bluuebunny/crossref_metadata_2025_split huggingface dataset:
p53 β-hydroxybutyrylation attenuates p53 activity
Authors: Liu Kun , Li Fangzhou , Sun Qianqian , Lin Ning , Han Haichao , You Kaiqiang , Tian Feng , Mao Zebin , Li Tingting , Tong Tanjun , Geng Meiyu , Zhao Yingming , Gu Wei , Zhao Wenhui 
Published: March 2019

Abstractp53 is an essential tumor suppressor, whose activity is finely tuned by the posttranslational modifications. Previous research has reported that β-hydroxybutyrate (BHB) induces β-hydroxybutyrylation (Kbhb), which is a novel histone posttranslational modification. Here we report that p53 is modified by kbhb and that this modification occurs at lysines 120, 319, and 370 of p53. We demonstrate that the level of p53 kbhb is dramatically increased in cultured cells treated with BHB and in thymus tissues of fasted mice, and that CBP catalyze p53 kbhb. We show that p53 kbhb results in lower levels of p53 acetylation and reduced expression of the p53 downstream genes p21 and PUMA, as well as reduced cell growth arrest and apoptosis in cultured cells under p53-activating conditions. Similar results were observed in mouse thymus tissue under starvation conditions, which result in increased concentrations of serum BHB, and in response to genotoxic stress caused by γ-irradiation to activate p53. Our findings thus show that BHB-mediated p53 kbhb is a novel mechanism of p53 activity regulation, which may explain the link between ketone bodies and tumor, and which may provide promising therapeutic target for cancer treatment.
SOX12 promotes colorectal cancer cell proliferation and metastasis by regulating asparagine synthesis
Authors: Du Feng , Chen Jie , Liu Hao , Cai Yanhui , Cao Tianyu , Han Weili , Yi Xiaofang , Qian Meirui , Tian Dean , Nie Yongzhan , Wu Kaichun , Fan Daiming , Xia Limin 
Published: March 2019

AbstractThe sex-determining region Y (SRY)-box (SOX) family has a crucial role in carcinogenesis and cancer progression. However, the role of SOX12 and the mechanism by which it is dysregulated in colorectal cancer (CRC) remain unclear. Here we analyzed SOX12 expression patterns in two independent CRC cohorts (cohort I, n = 390; cohort II, n = 363) and found that SOX12 was significantly upregulated in CRC, indicating a poor prognosis in CRC patients. Overexpression of SOX12 promoted CRC cell proliferation and metastasis, whereas downregulation of SOX12 hampered CRC aggressiveness. Mechanistically, SOX12 facilitated asparagine synthesis by transactivating glutaminase (GLS), glutamic oxaloacetic transaminase 2 (GOT2), and asparagine synthetase (ASNS). Downregulation of GLS, GOT2, and ASNS blocked SOX12-mediated CRC cell proliferation and metastasis, whereas ectopic expression of GLS, GOT2, and ASNS attenuated the SOX12 knockdown-induced suppression of CRC progression. In addition, serial deletion, site-directed mutagenesis, luciferase reporter, and chromatin immunoprecipitation (ChIP) assays indicated that hypoxia-inducible factor 1α (HIF-1α) directly binds to the SOX12 promoter and induces SOX12 expression. Administration of l-asparaginase decreased SOX12-mediated tumor growth and metastasis. In human CRC samples, SOX12 expression positively correlated with GLS, GOT2, ASNS, and HIF-1α expression. Based on these results, SOX12 may serve as a prognostic biomarker and l-asparaginase represents a potential novel therapeutic agent for CRC.
Sweat gland organoids contribute to cutaneous wound healing and sweat gland regeneration
Authors: Diao Jinmei , Liu Juan , Wang Shuyong , Chang Mingyang , Wang Xuan , Guo Baolin , Yu Qunfang , Yan Fang , Su Yuxin , Wang Yunfang 
Published: March 2019

