bluuebunny/crossref_metadata_2025_split huggingface dataset:
An intrinsic tumour eviction mechanism in Drosophila mediated by steroid hormone signalling
Authors: Jiang Yanrui , Seimiya Makiko , Schlumpf Tommy Beat , Paro Renato 
Published: August 2018

AbstractPolycomb group proteins are epigenetic regulators maintaining transcriptional memory during cellular proliferation. In Drosophila larvae, malfunction of Polyhomeotic (Ph), a member of the PRC1 silencing complex, results in neoplastic growth. Here, we report an intrinsic tumour suppression mechanism mediated by the steroid hormone ecdysone during metamorphosis. Ecdysone alters neoplastic growth into a nontumorigenic state of the mutant ph cells which then become eliminated during adult stage. We demonstrate that ecdysone exerts this function by inducing a heterochronic network encompassing the activation of the microRNA lethal-7, which suppresses its target gene chronologically inappropriate morphogenesis. This pathway can also promote remission of brain tumours formed in brain tumour mutants, revealing a restraining of neoplastic growth in different tumour types. Given the conserved role of let-7, the identification and molecular characterization of this innate tumour eviction mechanism in flies might provide important clues towards the exploitation of related pathways for human tumour therapy.
SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis
Authors: Zhou Huanjiao Jenny , Xu Zhe , Wang Zongren , Zhang Haifeng , Zhuang Zhen W. , Simons Michael , Min Wang 
Published: August 2018

AbstractRegulation of VEGFR2 represents an important mechanism for the control of angiogenesis. VEGFR2 activity can be regulated by post-translational modifications such as ubiquitination and acetylation. However, whether VEGFR2 can be regulated by SUMOylation has not been investigated. Here we show that endothelial-specific deletion of the SUMO endopeptidase SENP1 reduces pathological angiogenesis and tissue repair during hindlimb ischemia, and VEGF-induced angiogenesis in the cornea, retina, and ear. SENP1-deficient endothelial cells show increased SUMOylation of VEGFR2 and impaired VEGFR2 signalling. SUMOylation at lysine 1270 retains VEGFR2 in the Golgi and reduces its surface expression, attenuating VEGFR2-dependent signalling. Moreover, we find that SENP1 is downregulated and VEGFR2 hyper-SUMOylated in diabetic settings and that expression of a non-SUMOylated form of VEGFR2 rescues angiogenic defects in diabetic mice. These results show that VEGFR2 is regulated by deSUMOylation during pathological angiogenesis, and propose SENP1 as a potential therapeutic target for the treatment of diabetes-associated angiogenesis.
Divergent global-scale temperature effects from identical aerosols emitted in different regions
Authors: Persad Geeta G. , Caldeira Ken 
Published: August 2018

AbstractThe distribution of anthropogenic aerosols’ climate effects depends on the geographic distribution of the aerosols themselves. Yet many scientific and policy discussions ignore the role of emission location when evaluating aerosols’ climate impacts. Here, we present new climate model results demonstrating divergent climate responses to a fixed amount and composition of aerosol—emulating China’s present-day emissions—emitted from 8 key geopolitical regions. The aerosols’ global-mean cooling effect is fourteen times greater when emitted from the highest impact emitting region (Western Europe) than from the lowest (India). Further, radiative forcing, a widely used climate response proxy, fails as an effective predictor of global-mean cooling for national-scale aerosol emissions in our simulations; global-mean forcing-to-cooling efficacy differs fivefold depending on emitting region. This suggests that climate accounting should differentiate between aerosols emitted from different countries and that aerosol emissions’ evolving geographic distribution will impact the global-scale magnitude and spatial distribution of climate change.
Mathematical modelling of the impact of expanding levels of malaria control interventions on Plasmodium vivax
Authors: White Michael T. , Walker Patrick , Karl Stephan , Hetzel Manuel W. , Freeman Tim , Waltmann Andreea , Laman Moses , Robinson Leanne J. , Ghani Azra , Mueller Ivo 
Published: August 2018

