bluuebunny/crossref_metadata_2025_split huggingface dataset:
A transgenerational toxicokinetic model and its use in derivation of Minnesota PFOA water guidance
Authors: Goeden Helen M. , Greene Christopher W. , Jacobus James A. 
Published: January 2019

AbstractMinnesota has been grappling with extensive per- and polyfluoroalkyl substances (PFASs) groundwater contamination since 2002, in a major metropolitan setting. As toxicological information has accumulated for these substances, the public health community has become increasingly aware of critically sensitive populations. The accumulation of some PFAS in women of childbearing age, and the placental and breastmilk transfer to their offspring, require new risk assessment methods to protect public health. The traditional water guidance paradigm is inadequate to address maternal-to-infant transfer of accumulated levels of perfluorooctanoate (PFOA), in particular. Even short exposures during infancy have dramatic impacts on serum levels for many years. In addition, developmental effects are the critical effects anchoring recent risk assessments. In response, the Minnesota Department of Health created an Excel-based model that incorporates chemical-specific properties and exposure parameters for early life stages. Serum levels were assessed in both formula-fed and breastfed infants, with placental transfer in both scenarios. Peak breastfed infant serum levels were 4.4-fold higher than in formula-fed infants, with both of these scenarios producing serum levels in excess of the adult steady-state level. The development and application of this model to PFOA are described.
miR-1254 inhibits cell proliferation, migration, and invasion by down-regulating Smurf1 in gastric cancer
Authors: Jiang Mingkun , Shi Liang , Yang Chao , Ge Yugang , Lin Linling , Fan Hao , He Yu , Zhang Diancai , Miao Yongchang , Yang Li 
Published: January 2019

AbstractGastric cancer (GC) is one of the most frequent malignancies, and increasing evidence supports the contribution of microRNA (miRNAs) to cancer progression. miR-1254 has been confirmed to participate in the regulation of various cancers, while the function of miR-1254 in GC remains unknown. In this study, we investigated the role of miR-1254 in GC. The expression of miR-1254 was detected in human GC specimens and cell lines by miRNA RT-PCR. The effects of miR-1254 on GC proliferation were determined by CCK-8 proliferation assays, colony formation assays, 5-ethynyl-2′-deoxyuridine (EdU) incorporation, and cell-cycle assays. The ability of migration and invasion was examined by transwell and wound-healing assay. Dual Luciferase reporter assay was used to validate the interaction of miR-1254 with its target gene. The xenograft mouse models were conducted to investigate the effects of miR-1254 in vivo. The signaling pathways and epithelial–mesenchymal transition (EMT)-related proteins were detected with western blot. The results showed that miR-1254 inhibited the proliferation, migration and invasion in vitro and suppressed tumorigenesis in vivo. Smurf1 was shown to be the direct target of miR-1254. Overexpressing Smurf1 could partially counteract the effects caused by miR-1254. Similarly, the effects of the miR-1254-inhibitor were also rescued by Smurf1-shRNA. Furthermore, we found that miR-1254 inhibited EMT and decreased the PI3K/AKT signaling pathway through downregulating Smurf1. In summary, overexpression of miR-1254 could suppress proliferation, migration, invasion, and EMT via PI3K/AKT signaling pathways by downregulation of Smurf1 in GC, which suggests a potential therapeutic target for GC.
Newly manufactured Marukome MK-34-1 miso with angiotensin-converting enzyme inhibitory activity and its antihypertensive effects in genetic hypertensive rat models
Authors: Tomari Hiroe Sakuyama , Uchikawa Misa , Yamazaki Aki , Hirabayashi Satomi , Yamakawa Shoko , Kitagawa Manabu , Yamada Minami , Itou Seiki , Yamamoto Tetsuro , Uehara Yoshio 
Published: January 2019

