bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer
Authors: Yang Moran , Zhang Guodong , Wang Yiying , He Mengdi , Xu Qing , Lu Jiaqi , Liu Haiou , Xu Congjian 
Published: August 2020

Abstract
Background
Tumour associated neutrophils (TANs) play a controversial role in regulating immune surveillance and immune evasion in various malignancies. Here, we investigated the relevance of TANs with the prognosis and immune microenvironment of epithelial ovarian cancer (EOC).

Methods
We characterised TANs using flow cytometric analysis and immunofluorescence analysis. The prognostic merit of TANs in EOC was evaluated using cox regression analysis. Furthermore, we explored the therapeutic merit of targeting Notch signalling in EOC and determined its involvement in the immune microenvironment.

Results
High level of TANs is associated with a dismal prognosis and immune tolerance in EOC. TANs impaired cytotoxic effects of CD8+ T cells partly through Jagged2 (JAG2). Notch pathway blocked using γ-secretase inhibitor LY3039478 and anti-JAG2 antibody led to retarded tumour growth and augmented cytotoxic effects of CD8+ T cells. IL-8 contributes to the recruitment of TANs and the induction of JAG2 expression in TANs. Blockade of CXCR2 signalling reduces tumour growth rate, accompanied by a decreasing amount of TANs and increasing activity of CD8+ T cells. JAG2+TANs is an independent predictor of clinical outcomes.

Conclusion
JAG2+TANs are closely linked to IL-8-driven immune evasion microenvironment and may serve as a promising therapeutic target for the reinvigoration of anti-tumour immunity.
Endogenous activity modulates stimulus and circuit-specific neural tuning and predicts perceptual behavior
Authors: Li Yuanning , Ward Michael J. , Richardson R. Mark , G’Sell Max , Ghuman Avniel Singh 
Published: August 2020

AbstractPerception reflects not only sensory inputs, but also the endogenous state when these inputs enter the brain. Prior studies show that endogenous neural states influence stimulus processing through non-specific, global mechanisms, such as spontaneous fluctuations of arousal. It is unclear if endogenous activity influences circuit and stimulus-specific processing and behavior as well. Here we use intracranial recordings from 30 pre-surgical epilepsy patients to show that patterns of endogenous activity are related to the strength of trial-by-trial neural tuning in different visual category-selective neural circuits. The same aspects of the endogenous activity that relate to tuning in a particular neural circuit also correlate to behavioral reaction times only for stimuli from the category that circuit is selective for. These results suggest that endogenous activity can modulate neural tuning and influence behavior in a circuit- and stimulus-specific manner, reflecting a potential mechanism by which endogenous neural states facilitate and bias perception.
Mechanisms of drug interactions between translation-inhibiting antibiotics
Authors: Kavčič Bor , Tkačik Gašper , Bollenbach Tobias 
Published: August 2020

AbstractAntibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by “translation bottlenecks”: points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of “continuous epistasis” in bacterial physiology.
In vitro Cas9-assisted editing of modular polyketide synthase genes to produce desired natural product derivatives
Authors: Kudo Kei , Hashimoto Takuya , Hashimoto Junko , Kozone Ikuko , Kagaya Noritaka , Ueoka Reiko , Nishimura Takehiro , Komatsu Mamoru , Suenaga Hikaru , Ikeda Haruo , Shin-ya Kazuo 
Published: August 2020

AbstractOne major bottleneck in natural product drug development is derivatization, which is pivotal for fine tuning lead compounds. A promising solution is modifying the biosynthetic machineries of middle molecules such as macrolides. Although intense studies have established various methodologies for protein engineering of type I modular polyketide synthase(s) (PKSs), the accurate targeting of desired regions in the PKS gene is still challenging due to the high sequence similarity between its modules. Here, we report an innovative technique that adapts in vitro Cas9 reaction and Gibson assembly to edit a target region of the type I modular PKS gene. Proof-of-concept experiments using rapamycin PKS as a template show that heterologous expression of edited biosynthetic gene clusters produced almost all the desired derivatives. Our results are consistent with the promiscuity of modular PKS and thus, our technique will provide a platform to generate rationally designed natural product derivatives for future drug development.
Pupil-linked arousal signals track the temporal organization of events in memory
Authors: Clewett David , Gasser Camille , Davachi Lila 
Published: August 2020