AbstractSweat glands perform a vital thermoregulatory function in mammals. Like other skin components, they originate from epidermal progenitors. However, they have low regenerative potential in response to injury. We have established a sweat gland culture and expansion method using 3D organoids cultures. The epithelial cells derived from sweat glands in dermis of adult mouse paw pads were embedded into Matrigel and formed sweat gland organoids (SGOs). These organoids maintained remarkable stem cell features and demonstrated differentiation capacity to give rise to either sweat gland cells (SGCs) or epidermal cells. Moreover, the bipotent SGO-derived cells could be induced into stratified epidermis structures at the air−liquid interface culture in a medium tailored for skin epidermal cells in vitro. The SGCs embedded in Matrigel tailored for sweat glands formed epithelial organoids, which expressed sweat-gland-specific markers, such as cytokeratin (CK) 18 and CK19, aquaporin (AQP) 5 and αATP. More importantly, they had potential of regeneration of epidermis and sweat gland when they were transplanted into the mouse back wound and claw pad with sweat gland injury, respectively. In summary, we established and optimized culture conditions for effective generation of mouse SGOs. These cells are candidates to restore impaired sweat gland tissue as well as to improve cutaneous skin regeneration.
Low-dose 2-deoxyglucose and metformin synergically inhibit proliferation of human polycystic kidney cells by modulating glucose metabolism
Authors: Zhao Jing , Ma Yuxiang , Zhang Yingjie , Fu Bo , Wu Xiaoyuan , Li Qinggang , Cai Guangyan , Chen Xiangmei , Bai Xue-Yuan 
Published: March 2019

AbstractPolycystic kidney disease (PKD) is a common hereditary kidney disease with abnormal proliferation and apoptosis of kidney cystic epithelial cells, eventually leading to chronic renal failure. Currently, there are no effective treatment methods. Similar to tumor cells, cystic epithelial cells have abnormal glycolysis and over-activation of proliferation signaling pathways. In the present study, for the first time, we investigated the effects of low-dose combinational use of 2-deoxyglucose (2-DG) and metformin (MET) on the proliferation and apoptosis in the human cystic kidney epithelial cells. Cystic epithelia cells were divided into control group, 2-DG group, MET group and 2-DG+MET group. Cell Proliferation, apoptosis and glucose metabolism were measured in each group. The results showed that low-dose combinational treatment of 2-DG and MET significantly inhibited the proliferation of renal cystic epithelial cells by suppressing the activities of PKA, mTOR and ERK signaling pathways and upregulating PI3K/Akt pathway. Combination of both drugs increased the apoptosis rates of cystic epithelial cells. Two drugs inhibited glucose metabolic phenotypes, glycolysis and oxidative phosphorylation, and significantly lowered the intracellular ATP level in cystic epithelial cells. 2-DG could also neutralize excessive production of lactate (lactic acidosis) caused by MET and both drugs had complementary effect for cystic epithelial cells. These results reveal that combinational use of low-dose 2-DG and MET can markedly inhibit proliferation via modulating glucose metabolic phenotypes in human polycystic kidney epithelial cells, low-dose combinational use of both drugs can also lower the toxic effects of each drug, and is a novel strategy for future treatment of human polycystic kidney disease.
Observation of dressed states of distant atoms with delocalized photons in coupled-cavities quantum electrodynamics
Authors: Kato Shinya , Német Nikolett , Senga Kohei , Mizukami Shota , Huang Xinhe , Parkins Scott , Aoki Takao 
Published: March 2019