AbstractWe newly manufactured miso rich in angiotensin-converting enzyme (ACE) inhibitory activity (Marukome MK-34-1, shinki miso) and investigated its antihypertensive properties in rat models of genetic hypertension. ACE inhibitory activity was tenfold higher in shinki miso than in commercially available Marukome Nenrin miso (nenrin miso). The inhibitory activity of shinki miso was confined to <3 kDa fractions and was detected in several fractions with high polarity by C18 high-performance liquid chromatography. Systolic blood pressure (SBP) increased age-dependently in stroke-prone spontaneously hypertensive rats (SHRSP/Izm) given a 0.6% (w/v) NaCl solution (salt solution group) that matched the salt content of the miso solutions. This SBP increase was attenuated in both the 5% nenrin and 5% shinki miso solution groups compared to the salt solution group. The reduction in SBP was greater in rats fed shinki than in rats fed nenrin miso. Similarly, in a salt-induced hypertension model with Dahl rats, the 5% nenrin miso solution attenuated the rising SBP observed in the salt solution group. Moreover, combining 5% nenrin miso with 5% shinki miso (2:1, v/v) (awase miso group) significantly decreased the SBP per gram salt intake by 8% compared with the nenrin miso treatment. However, there were no differences in urinary Na excretion between the nenrin and awase miso groups. In conclusion, we produced a new miso with potent ACE inhibitory activity that reduced spontaneous and salt-induced hypertension. These results suggest that salt sensitivity is decreased by the addition of shinki miso to nenrin miso.
How lasing happens in CsPbBr3 perovskite nanowires
Authors: Schlaus Andrew P. , Spencer Michael S. , Miyata Kiyoshi , Liu Fang , Wang Xiaoxia , Datta Ipshita , Lipson Michal , Pan Anlian , Zhu X.-Y. 
Published: January 2019

AbstractLead halide perovskites are emerging as an excellent material platform for optoelectronic processes. There have been extensive discussions on lasing, polariton formation, and nonlinear processes in this material system, but the underlying mechanism remains unknown. Here we probe lasing from CsPbBr3 perovskite nanowires with picosecond (ps) time resolution and show that lasing originates from stimulated emission of an electron-hole plasma. We observe an anomalous blue-shifting of the lasing gain profile with time up to 25 ps, and assign this as a signature for lasing involving plasmon emission. The time domain view provides an ultra-sensitive probe of many-body physics which was obscured in previous time-integrated measurements of lasing from lead halide perovskite nanowires.
The cell cycle regulator GpsB functions as cytosolic adaptor for multiple cell wall enzymes
Authors: Cleverley Robert M. , Rutter Zoe J. , Rismondo Jeanine , Corona Federico , Tsui Ho-Ching Tiffany , Alatawi Fuad A. , Daniel Richard A. , Halbedel Sven , Massidda Orietta , Winkler Malcolm E. , Lewis Richard J. 
Published: January 2019

AbstractBacterial growth and cell division requires precise spatiotemporal regulation of the synthesis and remodelling of the peptidoglycan layer that surrounds the cytoplasmic membrane. GpsB is a cytosolic protein that affects cell wall synthesis by binding cytoplasmic mini-domains of peptidoglycan synthases to ensure their correct subcellular localisation. Here, we describe critical structural features for the interaction of GpsB with peptidoglycan synthases from three bacterial species (Bacillus subtilis, Listeria monocytogenes and Streptococcus pneumoniae) and suggest their importance for cell wall growth and viability in L. monocytogenes and S. pneumoniae. We use these structural motifs to identify novel partners of GpsB in B. subtilis and extend the members of the GpsB interactome in all three bacterial species. Our results support that GpsB functions as an adaptor protein that mediates the interaction between membrane proteins, scaffolding proteins, signalling proteins and enzymes to generate larger protein complexes at specific sites in a bacterial cell cycle-dependent manner.
AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells
Authors: Taniguchi Hirokazu , Yamada Tadaaki , Wang Rong , Tanimura Keiko , Adachi Yuta , Nishiyama Akihiro , Tanimoto Azusa , Takeuchi Shinji , Araujo Luiz H. , Boroni Mariana , Yoshimura Akihiro , Shiotsu Shinsuke , Matsumoto Isao , Watanabe Satoshi , Kikuchi Toshiaki , Miura Satoru , Tanaka Hiroshi , Kitazaki Takeshi , Yamaguchi Hiroyuki , Mukae Hiroshi , Uchino Junji , Uehara Hisanori , Takayama Koichi , Yano Seiji 
Published: January 2019

AbstractA novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells.
Exosomes harbor B cell targets in pancreatic adenocarcinoma and exert decoy function against complement-mediated cytotoxicity
Authors: Capello Michela , Vykoukal Jody V. , Katayama Hiroyuki , Bantis Leonidas E. , Wang Hong , Kundnani Deepali L. , Aguilar-Bonavides Clemente , Aguilar Mitzi , Tripathi Satyendra C. , Dhillon Dilsher S. , Momin Amin A. , Peters Haley , Katz Matthew H. , Alvarez Hector , Bernard Vincent , Ferri-Borgogno Sammy , Brand Randall , Adler Douglas G. , Firpo Matthew A. , Mulvihill Sean J. , Molldrem Jeffrey J. , Feng Ziding , Taguchi Ayumu , Maitra Anirban , Hanash Samir M. 
Published: January 2019