AbstractEveryday life unfolds continuously, yet we tend to remember past experiences as discrete event sequences or episodes. Although this phenomenon has been well documented, the neuromechanisms that support the transformation of continuous experience into distinct and memorable episodes remain unknown. Here, we show that changes in context, or event boundaries, elicit a burst of autonomic arousal, as indexed by pupil dilation. Event boundaries also lead to the segmentation of adjacent episodes in later memory, evidenced by changes in memory for the temporal duration, order, and perceptual details of recent event sequences. These subjective and objective changes in temporal memory are also related to distinct temporal features of pupil dilations to boundaries as well as to the temporal stability of more prolonged pupil-linked arousal states. Collectively, our findings suggest that pupil measures reflect both stability and change in ongoing mental context representations, which in turn shape the temporal structure of memory.
Adsorption and activation of molecular oxygen over atomic copper(I/II) site on ceria
Authors: Kang Liqun , Wang Bolun , Bing Qiming , Zalibera Michal , Büchel Robert , Xu Ruoyu , Wang Qiming , Liu Yiyun , Gianolio Diego , Tang Chiu C. , Gibson Emma K. , Danaie Mohsen , Allen Christopher , Wu Ke , Marlow Sushila , Sun Ling-dong , He Qian , Guan Shaoliang , Savitsky Anton , Velasco-Vélez Juan J. , Callison June , Kay Christopher W. M. , Pratsinis Sotiris E. , Lubitz Wolfgang , Liu Jing-yao , Wang Feng Ryan 
Published: August 2020

AbstractSupported atomic metal sites have discrete molecular orbitals. Precise control over the energies of these sites is key to achieving novel reaction pathways with superior selectivity. Here, we achieve selective oxygen (O2) activation by utilising a framework of cerium (Ce) cations to reduce the energy of 3d orbitals of isolated copper (Cu) sites. Operando X-ray absorption spectroscopy, electron paramagnetic resonance and density-functional theory simulations are used to demonstrate that a [Cu(I)O2]3− site selectively adsorbs molecular O2, forming a rarely reported electrophilic η2-O2 species at 298 K. Assisted by neighbouring Ce(III) cations, η2-O2 is finally reduced to two O2−, that create two Cu–O–Ce oxo-bridges at 453 K. The isolated Cu(I)/(II) sites are ten times more active in CO oxidation than CuO clusters, showing a turnover frequency of 0.028 ± 0.003 s−1 at 373 K and 0.01 bar PCO. The unique electronic structure of [Cu(I)O2]3− site suggests its potential in selective oxidation.
Space-charge-limited electron and hole currents in hybrid organic-inorganic perovskites
Authors: Sajedi Alvar Mohammad , Blom Paul W. M. , Wetzelaer Gert-Jan A. H. 
Published: August 2020

AbstractHybrid organic-inorganic perovskites are promising materials for the application in solar cells and light-emitting diodes. However, the basic current-voltage behavior for electrons and holes is still poorly understood in these semiconductors due to their mixed electronic-ionic character. Here, we present the analysis of space-charge-limited electron and hole currents in the archetypical perovskite methyl ammonium lead iodide (MAPbI3). We demonstrate that the frequency dependence of the permittivity plays a crucial role in the analysis of space-charge-limited currents and their dependence on voltage scan rate and temperature. Using a mixed electronic-ionic device model based on experimentally determined parameters, the current-voltage characteristics of single-carrier devices are accurately reproduced. Our results reveal that in our solution processed MAPbI3 thin films transport of electrons dominates over holes. Furthermore, we show that the direction of the hysteresis in the current-voltage characteristics provides a fingerprint for the sign of the dominant moving ionic species.
Within-individual phenotypic plasticity in flowers fosters pollination niche shift
Authors: Gómez José M. , Perfectti Francisco , Armas Cristina , Narbona Eduardo , González-Megías Adela , Navarro Luis , DeSoto Lucía , Torices Rubén 
Published: August 2020

