possibility of low methane during the mid-Proterozoic, we also suggest a conceptual model for the relationship between oxygenation, methane, and Neoproterozoic Snowball Earth events.
Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression
Authors: Melzi Eleonora , Caporale Marco , Rocchi Mara , Martín Verónica , Gamino Virginia , di Provvido Andrea , Marruchella Giuseppe , Entrican Gary , Sevilla Noemí , Palmarini Massimo 
Published: September 2016

SignificanceArboviruses cause increasingly important human and veterinary diseases. Currently, there is a critical lack of understanding about the nature of arbovirus–host interactions in the lymph nodes (LNs), where the adaptive immune response initiates. We used a hemorrhagic arbovirus of sheep, bluetongue virus (BTV), to unveil the early phases of infection in the natural host. We discovered that BTV modulates the humoral immune response by rapidly infecting and destroying follicular dendritic cells (FDCs) in the host LNs. FDC destruction impairs B-cell activation and antibody production, inducing an immunosuppressive phase associated with virus spread in the animal’s tissues. The novel virus evasion strategy described here provides key insights on the initiation of the immune response and the pathogenesis of arboviral diseases.
Neural correlate of the construction of sentence meaning
Authors: Fedorenko Evelina , Scott Terri L. , Brunner Peter , Coon William G. , Pritchett Brianna , Schalk Gerwin , Kanwisher Nancy 
Published: September 2016

SignificanceHow do circuits of neurons in your brain extract and hold the meaning of a sentence? To start to address this unanswered question, we measured neural activity from the surface of the human brain in patients being mapped out before neurosurgery, as they read sentences. In many electrodes, neural activity increased steadily over the course of the sentence, but the same was not found when participants read lists of words or pronounceable nonwords, or grammatical nonword strings (“Jabberwocky”). This build-up of neural activity appears to reflect neither word meaning nor syntax alone, but the representation of complex meanings.
Pallidal spiking activity reflects learning dynamics and predicts performance
Authors: Schechtman Eitan , Noblejas Maria Imelda , Mizrahi Aviv D. , Dauber Omer , Bergman Hagai 
Published: September 2016

SignificanceThe basal ganglia (BG) are a set of interconnected nuclei deeply buried within the brain that are involved in action selection and habit formation. Classically considered motor nuclei, their role in cognitive performance has become widely appreciated over time. Current models of learning in the BG focus on striatal neurons and the neurotransmitter dopamine, but these do not fully account for observed behaviors. In this paper, we considered the learning-related activity of the external globus pallidus (GPe), a downstream BG nucleus. We show that GPe spiking activity predicts future performance, corresponds with learning dynamics, and decreases as performance becomes more automatic. Taken together, our data reveal the role of GPe in learning and open new avenues for research.