AbstractAlthough B cell response is frequently found in cancer, there is little evidence that it alters tumor development or progression. The process through which tumor-associated antigens trigger humoral response is not well delineated. We investigate the repertoire of antigens associated with humoral immune response in pancreatic ductal adenocarcinoma (PDAC) using in-depth proteomic profiling of immunoglobulin-bound proteins from PDAC patient plasmas and identify tumor antigens that induce antibody response together with exosome hallmark proteins. Additional profiling of PDAC cell-derived exosomes reveals significant overlap in their protein content with immunoglobulin-bound proteins in PDAC plasmas, and significant autoantibody reactivity is observed between PDAC cell-derived exosomes and patient plasmas compared to healthy controls. Importantly, PDAC-derived exosomes induce a dose-dependent inhibition of PDAC serum-mediated complement-dependent cytotoxicity towards cancer cells. In summary, we provide evidence that exosomes display a large repertoire of tumor antigens that induce autoantibodies and exert a decoy function against complement-mediated cytotoxicity.
Regulation of in vivo dynein force production by CDK5 and 14-3-3ε and KIAA0528
Authors: Chapman Dail E. , Reddy Babu J. N. , Huy Bunchhin , Bovyn Matthew J. , Cruz Stephen John S. , Al-Shammari Zahraa M. , Han Han , Wang Wenqi , Smith Deanna S. , Gross Steven P. 
Published: January 2019

AbstractSingle-molecule cytoplasmic dynein function is well understood, but there are major gaps in mechanistic understanding of cellular dynein regulation. We reported a mode of dynein regulation, force adaptation, where lipid droplets adapt to opposition to motion by increasing the duration and magnitude of force production, and found LIS1 and NudEL to be essential. Adaptation reflects increasing NudEL-LIS1 utilization; here, we hypothesize that such increasing utilization reflects CDK5-mediated NudEL phosphorylation, which increases the dynein-NudEL interaction, and makes force adaptation possible. We report that CDK5, 14-3-3ε, and CDK5 cofactor KIAA0528 together promote NudEL phosphorylation and are essential for force adaptation. By studying the process in COS-1 cells lacking Tau, we avoid confounding neuronal effects of CDK5 on microtubules. Finally, we extend this in vivo regulatory pathway to lysosomes and mitochondria. Ultimately, we show that dynein force adaptation can control the severity of lysosomal tug-of-wars among other intracellular transport functions involving high force.
The HisCl1 histamine receptor acts in photoreceptors to synchronize Drosophila behavioral rhythms with light-dark cycles
Authors: Alejevski Faredin , Saint-Charles Alexandra , Michard-Vanhée Christine , Martin Béatrice , Galant Sonya , Vasiliauskas Daniel , Rouyer François 
Published: January 2019

AbstractIn Drosophila, the clock that controls rest-activity rhythms synchronizes with light-dark cycles through either the blue-light sensitive cryptochrome (Cry) located in most clock neurons, or rhodopsin-expressing histaminergic photoreceptors. Here we show that, in the absence of Cry, each of the two histamine receptors Ort and HisCl1 contribute to entrain the clock whereas no entrainment occurs in the absence of the two receptors. In contrast to Ort, HisCl1 does not restore entrainment when expressed in the optic lobe interneurons. Indeed, HisCl1 is expressed in wild-type photoreceptors and entrainment is strongly impaired in flies with photoreceptors mutant for HisCl1. Rescuing HisCl1 expression in the Rh6-expressing photoreceptors restores entrainment but it does not in other photoreceptors, which send histaminergic inputs to Rh6-expressing photoreceptors. Our results thus show that Rh6-expressing neurons contribute to circadian entrainment as both photoreceptors and interneurons, recalling the dual function of melanopsin-expressing ganglion cells in the mammalian retina.
Recurrent activating mutations of PPARγ associated with luminal bladder tumors
Authors: Rochel Natacha , Krucker Clémentine , Coutos-Thévenot Laure , Osz Judit , Zhang Ruiyun , Guyon Elodie , Zita Wayne , Vanthong Séverin , Hernandez Oscar Alba , Bourguet Maxime , Badawy Kays Al , Dufour Florent , Peluso-Iltis Carole , Heckler-Beji Syrine , Dejaegere Annick , Kamoun Aurélie , de Reyniès Aurélien , Neuzillet Yann , Rebouissou Sandra , Béraud Claire , Lang Hervé , Massfelder Thierry , Allory Yves , Cianférani Sarah , Stote Roland H. , Radvanyi François , Bernard-Pierrot Isabelle 
Published: January 2019

