bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism
Authors: Yang Yunlong , Zhang Yin , Iwamoto Hideki , Hosaka Kayoko , Seki Takahiro , Andersson Patrik , Lim Sharon , Fischer Carina , Nakamura Masaki , Abe Mitsuhiko , Cao Renhai , Skov Peter Vilhelm , Chen Fang , Chen Xiaoyun , Lu Yongtian , Nie Guohui , Cao Yihai 
Published: September 2016

AbstractThe impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the ‘off-drug’-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge for uninterrupted and sustained antiangiogenic therapy for treatment of human cancers.
Structural basis underlying viral hijacking of a histone chaperone complex
Authors: Huang Hongda , Deng Zhong , Vladimirova Olga , Wiedmer Andreas , Lu Fang , Lieberman Paul M. , Patel Dinshaw J. 
Published: September 2016

AbstractThe histone H3.3 chaperone DAXX is implicated in formation of heterochromatin and transcription silencing, especially for newly infecting DNA virus genomes entering the nucleus. Epstein-Barr virus (EBV) can efficiently establish stable latent infection as a chromatinized episome in the nucleus of infected cells. The EBV tegument BNRF1 is a DAXX-interacting protein required for the establishment of selective viral gene expression during latency. Here we report the structure of BNRF1 DAXX-interaction domain (DID) in complex with DAXX histone-binding domain (HBD) and histones H3.3-H4. BNRF1 DID contacts DAXX HBD and histones through non-conserved loops. The BNRF1-DAXX interface is responsible for BNRF1 localization to PML-nuclear bodies typically associated with host-antiviral resistance and transcriptional repression. Paradoxically, the interface is also required for selective transcription activation of viral latent cycle genes required for driving B-cell proliferation. These findings reveal molecular details of virus reprogramming of an antiviral histone chaperone to promote viral latency and cellular immortalization.
Peripheral serotonin-mediated system suppresses bone development and regeneration via serotonin 6 G-protein-coupled receptor
Authors: Yun Hyung-Mun , Park Kyung-Ran , Hong Jin Tae , Kim Eun-Cheol 
Published: September 2016

AbstractSerotonin is important in brain functions and involved in neurological diseases. It is also drawn considerable attention in bone disease since it mainly produced by the gut. Serotonin 6 G-protein-coupled receptor (5-HT6R) is clinical targets for the treatment of neurological diseases. However, 5-HT6R as a therapeutic target in bone has not been reported. Herein, we found that 5-HT6R showed higher expression in bone, and its expression was increased during bone remodeling and osteoblast differentiation. The activation of 5-HT6R by ST1936 caused the inhibition of ALP activity and mineralization in primary osteoblast cultures, which was antagonized by SB258585, an antagonist and by the knockdown of 5-HT6R. Further investigation indicated that 5-HT6R inhibited osteoblast differentiation via Jab1 in BMP2 signaling but not PKA and ERK1/2. In vivo studies showed that the activation of 5-HT6R inhibited bone regeneration in the calvarial defect mice and also delayed bone development in newborn mice; this response was antagonized by SB258585. Therefore, our findings indicate a key role of 5-HT6R in bone formation through serotonin originating in the peripheral system, and suggest that it is a novel therapeutic target for drug development in the bone repair and bone diseases.
Tomographic brain imaging with nucleolar detail and automatic cell counting
Authors: Hieber Simone E. , Bikis Christos , Khimchenko Anna , Schweighauser Gabriel , Hench Jürgen , Chicherova Natalia , Schulz Georg , Müller Bert 
Published: September 2016