AbstractPhenotypic plasticity, the ability of a genotype of producing different phenotypes when exposed to different environments, may impact ecological interactions. We study here how within-individual plasticity inMoricandia arvensisflowers modifies its pollination niche. During spring, this plant produces large, cross-shaped, UV-reflecting lilac flowers attracting mostly long-tongued large bees. However, unlike most co-occurring species,M. arvensiskeeps flowering during the hot, dry summer due to its plasticity in key vegetative traits. Changes in temperature and photoperiod in summer trigger changes in gene expression and the production of small, rounded, UV-absorbing white flowers that attract a different assemblage of generalist pollinators. This shift in pollination niche potentially allows successful reproduction in harsh conditions, facilitatingM. arvensisto face anthropogenic perturbations and climate change.
Human practices promote presence and abundance of disease-transmitting mosquito species
Authors: Schrama Maarten , Hunting Ellard R. , Beechler Brianna R. , Guarido Milehna M. , Govender Danny , Nijland Wiebe , van ‘t Zelfde Maarten , Venter Marietjie , van Bodegom Peter M. , Gorsich Erin E. 
Published: August 2020

AbstractHumans alter the environment at unprecedented rates through habitat destruction, nutrient pollution and the application of agrochemicals. This has recently been proposed to act as a potentially significant driver of pathogen-carrying mosquito species (disease vectors) that pose a health risk to humans and livestock. Here, we use a unique set of locations along a large geographical gradient to show that landscapes disturbed by a variety of anthropogenic stressors are consistently associated with vector-dominated mosquito communities for a wide range of human and livestock infections. This strongly suggests that human alterations to the environment promote the presence and abundance of disease vectors across large spatial extents. As such, it warrants further studies aimed at unravelling mechanisms underlying vector prevalence in mosquito communities, and opens up new opportunities for preventative action and predictive modelling of vector borne disease risks in relation to degradation of natural ecosystems.
Clinical evaluation of fully automated molecular diagnostic system “Simprova” for influenza virus, respiratory syncytial virus, and human metapneumovirus
Authors: Takayama Ikuyo , Semba Shohei , Yokono Kota , Saito Shinji , Nakauchi Mina , Kubo Hideyuki , Kaida Atsushi , Shiomi Masashi , Terada Akihiro , Murakami Kiyotaka , Kaji Katsushi , Kiya Keiichi , Sawada Yoshitaka , Oba Kunihiro , Asai Sadasaburo , Yonekawa Toshihiro , Watanabe Hidetoshi , Segawa Yuji , Notomi Tsugunori , Kageyama Tsutomu 
Published: August 2020

AbstractInfluenza virus, respiratory syncytial virus, and human metapneumovirus commonly cause acute upper and lower respiratory tract infections, especially in children and the elderly. Although rapid antigen detection tests for detecting these infections have been introduced recently, these are less sensitive than nucleic acid amplification tests. More recently, highly sensitive point-of-care testings (POCTs) have been developed based on nucleic acid amplification tests, which are easy to use in clinical settings. In this study, loop-mediated isothermal amplification (LAMP)-based POCT “Simprova” to detect influenza A and B viruses, respiratory syncytial virus, and human metapneumovirus was developed. Simprova system is fully automated and does not require skilled personnel. In addition, positive results can be achieved faster than with PCR. In this study, the accuracy of the POCT was retrospectively analyzed using 241 frozen stocked specimens. Additionally, the usability of the Simprova at clinical sites was assessed in a prospective clinical study using 380 clinical specimens and compared to those of real-time PCR and rapid antigen detection test. The novel LAMP-based POCT demonstrated high sensitivity and specificity in characterizing clinical specimens from patients with influenza-like illnesses. The Simprova is a powerful tool for early diagnosis of respiratory viral infections in point-of-care settings.
Simultaneous detection of ethambutol and pyrazinamide with IL@CoFe2O4NPs@MWCNTs fabricated glassy carbon electrode
Authors: Chokkareddy Rajasekhar , Kanchi Suvardhan , Inamuddin  
Published: August 2020