AbstractThe upregulation of PPARγ/RXRα transcriptional activity has emerged as a key event in luminal bladder tumors. It renders tumor cell growth PPARγ-dependent and modulates the tumor microenvironment to favor escape from immuno-surveillance. The activation of the pathway has been linked to PPARG gains/amplifications resulting in PPARγ overexpression and to recurrent activating point mutations of RXRα. Here, we report recurrent mutations of PPARγ that also activate the PPARγ/RXRα pathway, conferring PPARγ-dependency and supporting a crucial role of PPARγ in luminal bladder cancer. These mutations are found throughout the protein—including N-terminal, DNA-binding and ligand-binding domains—and most of them enhance protein activity. Structure-function studies of PPARγ variants with mutations in the ligand-binding domain allow identifying structural elements that underpin their gain-of-function. Our study reveals genomic alterations of PPARG that lead to pro-tumorigenic PPARγ/RXRα pathway activation in luminal bladder tumors and may open the way towards alternative options for treatment.
A unifying framework for interpreting and predicting mutualistic systems
Authors: Wu Feilun , Lopatkin Allison J. , Needs Daniel A. , Lee Charlotte T. , Mukherjee Sayan , You Lingchong 
Published: January 2019

AbstractCoarse-grained rules are widely used in chemistry, physics and engineering. In biology, however, such rules are less common and under-appreciated. This gap can be attributed to the difficulty in establishing general rules to encompass the immense diversity and complexity of biological systems. Furthermore, even when a rule is established, it is often challenging to map it to mechanistic details and to quantify these details. Here we report a framework that addresses these challenges for mutualistic systems. We first deduce a general rule that predicts the various outcomes of mutualistic systems, including coexistence and productivity. We further develop a standardized machine-learning-based calibration procedure to use the rule without the need to fully elucidate or characterize their mechanistic underpinnings. Our approach consistently provides explanatory and predictive power with various simulated and experimental mutualistic systems. Our strategy can pave the way for establishing and implementing other simple rules for biological systems.
Image-based modeling of kidney branching morphogenesis reveals GDNF-RET based Turing-type mechanism and pattern-modulating WNT11 feedback
Authors: Menshykau Denis , Michos Odyssé , Lang Christine , Conrad Lisa , McMahon Andrew P. , Iber Dagmar 
Published: January 2019

AbstractBranching patterns and regulatory networks differ between branched organs. It has remained unclear whether a common regulatory mechanism exists and how organ-specific patterns can emerge. Of all previously proposed signalling-based mechanisms, only a ligand-receptor-based Turing mechanism based on FGF10 and SHH quantitatively recapitulates the lung branching patterns. We now show that a GDNF-dependent ligand-receptor-based Turing mechanism quantitatively recapitulates branching of cultured wildtype and mutant ureteric buds, and achieves similar branching patterns when directing domain outgrowth in silico. We further predict and confirm experimentally that the kidney-specific positive feedback between WNT11 and GDNF permits the dense packing of ureteric tips. We conclude that the ligand-receptor based Turing mechanism presents a common regulatory mechanism for lungs and kidneys, despite the differences in the molecular implementation. Given its flexibility and robustness, we expect that the ligand-receptor-based Turing mechanism constitutes a likely general mechanism to guide branching morphogenesis and other symmetry breaks during organogenesis.
Planar and van der Waals heterostructures for vertical tunnelling single electron transistors
Authors: Kim Gwangwoo , Kim Sung-Soo , Jeon Jonghyuk , Yoon Seong In , Hong Seokmo , Cho Young Jin , Misra Abhishek , Ozdemir Servet , Yin Jun , Ghazaryan Davit , Holwill Matthew , Mishchenko Artem , Andreeva Daria V. , Kim Yong-Jin , Jeong Hu Young , Jang A-Rang , Chung Hyun-Jong , Geim Andre K. , Novoselov Kostya S. , Sohn Byeong-Hyeok , Shin Hyeon Suk 
Published: January 2019

