bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critical role of caveolin-1 in aflatoxin B1-induced hepatotoxicity via the regulation of oxidation and autophagy
Authors: Xu Qingqiang , Shi Wenwen , Lv Pan , Meng Wenqi , Mao Guanchao , Gong Chuchu , Chen Yongchun , Wei Youheng , He Xiaowen , Zhao Jie , Han Hua , Sun Mingxue , Xiao Kai 
Published: January 2020

AbstractAflatoxin B1 (AFB1) is a potent hepatocarcinogen in humans and exposure to AFB1 is known to cause both acute and chronic hepatocellular injury. As the liver is known to be the main target organ of aflatoxin, it is important to identify the key molecules that participate in AFB1-induced hepatotoxicity and to investigate their underlying mechanisms. In this study, the critical role of caveolin-1 in AFB1-induced hepatic cell apoptosis was examined. We found a decrease in cell viability and an increase in oxidation and apoptosis in human hepatocyte L02 cells after AFB1 exposure. In addition, the intracellular expression of caveolin-1 was increased in response to AFB1 treatment. Downregulation of caveolin-1 significantly alleviated AFB1-induced apoptosis and decreased cell viability, whereas overexpression of caveolin-1 reversed these effects. Further functional analysis showed that caveolin-1 participates in AFB1-induced oxidative stress through its interaction with Nrf2, leading to the downregulation of cellular antioxidant enzymes and the promotion of oxidative stress-induced apoptosis. In addition, caveolin-1 was found to regulate AFB1-induced autophagy. This finding was supported by the effect that caveolin-1 deficiency promoted autophagy after AFB1 treatment, leading to the inhibition of apoptosis, whereas overexpression of caveolin-1 inhibited autophagy and accelerated apoptosis. Interestingly, further investigation showed that caveolin-1 participates in AFB1-induced autophagy by regulating the EGFR/PI3K-AKT/mTOR signaling pathway. Taken together, our data reveal that caveolin-1 plays a crucial role in AFB1-induced hepatic cell apoptosis via the regulation of oxidation and autophagy, which provides a potential target for the development of novel treatments to combat AFB1 hepatotoxicity.
Arc silence aggravates traumatic neuronal injury via mGluR1-mediated ER stress and necroptosis
Authors: Chen Tao , Zhu Jie , Wang Yu-Hai , Hang Chun-Hua 
Published: January 2020

AbstractDelayed neuronal death is associated with neurological deficits and mortality after traumatic brain injury (TBI), where post-synaptic density (PSD) proteins are thought to play key roles. The immediate-early gene (IEG) coded protein Arc is a brain-specific PSD protein that controls synaptic plasticity and learning behaviors. In this study, we investigated the expression and biological function of Arc in neuronal death after TBI in an in vitro model mimicked by traumatic neuronal injury (TNI) in cortical neurons. TNI caused a temporal increase of Arc expression at 3 and 6 h. Knockdown of Arc expression using small interfering RNA (Si-Arc-3) promoted TNI-induced cytotoxicity and apoptosis. The results of western blot showed that Si-Arc-3 transfection further enhanced the activation of endoplasmic reticulum (ER) stress-associated factors, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and caspase-12 after TNI. In addition, knockdown of Arc significantly increased expression of (receptor-interacting protein kinase 1) RIP1 and the number of necroptotic cells, which were apparently prevented by necrostatin-1 (Nec-1). The results of immunostaining and western blot showed that knockdown of Arc activated the metabotropic glutamate receptor 1 (mGluR1) and intracellular Ca2+ release in neurons. Mechanistically, the Si-Arc-3-induced activation of ER stress-associated factors, RIP1 expression, apoptosis, and necroptosis were partially reversed by the mGluR1 antagonist AIDA. In summary, our data suggest that silence of Arc expression aggravates neuronal death after TNI by promoting apoptosis and necroptosis. These data support for the first time that Arc may represent a novel candidate for therapies against TBI.
GSK3β is a key regulator of the ROS-dependent necrotic death induced by the quinone DMNQ
Authors: Ciotti Sonia , Iuliano Luca , Cefalù Sebastiano , Comelli Marina , Mavelli Irene , Di Giorgio Eros , Brancolini Claudio 
Published: January 2020