AbstractBrain tissue evaluation is essential for gaining in-depth insight into its diseases and disorders. Imaging the human brain in three dimensions has always been a challenge on the cell level. In vivo methods lack spatial resolution, and optical microscopy has a limited penetration depth. Herein, we show that hard X-ray phase tomography can visualise a volume of up to 43 mm3 of human post mortem or biopsy brain samples, by demonstrating the method on the cerebellum. We automatically identified 5,000 Purkinje cells with an error of less than 5% at their layer and determined the local surface density to 165 cells per mm2 on average. Moreover, we highlight that three-dimensional data allows for the segmentation of sub-cellular structures, including dendritic tree and Purkinje cell nucleoli, without dedicated staining. The method suggests that automatic cell feature quantification of human tissues is feasible in phase tomograms obtained with isotropic resolution in a label-free manner.
Pesticide exposure and risk of Alzheimer’s disease: a systematic review and meta-analysis
Authors: Yan Dandan , Zhang Yunjian , Liu Liegang , Yan Hong 
Published: September 2016

AbstractEvidence suggests that lifelong cumulative exposure to pesticides may generate lasting toxic effects on the central nervous system and contribute to the development of Alzheimer’s disease (AD). A number of reports indicate a potential association between long-term/low-dose pesticide exposure and AD, but the results are inconsistent. Therefore, we conducted a meta-analysis to clarify this association. Relevant studies were identified according to inclusion criteria. Summary odds ratios (ORs) were calculated using fixed-effects models. A total of seven studies were included in our meta-analysis. A positive association was observed between pesticide exposure and AD (OR = 1.34; 95% confidence interval [CI] = 1.08, 1.67; n = 7). The summary ORs with 95% CIs from the crude and adjusted effect size studies were 1.14 (95% CI = 0.94, 1.38; n = 7) and 1.37 (95% CI = 1.09, 1.71; n = 5), respectively. The sensitivity analyses of the present meta-analysis did not substantially modify the association between pesticide exposure and AD. Subgroup analyses revealed that high-quality studies tended to show significant relationships. The present meta-analysis suggested a positive association between pesticide exposure and AD, confirming the hypothesis that pesticide exposure is a risk factor for AD. Further high-quality cohort and case-control studies are required to validate a causal relationship.
Different coding strategies for the perception of stable and changeable facial attributes
Authors: Taubert Jessica , Alais David , Burr David 
Published: September 2016

AbstractPerceptual systems face competing requirements: improving signal-to-noise ratios of noisy images, by integration; and maximising sensitivity to change, by differentiation. Both processes occur in human vision, under different circumstances: they have been termedpriming,orserial dependencies,leading to positive sequential effects; andadaptationorhabituation, which leads to negative sequential effects. We reasoned that for stable attributes, such as the identity and gender of faces, the system should integrate: while for changeable attributes like facial expression, it should also engage contrast mechanisms to maximise sensitivity to change. Subjects viewed a sequence of images varying simultaneously in gender and expression and scored each as male or female,andhappy or sad. We found strong and consistent positive serial dependencies for gender and negative dependency for expression, showing that both processes can operate at the same time, on the same stimuli, depending on the attribute being judged. The results point to highly sophisticated mechanisms for optimizing use of past information, either by integration or differentiation, depending on the permanence of that attribute.
Population and life-stage specific sensitivities to temperature and salinity stress in barnacles
Authors: Nasrolahi Ali , Havenhand Jonathan , Wrange Anna-Lisa , Pansch Christian 
Published: September 2016

AbstractTemperature and salinity shape the distribution and genetic structure of marine communities. Future warming and freshening will exert an additional stress to coastal marine systems. The extent to which organisms respond to these shifts will, however, be mediated by the tolerances of all life-stages and populations of species and their potential to adapt. We investigated nauplius and cypris larvae of the barnacle Balanus (Amphibalanus) improvisus from the Swedish west coast with respect to temperature (12, 20, and 28 °C) and salinity (5, 15, and 30) tolerances. Warming accelerated larval development and increased overall survival and subsequent settlement success. Nauplii developed and metamorphosed best at intermediate salinity. This was also observed in cypris larvae when the preceding nauplii stages had been reared at a salinity of 30. Direct comparisons of the present findings with those on a population from the more brackish Baltic Sea demonstrate contrasting patterns. We conclude that i) B. improvisus larvae within the Baltic region will be favoured by near-future seawater warming and freshening, that ii) salinity tolerances of larvae from the two different populations reflect salinities in their native habitats, but are nonetheless suboptimal and that iii) this species is generally highly plastic with regard to salinity.
Structural and electronic transformation pathways in morphotropic BiFeO3
Authors: Sharma P. , Heo Y. , Jang B.-K. , Liu Y. Y. , Li J. Y. , Yang C.-H. , Seidel J. 
Published: September 2016