AbstractIn a cavity quantum electrodynamics (QED) system, where atoms coherently interact with photons in a cavity, the eigenstates of the system are the superposition states of atoms and cavity photons, the so-called dressed states of atoms. When two cavities are connected by an optical fiber with negligible loss, the coherent coupling between the cavities gives rise to photonic normal modes. One of these normal modes is the fiber-dark mode, in which photons are delocalized in the two distant cavities. Here we demonstrate the setting of coupled-cavities QED, where two nanofiber cavity-QED systems are coherently connected by a meter-long low-loss channel in an all-fiber fashion. Specifically, we observe dressed states of distant atoms with delocalized photons of the fiber-dark normal mode. Our system will provide a platform for the study of delocalized atomic and photonic states, photonic many-body physics, and distributed quantum computation.
Unmasking Clever Hans predictors and assessing what machines really learn
Authors: Lapuschkin Sebastian , Wäldchen Stephan , Binder Alexander , Montavon Grégoire , Samek Wojciech , Müller Klaus-Robert 
Published: March 2019

AbstractCurrent learning machines have successfully solved hard application problems, reaching high accuracy and displaying seemingly intelligent behavior. Here we apply recent techniques for explaining decisions of state-of-the-art learning machines and analyze various tasks from computer vision and arcade games. This showcases a spectrum of problem-solving behaviors ranging from naive and short-sighted, to well-informed and strategic. We observe that standard performance evaluation metrics can be oblivious to distinguishing these diverse problem solving behaviors. Furthermore, we propose our semi-automated Spectral Relevance Analysis that provides a practically effective way of characterizing and validating the behavior of nonlinear learning machines. This helps to assess whether a learned model indeed delivers reliably for the problem that it was conceived for. Furthermore, our work intends to add a voice of caution to the ongoing excitement about machine intelligence and pledges to evaluate and judge some of these recent successes in a more nuanced manner.
Exploring the ternary interactions in Cu–ZnO–ZrO2 catalysts for efficient CO2 hydrogenation to methanol
Authors: Wang Yuhao , Kattel Shyam , Gao Wengui , Li Kongzhai , Liu Ping , Chen Jingguang G. , Wang Hua 
Published: March 2019

AbstractThe synergistic interaction among different components in complex catalysts is one of the crucial factors in determining catalytic performance. Here we report the interactions among the three components in controlling the catalytic performance of Cu–ZnO–ZrO2 (CZZ) catalyst for CO2 hydrogenation to methanol. The in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) measurements under the activity test pressure (3 MPa) reveal that the CO2 hydrogenation to methanol on the CZZ catalysts follows the formate pathway. Density functional theory (DFT) calculations agree with the in situ DRIFTS measurements, showing that the ZnO–ZrO2 interfaces are the active sites for CO2 adsorption and conversion, while the presence of metallic Cu is also necessary to facilitate H2 dissociation and to provide hydrogen resource. The combined experiment and DFT results reveal that tuning the interaction between ZnO and ZrO2 can be considered as another important factor for designing high performance catalysts for methanol generation from CO2.
Ultrafast photonic micro-systems to manipulate hard X-rays at 300 picoseconds
Authors: Chen Pice , Jung Il Woong , Walko Donald A. , Li Zhilong , Gao Ya , Shenoy Gopal K. , López Daniel , Wang Jin 
Published: March 2019

AbstractTime-resolved and ultrafast hard X-ray imaging, scattering and spectroscopy are powerful tools for elucidating the temporal and spatial evolution of complexity in materials. However, their temporal resolution has been limited by the storage-ring timing patterns and X-ray pulse width at synchrotron sources. Here we demonstrate that dynamic X-ray optics based on micro-electro-mechanical-system resonators can manipulate hard X-ray pulses on time scales down to 300 ps, comparable to the X-ray pulse width from typical synchrotron sources. This is achieved by timing the resonators with the storage ring to diffract X-ray pulses through the narrow Bragg peak of the single-crystalline material. Angular velocities exceeding 107degrees s−1are reached while maintaining the maximum linear velocity well below the sonic speed and material breakdown limit. As the time scale of the devices shortens, the devices promise to spatially disperse the temporal width of X-rays, thus generating a temporal resolution below the pulse-width limit.
A late B lymphocyte action in dysfunctional tissue repair following kidney injury and transplantation
Authors: Cippà Pietro E. , Liu Jing , Sun Bo , Kumar Sanjeev , Naesens Maarten , McMahon Andrew P. 
Published: March 2019