AbstractFor the first time, we report a novel electrochemical sensor for the simultaneous detection of ethambutol (ETB) and pyrazinamide (PZM) using 1-ethyl-3-methylimidazolium tetrafluoroborate ([Emim][BF4]) ionic liquid (IL) assimilated with multiwalled carbon nanotubes (MWCNTs) decorated cobalt ferrite nanoparticles (CoFe2O4NPs) on the surface of glassy carbon electrode (GCE). The surface morphological and electrochemical properties of the IL@CoFe2O4NPs@MWCNTs was characterized with X-ray diffraction (XRD), transmission electron microscope (TEM), thermogravimetric analysis (TGA), fourier transform infrared spectroscopy (FTIR) and cyclic voltammetry (CV), differential pulse voltammetry (DPV) respectively. Moreover, the obtained results of CV demonstrated that the 9-folds enhancement in the electrochemical signals was achieved with IL@CoFe2O4NPs@MWCNTs@GCE compared to that of a bare GCE. Additionally, the simultaneous electrochemical detection of ETB and PZM was successfully accomplished using IL@CoFe2O4NPs@MWCNTs over a wide-range of concentration with good limit of detection (3S/m) of 0.0201 and 0.010 μM respectively. The findings of this study identify IL@CoFe2O4NPs@MWCNTs@GCE has promising abilities of simultaneous detection of ETB and PZM in pharmaceutical formulations.
Additive interactions of nanoparticulate ZnO with copper, manganese and iron in Pisum sativum L., a hydroponic study
Authors: Skiba Elżbieta , Michlewska Sylwia , Pietrzak Monika , Wolf Wojciech M. 
Published: August 2020

AbstractWidespread occurrence of ZnO nanoparticles in environment follows the growing number of applications either in technology or agriculture. The impact of five forms of nanoparticulate ZnO on copper, manganese and iron uptake by Pisum sativum L. cultivated in Hoagland solutions was investigated. Plants were collected after twelve days of zinc administration. Effect of bulk ZnO has also been studied. Initial zinc concentration was 100 mg L−1. Nanoparticles were characterized by the Transmission Electron Microscopy, Dynamic Light Scattering and Zeta potential measurements. Metal contents were analyzed using the Atomic Absorption Spectrometry with flame atomization for samples digested in a microwave closed system. Analysis of variance indicated that zinc species at either molecular or nanoscale levels altered Cu, Mn and Fe uptake and their further transport in pea plants. In particular, significant reduction of Mn and Fe combined with the Cu increase was observed. Additive interactions originated by nanoparticles affect the heavy metals uptake and indicate pollutants migration pathways in plants. Unfortunately, regulations for the plant cultivation were formulated when anthropogenic nanoparticles were not in common use. They underestimate complexity of metals interactions in either plant or habitat. Our results indicate that these additive interactions cannot be neglected and deserve further investigations.
Unraveling the complex enzymatic machinery making a key galactolipid in chloroplast membrane: a multiscale computer simulation
Authors: Makshakova Olga , Breton Christelle , Perez Serge 
Published: August 2020

AbstractChloroplast membranes have a high content of the uncharged galactolipids monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG). These galactolipids are essential for the biogenesis of plastids and functioning of the photosynthetic machinery. A monotopic glycosyltransferase, monogalactosyldiacylglycerol synthase synthesizes the bulk of MGDG. It is embedded in the outer leaflet of the inner envelope membrane of chloroplasts. The protein transfers a galactose residue from UDP-galactose to diacylglycerol (DAG); it needs anionic lipids such as phosphatidylglycerol (PG) to be active. The intricacy of the organization and the process of active complex assembly and synthesis have been investigated at the Coarse-Grained and All-Atom of computer simulation levels to cover large spatial and temporal scales. The following self-assembly process and catalytic events can be drawn; (1) in the membrane, in the absence of protein, there is a spontaneous formation of PG clusters to which DAG molecules associate, (2) a reorganization of the clusters occurs in the vicinity of the protein once inserted in the membrane, (3) an accompanying motion of the catalytic domain of the protein brings DAG in the proper position for the formation of the active complex MGD1/UDP-Gal/DAG/PG for which an atomistic model of interaction is proposed.
Overexpression of miR-669m inhibits erythroblast differentiation
Authors: Kotaki Ryutaro , Kawashima Masaharu , Yamaguchi Asuka , Suzuki Naoto , Koyama-Nasu Ryo , Ogiya Daisuke , Okuyama Kazuki , Yamamoto Yuichiro , Takamatsu Masako , Kurosaki Natsumi , Ando Kiyoshi , Murata Akihiko , Ohtsuka Masato , Nakagawa So , Katagiri Koko , Kotani Ai 
Published: August 2020