AbstractSignaling pathways controlling necrosis are still mysterious and debated. We applied a shRNA-based viability screen to identify critical elements of the necrotic response. We took advantage from a small molecule (G5) that makes covalent adducts with free thiols by Michael addition and elicits multiple stresses. In cells resistant to apoptosis, G5 triggers necrosis through the induction of protein unfolding, glutathione depletion, ER stress, proteasomal impairments, and cytoskeletal stress. The kinase GSK3β was isolated among the top hits of the screening. Using the quinone DMNQ, a ROS generator, we demonstrate that GSK3β is involved in the regulation of ROS-dependent necrosis. Our results have been validated using siRNA and by knocking-out GSK3β with the CRISPR/Cas9 technology. In response to DMNQ GSK3β is activated by serine 9 dephosphorylation, concomitantly to Akt inactivation. During the quinone-induced pro-necrotic stress, GSK3β gradually accumulates into the nucleus, before the collapse of the mitochondrial membrane potential. Accumulation of ROS in response to DMNQ is impaired by the absence of GSK3β. We provide evidence that the activities of the obligatory two-electrons reducing flavoenzymes, NQO1 (NAD(P)H quinone dehydrogenase 1) and NQO2 are required to suppress DMNQ-induced necrosis. In the absence of GSK3β the expression of NQO1 and NQO2 is dramatically increased, possibly because of an increased transcriptional activity of NRF2. In summary, GSK3β by blunting the anti-oxidant response and particularly NQO1 and NQO2 expression, favors the appearance of necrosis in response to ROS, as generated by the quinone DMNQ.
Structures of lipoprotein signal peptidase II from Staphylococcus aureus complexed with antibiotics globomycin and myxovirescin
Authors: Olatunji Samir , Yu Xiaoxiao , Bailey Jonathan , Huang Chia-Ying , Zapotoczna Marta , Bowen Katherine , Remškar Maja , Müller Rolf , Scanlan Eoin M. , Geoghegan Joan A. , Olieric Vincent , Caffrey Martin 
Published: January 2020

AbstractAntimicrobial resistance is a major global threat that calls for new antibiotics. Globomycin and myxovirescin are two natural antibiotics that target the lipoprotein-processing enzyme, LspA, thereby compromising the integrity of the bacterial cell envelope. As part of a project aimed at understanding their mechanism of action and for drug development, we provide high-resolution crystal structures of the enzyme from the human pathogen methicillin-resistantStaphylococcus aureus(MRSA) complexed with globomycin and with myxovirescin. Our results reveal an instance of convergent evolution. The two antibiotics possess different molecular structures. Yet, they appear to inhibit identically as non-cleavable tetrahedral intermediate analogs. Remarkably, the two antibiotics superpose along nineteen contiguous atoms that interact similarly with LspA. This 19-atom motif recapitulates a part of the substrate lipoprotein in its proposed binding mode. Incorporating this motif into a scaffold with suitable pharmacokinetic properties should enable the development of effective antibiotics with built-in resistance hardiness.
Ocean Carbon Storage across the middle Miocene: a new interpretation for the Monterey Event
Authors: Sosdian S. M. , Babila T. L. , Greenop R. , Foster G. L. , Lear C. H. 
Published: January 2020

AbstractThe Miocene Climatic Optimum (MCO, 14–17 Ma) was ~3–4 °C warmer than present, similar to estimates for 2100. Coincident with the MCO is the Monterey positive carbon isotope (δ13C) excursion, with oceans more depleted in 12C relative to 13C than any time in the past 50 Myrs. The long-standing Monterey Hypothesis uses this excursion to invoke massive marine organic carbon burial and draw-down of atmospheric CO2 as a cause for the subsequent Miocene Climate Transition and Antarctic glaciation. However, this hypothesis cannot explain the multi-Myr lag between the δ13C excursion and global cooling. We use planktic foraminiferal B/Ca, δ11B, δ13C, and Mg/Ca to reconstruct surface ocean carbonate chemistry and temperature. We propose that the MCO was associated with elevated oceanic dissolved inorganic carbon caused by volcanic degassing, global warming, and sea-level rise. A key negative feedback of this warm climate was the organic carbon burial on drowned continental shelves.
Epidermal control of axonal attachment via β-spectrin and the GTPase-activating protein TBC-10 prevents axonal degeneration
Authors: Coakley Sean , Ritchie Fiona K. , Galbraith Kate M. , Hilliard Massimo A. 
Published: January 2020