AbstractThe mechanisms initiating late immune responses to an allograft are poorly understood. Here we show, via transcriptome analysis of serial protocol biopsies from kidney transplants, that the initial responses to kidney injury correlate with a late B lymphocyte signature relating to renal dysfunction and fibrosis. With a potential link between dysfunctional repair and immunoreactivity, we investigate the immunological consequences of dysfunctional repair examining chronic disease in mouse kidneys 18 months after a bilateral ischemia/reperfusion injury event. In the absence of foreign antigens, a sustained immune response involving both innate and adaptive immune systems accompanies a transition to chronic kidney damage. At late stages, B lymphocytes exhibite an antigen-driven proliferation, selection and maturation into broadly-reacting antibody-secreting cells. These findings reveal a previously unappreciated role for dysfunctional tissue repair in local immunomodulation that may have particular relevance to transplant-associated immunobiology.
Structural basis for transcription initiation by bacterial ECF σ factors
Authors: Li Lingting , Fang Chengli , Zhuang Ningning , Wang Tiantian , Zhang Yu 
Published: March 2019

AbstractBacterial RNA polymerase employs extra-cytoplasmic function (ECF) σ factors to regulate context-specific gene expression programs. Despite being the most abundant and divergent σ factor class, the structural basis of ECF σ factor-mediated transcription initiation remains unknown. Here, we determine a crystal structure of Mycobacterium tuberculosis (Mtb) RNAP holoenzyme comprising an RNAP core enzyme and the ECF σ factor σH (σH-RNAP) at 2.7 Å, and solve another crystal structure of a transcription initiation complex of Mtb σH-RNAP (σH-RPo) comprising promoter DNA and an RNA primer at 2.8 Å. The two structures together reveal the interactions between σH and RNAP that are essential for σH-RNAP holoenzyme assembly as well as the interactions between σH-RNAP and promoter DNA responsible for stringent promoter recognition and for promoter unwinding. Our study establishes that ECF σ factors and primary σ factors employ distinct mechanisms for promoter recognition and for promoter unwinding.
A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma
Authors: Syafruddin Saiful E. , Rodrigues Paulo , Vojtasova Erika , Patel Saroor A. , Zaini M. Nazhif , Burge Johanna , Warren Anne Y. , Stewart Grant D. , Eisen Tim , Bihary Dóra , Samarajiwa Shamith A. , Vanharanta Sakari 
Published: March 2019

AbstractTranscriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of the zinc finger family, regulates lipid homeostasis in clear cell renal cell carcinoma (ccRCC). We show that KLF6 supports the expression of lipid metabolism genes and promotes the expression of PDGFB, which activates mTOR signalling and the downstream lipid metabolism regulators SREBF1 and SREBF2. KLF6 expression is driven by a robust super enhancer that integrates signals from multiple pathways, including the ccRCC-initiating VHL-HIF2A pathway. These results suggest an underlying mechanism for high mTOR activity in ccRCC cells. More generally, the link between super enhancer-driven transcriptional networks and essential metabolic pathways may provide clues to the mechanisms that maintain the stability of cell identity-defining transcriptional programmes in cancer.
Whole-genome resequencing reveals Brassica napus origin and genetic loci involved in its improvement
Authors: Lu Kun , Wei Lijuan , Li Xiaolong , Wang Yuntong , Wu Jian , Liu Miao , Zhang Chao , Chen Zhiyou , Xiao Zhongchun , Jian Hongju , Cheng Feng , Zhang Kai , Du Hai , Cheng Xinchao , Qu Cunming , Qian Wei , Liu Liezhao , Wang Rui , Zou Qingyuan , Ying Jiamin , Xu Xingfu , Mei Jiaqing , Liang Ying , Chai You-Rong , Tang Zhanglin , Wan Huafang , Ni Yu , He Yajun , Lin Na , Fan Yonghai , Sun Wei , Li Nan-Nan , Zhou Gang , Zheng Hongkun , Wang Xiaowu , Paterson Andrew H. , Li Jiana 
Published: March 2019