AbstractMicroRNAs (miRNAs), one of small non-coding RNAs, regulate many cell functions through their post-transcriptionally downregulation of target genes. Accumulated studies have revealed that miRNAs are involved in hematopoiesis. In the present study, we investigated effects of miR-669m overexpression on hematopoiesis in mouse in vivo, and found that erythroid differentiation was inhibited by the overexpression. Our bioinformatic analyses showed that candidate targets of miR-669m which are involved in the erythropoiesis inhibition are A-kinase anchoring protein 7 (Akap7) and X-linked Kx blood group (Xk) genes. These two genes were predicted as targets of miR-669m by two different in silico methods and were upregulated in late erythroblasts in a public RNA-seq data, which was confirmed with qPCR. Further, miR-669m suppressed luciferase reporters for 3′ untranslated regions of Akap7 and Xk genes, which supports these genes are direct targets of miR-669m. Physiologically, miR-669m was not expressed in the erythroblast. In conclusion, using miR-669m, we found Akap7 and Xk, which may be involved in erythroid differentiation, implying that manipulating these genes could be a therapeutic way for diseases associated with erythropoiesis dysfunction.
Quantum thermodynamics of single particle systems
Authors: Ali Md. Manirul , Huang Wei-Ming , Zhang Wei-Min 
Published: August 2020

AbstractThermodynamics is built with the concept of equilibrium states. However, it is less clear how equilibrium thermodynamics emerges through the dynamics that follows the principle of quantum mechanics. In this paper, we develop a theory of quantum thermodynamics that is applicable for arbitrary small systems, even for single particle systems coupled with a reservoir. We generalize the concept of temperature beyond equilibrium that depends on the detailed dynamics of quantum states. We apply the theory to a cavity system and a two-level system interacting with a reservoir, respectively. The results unravels (1) the emergence of thermodynamics naturally from the exact quantum dynamics in the weak system-reservoir coupling regime without introducing the hypothesis of equilibrium between the system and the reservoir from the beginning; (2) the emergence of thermodynamics in the intermediate system-reservoir coupling regime where the Born-Markovian approximation is broken down; (3) the breakdown of thermodynamics due to the long-time non-Markovian memory effect arisen from the occurrence of localized bound states; (4) the existence of dynamical quantum phase transition characterized by inflationary dynamics associated with negative dynamical temperature. The corresponding dynamical criticality provides a border separating classical and quantum worlds. The inflationary dynamics may also relate to the origin of big bang and universe inflation. And the third law of thermodynamics, allocated in the deep quantum realm, is naturally proved.
Chemical profile and phytotoxic action of Onopordum acanthium essential oil
Authors: Wei Caixia , Zhou Shixing , Shi Kai , Zhang Chi , Shao Hua 
Published: August 2020

AbstractThe potential of utilizing Onopordum acanthium essential oil and its major constituents as environment friendly herbicides was investigated. In total 29, 25, and 18 compounds were identified from flower, leaf, and stem oils, representing 94.77%, 80.02%, and 90.74% of the total oil, respectively. Flower and stem oils were found to be rich in n-alkanes, which accounted for 57.33% in flower oil, and 82.33% in stem oil. Flower oil exerted potent inhibitory activity on both receiver species, Amaranthus retroflexus and Poa annua, which nearly completely suppressed seed germination at 5 mg/mL, and β-eudesmol is the most likely responsible compound for its phytotoxicity; in comparison, leaf and stem oils exhibited much weaker inhibitory activity on A. retroflexus, and stimulatory effect on P. annua when tested concentration was below 2.5 mg/mL. Alkanes in the oils were found to exert relatively weak plant growth regulatory activity. This report is the first on the chemical profile and phytotoxic action of O. acanthium oil as well as the phytotoxicity of β-eudesmol.