AbstractDespite a rich choice of two-dimensional materials, which exists these days, heterostructures, both vertical (van der Waals) and in-plane, offer an unprecedented control over the properties and functionalities of the resulted structures. Thus, planar heterostructures allow p-n junctions between different two-dimensional semiconductors and graphene nanoribbons with well-defined edges; and vertical heterostructures resulted in the observation of superconductivity in purely carbon-based systems and realisation of vertical tunnelling transistors. Here we demonstrate simultaneous use of in-plane and van der Waals heterostructures to build vertical single electron tunnelling transistors. We grow graphene quantum dots inside the matrix of hexagonal boron nitride, which allows a dramatic reduction of the number of localised states along the perimeter of the quantum dots. The use of hexagonal boron nitride tunnel barriers as contacts to the graphene quantum dots make our transistors reproducible and not dependent on the localised states, opening even larger flexibility when designing future devices.
Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy
Authors: Wu Qing , He Zhigang , Wang Xia , Zhang Qi , Wei Qingcong , Ma Sunqiang , Ma Cheng , Li Jiyu , Wang Qigang 
Published: January 2019

AbstractAs the first line of innate immune cells to migrate towards tumour tissue, neutrophils, can immediately kill abnormal cells and activate long-term specific adaptive immune responses. Therefore, the enzymes mediated elevation of reactive oxygen species (ROS) bioinspired by neutrophils can be a promising strategy in cancer immunotherapy. Here, we design a core-shell supramolecular hybrid nanogel via the surface phosphatase triggered self-assembly of oligopeptides around iron oxide nanoparticles to simulate productive neutrophil lysosomes. The cascade reaction of superoxide dismutase (SOD) and chloroperoxidase (CPO) within the bioinspired nanogel can convert ROS in tumour tissue to hypochlorous acid (HOCl) and the subsequent singlet oxygen (1O2) species. Studies on both cells and animals demonstrate successful 1O2-mediated cell/tumour proliferation inhibition, making this enzyme therapy capable for treating tumours without external energy activation.
Study on the scheme design of integrated grounding system for a 550 kV gas insulated transmission line
Authors: Zhao Chun , Tang Liangliang , Huang Daochun , Xia Jun , Liu Xi , Xu Xia 
Published: January 2019

Gas insulated transmission line (GIL) is an advanced power transmission mode. Since the extension of this kind of equipment is relatively long, the grounding design and layout of the GIL will have a direct impact on personal safety and the stability operation of equipment, which should be given full attention. In order to ensure the safe and stable operation of GIL, it needs reasonably design and arrangement of the integrated grounding system in the GIL pipelines. This study designed corresponding grounding scheme for the integrated grounding system of underground GIL pipelines combined with a 550 kV/4000 A GIL. The corresponding simulation model of the integrated grounding system was established with specific parameters of the GIL. The calculation results show that the grounding resistance of the integrated grounding system is 0.217 Ω, which is less than the grounding requirement value of 1 Ω, and it reduces 28.9% compared with the simulation model without considering the natural grounding body. In addition, the step voltage and touch voltage are reduced by 79.91 and 48.97%, respectively. The research results can give some references for the integrated grounding system design of GIL engineering.
Application of 500 kV UPFC in Suzhou southern power grid
Authors: Wang Xu , Wang Haiqian , Yang Jian , Xu Zheng , Sun Wentao , Wu Chen , Li Chen 
Published: January 2019

The implementation of a 500 kV unified power flow controller (UPFC) project in Suzhou southern power grid is reported in this study. The UPFC project has been put into operation at the end of 2017, and has become the largest capacity and highest voltage‐level UPFC in the world. The overview of the Suzhou southern power grid is first introduced. The challenges of the grid, such as the limited transmission capability and the insufficient reactive power supply, are also demonstrated. Great technical and economic difficulties have to be overcome for the implementation of traditional solutions, so an attempt of the UPFC scheme is put forward. The UPFC scheme is introduced in detail, including the topology structure, the main equipment selection, the expected effect, the implementation difficulties and the investment. It is shown that the 500 kV UPFC project is more economical and feasible than the traditional solutions. The operation problems of the Suzhou southern power grid will be alleviated effectively by the UPFC project. Besides, this project is of much demonstration value to the application of high‐voltage‐level and large rating UPFC projects.