AbstractPhase boundaries in multiferroics, in which (anti-)ferromagnetic, ferroelectric and ferroelastic order parameters coexist, enable manipulation of magnetism and electronic properties by external electric fields through switching of the polarization in the material. It has been shown that the strain-driven morphotropic phase boundaries in a single-phase multiferroic such as BiFeO3 (BFO) can exhibit distinct electronic conductivity. However, the control of ferroelectric and phase switching and its correlation with phase boundary conductivity in this material has been a significant challenge. Supported by a thermodynamic approach, here we report a concept to precisely control different switching pathways and the associated control of electronic conductivity in mixed phase BFO. This work demonstrates a critical step to control and use non-volatile strain-conductivity coupling at the nanoscale. Beyond this observation, it provides a framework for exploring a route to control multiple order parameters coupled to ferroelastic and ferroelectric order in multiferroic materials.
High saturation magnetization of γ-Fe2O3 nano-particles by a facile one-step synthesis approach
Authors: Cao Derang , Li Hao , Pan Lining , Li Jianan , Wang Xicheng , Jing Panpan , Cheng Xiaohong , Wang Wenjie , Wang Jianbo , Liu Qingfang 
Published: September 2016

AbstractWe have demonstrated the synthesis of γ-Fe2O3 nano-particles through a facile and novel calcination process in the air. There is no pH regulation, gas atmosphere, additive, centrifugation or other complicated procedures during the preparing process. A detailed formation process of the nano-particles is proposed and DMF as a polar solvent may slower the reaction process of calcination. The structures, morphologies and magnetic properties of γ-Fe2O3 nano-particles were investigated systematically and the pure γ-Fe2O3 nano-particles obtained at 200 °C display uniform morphology good magnetic property. The saturation magnetization of obtained pure γ-Fe2O3 is about 74 emu/g, which is comparable with bulk material (76 emu/g) and larger than other results. In addition, the photocatalytic activity for degradation of methylene blue is also studied, which shows proper photocatalytic activity.
The BR domain of PsrP interacts with extracellular DNA to promote bacterial aggregation; structural insights into pneumococcal biofilm formation
Authors: Schulte Tim , Mikaelsson Cecilia , Beaussart Audrey , Kikhney Alexey , Deshmukh Maya , Wolniak Sebastian , Pathak Anuj , Ebel Christine , Löfling Jonas , Fogolari Federico , Henriques-Normark Birgitta , Dufrêne Yves F. , Svergun Dmitri , Nygren Per-Åke , Achour Adnane 
Published: September 2016