AbstractPlasmodium vivax poses unique challenges for malaria control and elimination, notably the potential for relapses to maintain transmission in the face of drug-based treatment and vector control strategies. We developed an individual-based mathematical model of P. vivax transmission calibrated to epidemiological data from Papua New Guinea (PNG). In many settings in PNG, increasing bed net coverage is predicted to reduce transmission to less than 0.1% prevalence by light microscopy, however there is substantial risk of rebounds in transmission if interventions are removed prematurely. In several high transmission settings, model simulations predict that combinations of existing interventions are not sufficient to interrupt P. vivax transmission. This analysis highlights the potential options for the future of P. vivax control: maintaining existing public health gains by keeping transmission suppressed through indefinite distribution of interventions; or continued development of strategies based on existing and new interventions to push for further reduction and towards elimination.
mTOR-dependent phosphorylation controls TFEB nuclear export
Authors: Napolitano Gennaro , Esposito Alessandra , Choi Heejun , Matarese Maria , Benedetti Valerio , Di Malta Chiara , Monfregola Jlenia , Medina Diego Luis , Lippincott-Schwartz Jennifer , Ballabio Andrea 
Published: August 2018

AbstractDuring starvation the transcriptional activation of catabolic processes is induced by the nuclear translocation and consequent activation of transcription factor EB (TFEB), a master modulator of autophagy and lysosomal biogenesis. However, how TFEB is inactivated upon nutrient refeeding is currently unknown. Here we show that TFEB subcellular localization is dynamically controlled by its continuous shuttling between the cytosol and the nucleus, with the nuclear export representing a limiting step. TFEB nuclear export is mediated by CRM1 and is modulated by nutrient availability via mTOR-dependent hierarchical multisite phosphorylation of serines S142 and S138, which are localized in proximity of a nuclear export signal (NES). Our data on TFEB nucleo-cytoplasmic shuttling suggest an unpredicted role of mTOR in nuclear export.
Accelerated vortex dynamics across the magnetic 3D-to-2D crossover in disordered superconductors
Authors: Eley Serena , Willa Roland , Miura Masashi , Sato Michio , Leroux Maxime , Henry Michael David , Civale Leonardo 
Published: August 2018

AbstractDisorder can have remarkably disparate consequences in superconductors, driving superconductor–insulator transitions in ultrathin films by localizing electron pairs and boosting the supercurrent carrying capacity of thick films by localizing vortices (magnetic flux lines). Though the electronic 3D-to-2D crossover at material thicknesses d ~ ξ (coherence length) is well studied, a similarly consequential magnetic crossover at d ~ Lc (pinning length) that should drastically alter material properties remains largely underexamined. According to collective pinning theory, vortex segments of length Lc bend to adjust to energy wells provided by point defects. Consequently, if d truncates Lc, a change from elastic to rigid vortex dynamics should increase the rate of thermally activated vortex motion S. Here, we characterize the dependence of S on sample thickness in Nb and cuprate films. The results for Nb are consistent with collective pinning theory, whereas creep in the cuprate is strongly influenced by sparse large precipitates. We leverage the sensitivity of S to d to determine the generally unknown scale Lc, establishing a new route for extracting pinning lengths in heterogeneously disordered materials.
Transcriptional insights into the pyramided resistance to rice bacterial blight
Authors: Gao Lifen , Fang Zhiwei , Zhou Junfei , Li Lun , Lu Long , Li Lili , Li Tiantian , Chen Lihong , Zhang Weixiong , Zhai Wenxue , Peng Hai 
Published: August 2018

AbstractThe pyramiding of resistance (R) genes provides broad-spectrum and durable resistance to plant diseases. However, the genetic basis for bacterial blight (BB) resistance remains unclear. The BB R gene pyramided line IRBB54, which expressesxa5andXa21, possessed a higher level of resistance than both singleRgene lines. Large-scale genotyping of genetic markers in this study revealed similar genetic backgrounds among the near-isogenic lines (NILs), suggesting that resistance in the resistant NILs was mainly conferred by the individual R genes or the interaction between them. Transcriptome analysis demonstrated that more than 50% of the differentially expressed genes (DEGs), and more than 70% of the differentially expressed functions, were shared between IRBB54 and IRBB5 or IRBB21. Most of the DEGs in the resistant NILs were downregulated and are predicted to function in cellular and biological process. The DEGs common among the resistant NILs mainly showed non-additive expression patterns and enrichment in stress-related pathways. The differential expression of agronomic trait-controlled genes in the resistant NILs, especially in IRBB54, indicated the existence of potential side-effects resulting from gene pyramiding. Our findings contribute to the understanding of R gene pyramiding, as well as its effects on targeted and non-targeted trait(s).
Controlling Dzyaloshinskii-Moriya Interaction via Chirality Dependent Atomic-Layer Stacking, Insulator Capping and Electric Field
Authors: Yang Hongxin , Boulle Olivier , Cros Vincent , Fert Albert , Chshiev Mairbek 
Published: August 2018