AbstractNeurons are subjected to strain due to body movement and their location within organs and tissues. However, how they withstand these forces over the lifetime of an organism is still poorly understood. Here, focusing on touch receptor neuron-epidermis interactions usingCaenorhabditis elegansas a model system, we show that UNC-70/β-spectrin and TBC-10, a conserved GTPase-activating protein, function non-cell-autonomously within the epidermis to dynamically maintain attachment of the axon. We reveal that, in response to strain, UNC-70/β-spectrin and TBC-10 stabilize trans-epidermal hemidesmosome attachment structures which otherwise become lost, causing axonal breakage and degeneration. Furthermore, we show that TBC-10 regulates axonal attachment and maintenance by inactivating RAB-35, and reveal functional conservation of these molecules with their vertebrate orthologs. Finally, we demonstrate that β-spectrin functions in this context non-cell-autonomously. We propose a model in which mechanically resistant epidermal attachment structures are maintained by UNC-70/β-spectrin and TBC-10 during movement, preventing axonal detachment and degeneration.
Image quality guided smart rotation improves coverage in microscopy
Authors: He Jiaye , Huisken Jan 
Published: January 2020

AbstractFluorescence microscopy is an essential tool for biological discoveries. There is a constant demand for better spatial resolution across a larger field of view. Although strides have been made to improve the theoretical resolution and speed of the optical instruments, in mesoscopic samples, image quality is still largely limited by the optical properties of the sample. In Selective Plane Illumination Microscopy (SPIM), the achievable optical performance is hampered by optical degradations encountered in both the illumination and detection. Multi-view imaging, either through sample rotation or additional optical paths, is a popular strategy to improve sample coverage. In this work, we introduce a smart rotation workflow that utilizes on-the-fly image analysis to identify the optimal light sheet imaging orientations. The smart rotation workflow outperforms the conventional approach without additional hardware and achieves a better sample coverage using the same number of angles or less and thereby reduces data volume and phototoxicity.
Sensing of HIV-1 by TLR8 activates human T cells and reverses latency
Authors: Meås Hany Zekaria , Haug Markus , Beckwith Marianne Sandvold , Louet Claire , Ryan Liv , Hu Zhenyi , Landskron Johannes , Nordbø Svein Arne , Taskén Kjetil , Yin Hang , Damås Jan Kristian , Flo Trude Helen 
Published: January 2020

AbstractDuring HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well understood. Here we show that synthetic ligands of TLR8 boosted T cell receptor signaling, resulting in increased cytokine production and upregulation of surface activation markers. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation towards Th1 and Th17. In addition, we found that endosomal HIV induced cytokine secretion from CD4+ T cells in a TLR8-specific manner. TLR8 engagement also enhanced HIV-1 replication and potentiated the reversal of latency in patient-derived T cells. The adjuvant TLR8 activity in T cells can contribute to viral dissemination in the lymph node and low-grade inflammation in HIV patients. In addition, it can potentially be exploited for therapeutic targeting and vaccine development.
Sub-1.4eV bandgap inorganic perovskite solar cells with long-term stability
Authors: Hu Mingyu , Chen Min , Guo Peijun , Zhou Hua , Deng Junjing , Yao Yudong , Jiang Yi , Gong Jue , Dai Zhenghong , Zhou Yunxuan , Qian Feng , Chong Xiaoyu , Feng Jing , Schaller Richard D. , Zhu Kai , Padture Nitin P. , Zhou Yuanyuan 
Published: January 2020