AbstractThe major human pathogen Streptococcus pneumoniae is a leading cause of disease and death worldwide. Pneumococcal biofilm formation within the nasopharynx leads to long-term colonization and persistence within the host. We have previously demonstrated that the capsular surface-associated pneumococcal serine rich repeat protein (PsrP), key factor for biofilm formation, binds to keratin-10 (KRT10) through its microbial surface component recognizing adhesive matrix molecule (MSCRAMM)-related globular binding region domain (BR187–385). Here, we show that BR187–385 also binds to DNA, as demonstrated by electrophoretic mobility shift assays and size exclusion chromatography. Further, heterologous expression of BR187–378 or the longer BR120–378 construct on the surface of a Gram-positive model host bacterium resulted in the formation of cellular aggregates that was significantly enhanced in the presence of DNA. Crystal structure analyses revealed the formation of BR187–385 homo-dimers via an intermolecular β-sheet, resulting in a positively charged concave surface, shaped to accommodate the acidic helical DNA structure. Furthermore, small angle X-ray scattering and circular dichroism studies indicate that the aggregate-enhancing N-terminal region of BR120–166 adopts an extended, non-globular structure. Altogether, our results suggest that PsrP adheres to extracellular DNA in the biofilm matrix and thus promotes pneumococcal biofilm formation.
Synthesis of jet fuel range branched cycloalkanes with mesityl oxide and 2-methylfuran from lignocellulose
Authors: Li Shanshan , Li Ning , Wang Wentao , Li Lin , Wang Aiqin , Wang Xiaodong , Zhang Tao 
Published: September 2016

AbstractJet fuel range branched cycloalkanes with high density (0.82 g mL−1) and low freezing point (217–219 K) was first prepared by the solvent-free intramolecular aldol condensation of the trione from the hydrolysis of the alkylation product of mesityl oxide and 2-methylfuran (or the one-pot reaction of mesityl oxide, 2-methylfuran and water), followed by hydrodeoxygenation (HDO).
Pore structure modified diatomite-supported PEG composites for thermal energy storage
Authors: Qian Tingting , Li Jinhong , Deng Yong 
Published: September 2016

AbstractA series of novel composite phase change materials (PCMs) were tailored by blending PEG and five kinds of diatomite via a vacuum impregnation method. To enlarge its pore size and specific surface area, different modification approaches including calcination, acid treatment, alkali leaching and nano-silica decoration on the microstructure of diatomite were outlined. Among them, 8 min of 5 wt% NaOH dissolution at 70 °C has been proven to be the most effective and facile. While PEG melted during phase transformation, the maximum load of PEG could reach 70 wt.%, which was 46% higher than that of the raw diatomite. The apparent activation energy of PEG in the composite was 1031.85 kJ·mol−1, which was twice higher than that of the pristine PEG. Moreover, using the nano-silica decorated diatomite as carrier, the maximum PEG load was 66 wt%. The composite PCM was stable in terms of thermal and chemical manners even after 200 cycles of melting and freezing. All results indicated that the obtained composite PCMs were promising candidate materials for building applications due to its large latent heat, suitable phase change temperature, excellent chemical compatibility, improved supercooling extent, high thermal stability and long-term reliability.
Stability of rhombohedral phases in vanadium at high-pressure and high-temperature: first-principles investigations
Authors: Wang Yi X. , Wu Q. , Chen Xiang R. , Geng Hua Y. 
Published: September 2016

AbstractThe pressure-induced transition of vanadium from BCC to rhombohedral structures is unique and intriguing among transition metals. In this work, the stability of these phases is revisited by using density functional theory. At finite temperatures, a novel transition of rhombohedral phases back to BCC phase induced by thermal electrons is discovered. This reentrant transition is found not driven by phonons, instead it is the electronic entropy that stabilizes the latter phase, which is totally out of expectation. Parallel to this transition, we find a peculiar and strong increase of the shear modulus C44 with increasing temperature. It is counter-intuitive in the sense that it suggests an unusual harding mechanism of vanadium by temperature. With these stability analyses, the high-pressure and finite-temperature phase diagram of vanadium is proposed. Furthermore, the dependence of the stability of RH phases on the Fermi energy and chemical environment is investigated. The results demonstrate that the position of the Fermi level has a significant impact on the phase stability and follows the band-filling argument. Besides the Fermi surface nesting, we find that the localization/delocalization of the d orbitals also contributes to the instability of rhombohedral distortions in vanadium.
Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy
Authors: Guo Rui , Lin Bin , Pan Jing Fei , Liong Emily C. , Xu Ai Min , Youdim Moussa , Fung Man Lung , So Kwok Fai , Tipoe George L. 
Published: September 2016