AbstractUsing first-principles calculations, we demonstrate several approaches to control Dzyaloshinskii-Moriya Interaction (DMI) in ultrathin films with perpendicular magnetic anisotropy. First, we find that DMI is significantly enhanced when the ferromagnetic (FM) layer is sandwiched between nonmagnetic (NM) layers inducing additive DMI in NM1/FM/NM2 structures. For instance, when two NM layers are chosen to induce DMI of opposite chirality in Co, e.g. NM1 representing Au, Ir, Al or Pb, and NM2 being Pt, the resulting DMI in NM1/Co/Pt trilayers is enhanced compared to Co/Pt bilayers. Moreover, DMI can be significantly enhanced further in case of using FM layer comprising Fe and Co layers. Namely, it is found that the DMI in Ir/Fe/Co/Pt structure can be enhanced by 80% compared to that of Co/Pt bilayers reaching a very large DMI amplitude of 5.59 meV/atom. Our second approach for enhancing DMI is to use oxide capping layer. We show that DMI is enhanced by 60% in Oxide/Co/Pt structures compared to Co/Pt bilayers. Moreover, we unveiled the DMI mechanism at Oxide/Co interface due to Rashba effect, which is different to Fert-Levy DMI at FM/NM interfaces. Finally, we demonstrate that DMI amplitude can be modulated using an electric field with an efficiency factor comparable to that of the electric field control of perpendicular magnetic anisotropy in transition metal/oxide interfaces. These approaches of DMI controlling pave the way for skyrmion and domain wall motion-based spintronic applications.
Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence
Authors: Rocha Marina Campos , de Godoy Krissia Franco , Bannitz-Fernandes Renata , Fabri João H. T. Marilhano , Barbosa Mayra M. Ferrari , de Castro Patrícia Alves , Almeida Fausto , Goldman Gustavo Henrique , da Cunha Anderson Ferreira , Netto Luis E. S. , de Oliveira Marcos Antonio , Malavazi Iran 
Published: August 2018

AbstractStanding among the front defense strategies against pathogens, host phagocytic cells release various oxidants. Therefore, pathogens have to cope with stressful conditions at the site of infection. Peroxiredoxins (Prx) are highly reactive and abundant peroxidases that can support virulence and persistence of pathogens in distinct hosts. Here, we revealed that the opportunistic human pathogen A. fumigatus presents three 1-Cys Prx (Prx6 subfamily), which is unprecedented. We showed that PrxB and PrxC were in mitochondria, while Prx1 was in cytosol. As observed for other Prxs, recombinant Prx1 and PrxC decomposed H2O2 at elevated velocities (rate constants in the 107 M−1s−1 range). Deletion mutants for each Prx displayed higher sensitivity to oxidative challenge in comparison with the wild-type strain. Additionally, cytosolic Prx1 was important for A. fumigatus survival upon electron transport dysfunction. Expression of Prxs was dependent on the SakAHOG1 MAP kinase and the Yap1YAP1 transcription factor, a global regulator of the oxidative stress response in fungi. Finally, cytosolic Prx1 played a major role in pathogenicity, since it is required for full virulence, using a neutropenic mouse infection model. Our data indicate that the three 1-Cys Prxs act together to maintain the redox balance of A. fumigatus.
Complete chloroplast genome sequence of Fagopyrum dibotrys: genome features, comparative analysis and phylogenetic relationships
Authors: Wang Xumei , Zhou Tao , Bai Guoqing , Zhao Yuemei 
Published: August 2018