AbstractState-of-the-art halide perovskite solar cells have bandgaps larger than 1.45 eV, which restricts their potential for realizing the Shockley-Queisser limit. Previous search for low-bandgap (1.2 to 1.4 eV) halide perovskites has resulted in several candidates, but all are hybrid organic-inorganic compositions, raising potential concern regarding device stability. Here we show the promise of an inorganic low-bandgap (1.38 eV) CsPb0.6Sn0.4I3 perovskite stabilized via interface functionalization. Device efficiency up to 13.37% is demonstrated. The device shows high operational stability under one-sun-intensity illumination, with T80 and T70 lifetimes of 653 h and 1045 h, respectively (T80 and T70 represent efficiency decays to 80% and 70% of the initial value, respectively), and long-term shelf stability under nitrogen atmosphere. Controlled exposure of the device to ambient atmosphere during a long-term (1000 h) test does not degrade the efficiency. These findings point to a promising direction for achieving low-bandgap perovskite solar cells with high stability.
Electron Bernstein waves driven by electron crescents near the electron diffusion region
Authors: Li W. Y. , Graham D. B. , Khotyaintsev Yu. V. , Vaivads A. , André M. , Min K. , Liu K. , Tang B. B. , Wang C. , Fujimoto K. , Norgren C. , Toledo-Redondo S. , Lindqvist P.-A. , Ergun R. E. , Torbert R. B. , Rager A. C. , Dorelli J. C. , Gershman D. J. , Giles B. L. , Lavraud B. , Plaschke F. , Magnes W. , Le Contel O. , Russell C. T. , Burch J. L. 
Published: January 2020

AbstractThe Magnetospheric Multiscale (MMS) spacecraft encounter an electron diffusion region (EDR) of asymmetric magnetic reconnection at Earth’s magnetopause. The EDR is characterized by agyrotropic electron velocity distributions on both sides of the neutral line. Various types of plasma waves are produced by the magnetic reconnection in and near the EDR. Here we report large-amplitude electron Bernstein waves (EBWs) at the electron-scale boundary of the Hall current reversal. The finite gyroradius effect of the outflow electrons generates the crescent-shaped agyrotropic electron distributions, which drive the EBWs. The EBWs propagate toward the central EDR. The amplitude of the EBWs is sufficiently large to thermalize and diffuse electrons around the EDR. The EBWs contribute to the cross-field diffusion of the electron-scale boundary of the Hall current reversal near the EDR.
Boosting fast energy storage by synergistic engineering of carbon and deficiency
Authors: Deng Shengjue , Zhu He , Wang Guizhen , Luo Mi , Shen Shenghui , Ai Changzhi , Yang Liang , Lin Shiwei , Zhang Qinghua , Gu Lin , Liu Bo , Zhang Yan , Liu Qi , Pan Guoxiang , Xiong Qinqin , Wang Xiuli , Xia Xinhui , Tu Jiangping 
Published: January 2020

AbstractExploring advanced battery materials with fast charging/discharging capability is of great significance to the development of modern electric transportation. Herein we report a powerful synergistic engineering of carbon and deficiency to construct high-quality three/two-dimensional cross-linked Ti2Nb10O29−x@C composites at primary grain level with conformal and thickness-adjustable boundary carbon. Such exquisite boundary architecture is demonstrated to be capable of regulating the mechanical stress and concentration of oxygen deficiency for desired performance. Consequently, significantly improved electronic conductivity and enlarged lithium ion diffusion path, shortened activation process and better structural stability are realized in the designed Ti2Nb10O29−x@C composites. The optimized Ti2Nb10O29−x@C composite electrode shows fast charging/discharging capability with a high capacity of 197 mA h g−1 at 20 C (∼3 min) and excellent long-term durability with 98.7% electron and Li capacity retention over 500 cycles. Most importantly, the greatest applicability of our approach has been demonstrated by various other metal oxides, with tunable morphology, structure and composition.
Conversion of a conventional superconductor into a topological superconductor by topological proximity effect
Authors: Trang C. X. , Shimamura N. , Nakayama K. , Souma S. , Sugawara K. , Watanabe I. , Yamauchi K. , Oguchi T. , Segawa K. , Takahashi T. , Ando Yoichi , Sato T. 
Published: January 2020

AbstractRealization of topological superconductors (TSCs) hosting Majorana fermions is a central challenge in condensed-matter physics. One approach is to use the superconducting proximity effect (SPE) in heterostructures, where a topological insulator contacted with a superconductor hosts an effective p-wave pairing by the penetration of Cooper pairs across the interface. However, this approach suffers a difficulty in accessing the topological interface buried deep beneath the surface. Here, we propose an alternative approach to realize topological superconductivity without SPE. In a Pb(111) thin film grown on TlBiSe2, we discover that the Dirac-cone state of substrate TlBiSe2 migrates to the top surface of Pb film and obtains an energy gap below the superconducting transition temperature of Pb. This suggests that a Bardeen-Cooper-Schrieffer superconductor is converted into a TSC by the topological proximity effect. Our discovery opens a route to manipulate topological superconducting properties of materials.
Color-tunable single-fluorophore supramolecular system with assembly-encoded emission
Authors: Wang Qian , Zhang Qi , Zhang Qi-Wei , Li Xin , Zhao Cai-Xin , Xu Tian-Yi , Qu Da-Hui , Tian He 
Published: January 2020