AbstractAcute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury.
Synthesis of Mg-Fe-Cl hydrotalcite-like nanoplatelets as an oral phosphate binder: evaluations of phosphorus intercalation activity and cellular cytotoxicity
Authors: Lung Yung-Feng , Sun Ying-Sui , Lin Chun-Kai , Uan Jun-Yen , Huang Her-Hsiung 
Published: September 2016

AbstractThe patients with end-stage of renal disease (ESRD) need to take oral phosphate binder. Traditional phosphate binders may leave the disadvantage of aluminum intoxication or cardiac calcification. Herein, Mg-Fe-Clhydrotalcite-like nanoplatelet (HTln) is for the first time characterized as potential oral phosphate binder, with respect to its phosphorus uptake capacity in cow milk and cellular cytotoxicity. A novel method was developed for synthesizing the Mg-Fe-ClHTln powder in different Mg2+: Fe3+ratios where the optimization was 2.8:1. Addition of 0.5 g Mg-Fe-ClHTln in cow milk could reduce its phosphorus content by 40% in 30 min and by 65% in 90 min. In low pH environment, the Mg-Fe-ClHTln could exhibit relatively high performance for uptaking phosphorus. During a 90 min reaction of the HTln in milk, no phosphorus restoration occurred.In-vitrocytotoxicity assay of Mg-Fe-ClHTln revealed no potential cellular cytotoxicity. The cells that were cultured in the HTln extract-containing media were even more viable than cells that were cultured in extract-free media (blank control). The Mg-Fe-ClHTln extract led to hundred ppm of Mg ion and some ppm of Fe ion in the media, should be a positive effect on the good cell viability.
In silico identification of enhancers on the basis of a combination of transcription factor binding motif occurrences
Authors: Fang Yaping , Wang Yunlong , Zhu Qin , Wang Jia , Li Guoliang 
Published: September 2016

AbstractEnhancers interact with gene promoters and form chromatin looping structures that serve important functions in various biological processes, such as the regulation of gene transcription and cell differentiation. However, enhancers are difficult to identify because they generally do not have fixed positions or consensus sequence features, and biological experiments for enhancer identification are costly in terms of labor and expense. In this work, several models were built by using various sequence-based feature sets and their combinations for enhancer prediction. The selected features derived from a recursive feature elimination method showed that the model using a combination of 141 transcription factor binding motif occurrences from 1,422 transcription factor position weight matrices achieved a favorably high prediction accuracy superior to that of other reported methods. The models demonstrated good prediction accuracy for different enhancer datasets obtained from different cell lines/tissues. In addition, prediction accuracy was further improved by integration of chromatin state features. Our method is complementary to wet-lab experimental methods and provides an additional method to identify enhancers.
Novel Stable Compounds in the C-H-O Ternary System at High Pressure
Authors: Saleh Gabriele , Oganov Artem R. 
Published: September 2016

AbstractThe chemistry of the elements is heavily altered by high pressure, with stabilization of many new and often unexpected compounds, the emergence of which can profoundly change models of planetary interiors, where high pressure reigns. The C-H-O system is one of the most important planet-forming systems, but its high-pressure chemistry is not well known. Here, using state-of-the-art variable-composition evolutionary searches combined with quantum-mechanical calculations, we explore the C-H-O system at pressures up to 400 GPa. Besides uncovering new stable polymorphs of high-pressure elements and known molecules, we predicted the formation of new compounds. A 2CH4:3H2inclusion compound forms at low pressure and remains stable up to 215 GPa. Carbonic acid (H2CO3), highly unstable at ambient conditions, was predicted to form exothermically at mild pressure (about 1 GPa). As pressure rises, it polymerizes and, above 314 GPa, reacts with water to form orthocarbonic acid (H4CO4). This unexpected high-pressure chemistry is rationalized by analyzing charge density and electron localization function distributions and implications for general chemistry and planetary science are also discussed.