AbstractFagopyrum dibotrys, belongs to Polygonaceae family, is one of national key conserved wild plants of China with important medicinal and economic values. Here, the complete chloroplast (cp) genome sequence of F. dibotrys is reported. The cp genome size is 159,919 bp with a typical quadripartite structure and consisting of a pair of inverted repeat regions (30,738 bp) separated by large single copy region (85,134 bp) and small single copy region (13,309 bp). Sequencing analyses indicated that the cp genome encodes 131 genes, including 80 protein-coding genes, 28 tRNA genes and 4 rRNA genes. The genome structure, gene order and codon usage are typical of angiosperm cp genomes. We also identified 48 simple sequence repeats (SSR) loci, fewer of them are distributed in the protein-coding sequences compared to the noncoding regions. Comparison of F. dibotrys cp genome to other Polygonaceae cp genomes indicated the inverted repeats (IRs) and coding regions were more conserved than single copy and noncoding regions, and several variation hotspots were detected. Coding gene sequence divergence analyses indicated that five genes (ndhK, petL rpoC2, ycf1, ycf2) were subject to positive selection. Phylogenetic analysis among 42 species based on cp genomes and 50 protein-coding genes indicated a close relationship between F. dibotrys and F. tataricum. In summary, the complete cp genome sequence of F. dibotrys reported in this study will provide useful plastid genomic resources for population genetics and pave the way for resolving phylogenetic relationships of order Caryophyllales.
Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells
Authors: Brownlee William J. , Seib F. Philipp 
Published: August 2018

AbstractBreast cancer cells adapt to the hypoxic tumoral environment by undergoing changes in metabolism, cell signalling, endo-lysosomal receptor uptake and recycling. The resulting hypoxic cell phenotype has the potential to undermine the therapeutic efficacy of nanomedicines designed for endocytic uptake and specific intracellular trafficking. The aim of this study was to examine the impact of hypoxia and simulated reperfusion on the in vitro uptake and release of nanomedicines by human breast cancer cells. Cells were exposed to a hypoxic preconditioning treatment in 1% oxygen for 6 and 24 hours to induce temporal changes in the hypoxic circuit (e.g. HIF-1α expression). The preconditioned cells were then dosed with nanoparticles for 45 or 180 minutes emulating nanomedicine access following tumor reperfusion. Hypoxic preconditioning significantly increased nanoparticle retention by up to 10% when compared to normoxic cultures, with the greatest relative difference between normoxic and hypoxic cultures occurring with a 45 minute dosing interval. Exocytosis studies indicated that the preconditioned cells had a significantly increased nanoparticle efflux (up to 9%) when compared to normoxic cells. Overall, we were able to show that hypoxic preconditioning regulates both the endocytosis and exocytosis of nanomedicines in human breast cancer cells.
High expression of EZH2 as a marker for the differential diagnosis of malignant and benign myogenic tumors
Authors: Zhang Ning , Zeng Zhi , Li Shaobo , Wang Fei , Huang Peng 
Published: August 2018

AbstractOverlap in morphologic features between malignant and benign myogenic tumors, such as leiomyosarcoma (LMS) vs. leiomyoma as well as rhabdomyosarcoma (RMS) vs. rhabdomyoma, often makes differential diagnosis difficult and challenging. Here the expressions of Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste 12 (SUZ12), retinoblastoma protein associated protein 46 (RbAp46), Embryonic Ectoderm Development (EED) and ki-67 protein were detected by immunohistochemistry to evaluate their values in differential diagnosis. The expression of EZH2 mRNA was investigated by analyzing the Gene Expression Omnibus Datasets. The results demonstrated that EZH2 protein was detected in 81.25% (26/32) of LMS and 70.58% (36/51) of RMS, whereas none of leiomyoma (n = 16), rhabdomyoma (n = 15) and normal tissues (n = 31) showed positive immunostaining (p < 0.05). EZH2 protein was found to have a sensitivity of 91.30% and specificity of 100% in distinguishing well-differentiated LMS from cellular leiomyoma, and a sensitivity of 92.86% and specificity of 100% in distinguishing well-differentiated embryonal rhabdomyosarcoma (ERMS) from fetal rhabdomyoma. Besides, the expression of EZH2 mRNA was higher in LMS and RMS than in benign tumors (p < 0.05). The expressions of SUZ12 and RbAp46 protein were higher in RMS than in rhabdomyoma (p < 0.05). Conclusively, the high expression of EZH2 is a promising marker in distinguishing well–differentiated LMS from cellular leiomyoma, or well–differentiated ERMS from fetal rhabdomyoma, and the upregulation of EZH2 protein expression may occur at transcriptional level.
Including planocerid flatworms in the diet effectively toxifies the pufferfish, Takifugu niphobles
Authors: Itoi Shiro , Ueda Hiroyuki , Yamada Riko , Takei Mitsuki , Sato Tatsunori , Oshikiri Shotaro , Wajima Yoshiki , Ogata Ryuya , Oyama Hikaru , Shitto Takahiro , Okuhara Kazuya , Tsunashima Tadasuke , Sawayama Eitaro , Sugita Haruo 
Published: August 2018