AbstractRegulating the fluorescent properties of organic small molecules in a controlled and dynamic manner has been a fundamental research goal. Although several strategies have been exploited, realizing multi-color molecular emission from a single fluorophore remains challenging. Herein, we demonstrate an emissive system by combining pyrene fluorophore and acylhydrazone units, which can generate multi-color switchable fluorescent emissions at different assembled states. Two kinds of supramolecular tools, amphiphilic self-assembly and γ-cyclodextrin mediated host-guest recognition, are used to manipulate the intermolecular aromatic stacking distances, resulting in the tunable fluorescent emission ranging from blue to yellow, including a pure white-light emission. Moreover, an external chemical signal, amylase, is introduced to control the assembly states of the system on a time scale, generating a distinct dynamic emission system. The dynamic properties of this multi-color fluorescent system can be also enabled in a hydrogel network, exhibiting a promising potential for intelligent fluorescent materials.
Realistic in silico generation and augmentation of single-cell RNA-seq data using generative adversarial networks
Authors: Marouf Mohamed , Machart Pierre , Bansal Vikas , Kilian Christoph , Magruder Daniel S. , Krebs Christian F. , Bonn Stefan 
Published: January 2020

AbstractA fundamental problem in biomedical research is the low number of observations available, mostly due to a lack of available biosamples, prohibitive costs, or ethical reasons. Augmenting few real observations with generated in silico samples could lead to more robust analysis results and a higher reproducibility rate. Here, we propose the use of conditional single-cell generative adversarial neural networks (cscGAN) for the realistic generation of single-cell RNA-seq data. cscGAN learns non-linear gene–gene dependencies from complex, multiple cell type samples and uses this information to generate realistic cells of defined types. Augmenting sparse cell populations with cscGAN generated cells improves downstream analyses such as the detection of marker genes, the robustness and reliability of classifiers, the assessment of novel analysis algorithms, and might reduce the number of animal experiments and costs in consequence. cscGAN outperforms existing methods for single-cell RNA-seq data generation in quality and hold great promise for the realistic generation and augmentation of other biomedical data types.
The potential of neurofilaments analysis using dry-blood and plasma spots
Authors: Lombardi Vittoria , Carassiti Daniele , Giovannoni Gavin , Lu Ching-Hua , Adiutori Rocco , Malaspina Andrea 
Published: January 2020

AbstractThe lack of biomarkers for an early diagnosis of neurodegenerative disorders (NDs) has hampered the development of therapeutics whose effect would be enhanced by a timely intervention. Neurofilaments light chain (Nf-L), an integral part of the axonal structure, has emerged as a robust fluid biomarker for fatal neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). To facilitate large-scale studies into early-stage neurodegeneration, reduce costs of samples collection/processing and cold-chain storage, we describe the measurement of Nf-L in blood fractions obtained from dry blood spots (DBS) and dry plasma spots (DPS), two filter paper-based remote blood collection tools. To test the feasibility of using this approach, Nf-L analysis in DBS/DPS is compared to that in plasma obtained from the same blood sample, looking at Nf-L discriminatory power in the clinical stratification of ALS compared to healthy controls. With the best pre-analytical treatment for total protein recovery and using highly sensitive immunoassays, we report the detection of different Nf-L levels in DBS elute compared to reference plasma and DPS from the same blood samples. However, Nf-L measurement in DBS elutes provides a very good discrimination of ALS from healthy controls which is comparable to that obtained using plasma Nf-L assays. With the available immunodetection methods, we show that Nf-L measurement based on DPS microsampling is similar to that in plasma. The filter-paper biophysical characteristics and the interference of high haemoglobin concentration released by erythrocyte lysis is likely to perturb Nf-L detection in DBS elute. Further studies into DBS-based Nf-L detection and its analytical optimization are needed to make this method suitable for routine Nf-L blood analyses in neurodegeneration.