AbstractBeginning with the larval stages, marine pufferfish such as Takifugu niphobles contain tetrodotoxin (TTX), an extremely potent neurotoxin. Although highly concentrated TTX has been detected in adults and juveniles of these fish, the source of the toxin has remained unclear. Here we show that TTX in the flatworm Planocera multitentaculata contributes to the toxification of the pufferfish throughout the life cycle of the flatworm. A species-specific PCR method was developed for the flatworm, and the specific DNA fragment was detected in the digesta of wild pufferfish adults. Predation experiments showed that flatworm larvae were eaten by the pufferfish juveniles, and that the two-day postprandial TTX content in these pufferfish was 20–50 μg/g. Predation experiments additionally showed flatworm adults were also eaten by pufferfish young, and after two days of feeding, TTX accumulated in the skin, liver and intestine of the pufferfish.
Towards the geometric structure of small supported Au9 clusters on Si
Authors: Chekrygina D. , Rothkirch A. , Baev I. , Kielgast F. , Pandit P. , Wurth W. , Martins M. 
Published: August 2018

AbstractUltra-small clusters containing few atoms are of high interest in both fundamental research and applications due to their specific functional, magnetic or chemical properties which depend on size and composition. The experimental results of the morphology of the size-selected clusters, consisting of few atoms can be an ideal benchmark for sophisticated theoretical models. With this motivation we have investigated the geometrical structure of mass-selected Au9 clusters deposited on a silicon substrate prepared by soft-landing conditions. We present results obtained experimentally by Grazing-Incidence Small-Angle X-ray Scattering (GISAXS). Considering the ultra-small size of the clusters and small quantities of material on the surface, we combined advanced techniques which allowed us to investigate the surface structure of the sample. The resulting structural sizes are in concordance with cluster theory. Using a model-based approach, the advanced X-ray techniques allow for understanding how to resolve the possible cluster structure, identify optimal experimental conditions and obtain the probable morphological information which is challenging to be obtained otherwise.
Thymosin Alpha1-Fc Modulates the Immune System and Down-regulates the Progression of Melanoma and Breast Cancer with a Prolonged Half-life
Authors: Wang Fanwen , Yu Tingting , Zheng Heng , Lao Xingzhen 
Published: August 2018

AbstractThymosin alpha 1 (Tα1) is a biological response modifier that has been introduced into markets for treating several diseases. Given the short serum half-life of Tα1 and the rapid development of Fc fusion proteins, we used genetic engineering method to construct the recombinant plasmid to express Tα1-Fc (Fc domain of human IgG4) fusion protein. A single-factor experiment was performed with different inducers of varying concentrations for different times to get the optimal condition of induced expression. Pure proteins higher than 90.3% were obtained by using 5 mM lactose for 4 h with a final production about 160.4 mg/L. Thein vivoserum half-life of Tα1-Fc is 25 h, almost 13 times longer than Tα1 in mice models. Also, the long-acting protein has a stronger activity in repairing immune injury through increasing number of lymphocytes. Tα1-Fc displayed a more effective antitumor activity in the 4T1 and B16F10 tumor xenograft models by upregulating CD86 expression, secreting IFN-γ and IL-2, and increasing the number of tumor-infiltrating CD4+ T and CD8+ T cells. Our study on the novel modified Tα1 with the Fc segment provides valuable information for the development of new immunotherapy in cancer.