AbstractBrassica napus (2n = 4x = 38, AACC) is an important allopolyploid crop derived from interspecific crosses between Brassica rapa (2n = 2x = 20, AA) and Brassica oleracea (2n = 2x = 18, CC). However, no truly wild B. napus populations are known; its origin and improvement processes remain unclear. Here, we resequence 588 B. napus accessions. We uncover that the A subgenome may evolve from the ancestor of European turnip and the C subgenome may evolve from the common ancestor of kohlrabi, cauliflower, broccoli, and Chinese kale. Additionally, winter oilseed may be the original form of B. napus. Subgenome-specific selection of defense-response genes has contributed to environmental adaptation after formation of the species, whereas asymmetrical subgenomic selection has led to ecotype change. By integrating genome-wide association studies, selection signals, and transcriptome analyses, we identify genes associated with improved stress tolerance, oil content, seed quality, and ecotype improvement. They are candidates for further functional characterization and genetic improvement of B. napus.
A chemically inert bismuth interlayer enhances long-term stability of inverted perovskite solar cells
Authors: Wu Shaohang , Chen Rui , Zhang Shasha , Babu B. Hari , Yue Youfeng , Zhu Hongmei , Yang Zhichun , Chen Chuanliang , Chen Weitao , Huang Yuqian , Fang Shaoying , Liu Tianlun , Han Liyuan , Chen Wei 
Published: March 2019

AbstractLong-term stability remains a key issue impeding the commercialization of halide perovskite solar cells (HPVKSCs). The diffusion of molecules and ions causes irreversible degradation to photovoltaic device performance. Here, we demonstrate a facile strategy for producing highly stable HPVKSCs by using a thin but compact semimetal Bismuth interlayer. The Bismuth film acts as a robust permeation barrier that both insulates the perovskite from intrusion by undesirable external moisture and protects the metal electrode from iodine corrosion. The Bismuth-interlayer-based devices exhibit greatly improved stability when subjected to humidity, thermal and light stresses. The unencapsulated device retains 88% of its initial efficiency in ambient air in the dark for over 6000 h; the devices maintain 95% and 97% of their initial efficiencies after 85 °C thermal aging and light soaking in nitrogen atmosphere for 500 h, respectively. These sound stability parameters are among the best for planar structured HPVKSCs reported to date.
Essential biodiversity variables for mapping and monitoring species populations
Authors: Jetz Walter , McGeoch Melodie A. , Guralnick Robert , Ferrier Simon , Beck Jan , Costello Mark J. , Fernandez Miguel , Geller Gary N. , Keil Petr , Merow Cory , Meyer Carsten , Muller-Karger Frank E. , Pereira Henrique M. , Regan Eugenie C. , Schmeller Dirk S. , Turak Eren 
Published: March 2019

AbstractSpecies distributions and abundances are undergoing rapid changes worldwide. This highlights the significance of reliable, integrated information for guiding and assessing actions and policies aimed at managing and sustaining the many functions and benefits of species. Here we synthesize the types of data and approaches that are required to achieve such an integration and conceptualize ‘essential biodiversity variables’ (EBVs) for a unified global capture of species populations in space and time. The inherent heterogeneity and sparseness of raw biodiversity data are overcome by the use of models and remotely sensed covariates to inform predictions that are contiguous in space and time and global in extent. We define the species population EBVs as a space–time–species–gram (cube) that simultaneously addresses the distribution or abundance of multiple species, with its resolution adjusted to represent available evidence and acceptable levels of uncertainty. This essential information enables the monitoring of single or aggregate spatial or taxonomic units at scales relevant to research and decision-making. When combined with ancillary environmental or species data, this fundamental species population information directly underpins a range of biodiversity and ecosystem function indicators. The unified concept we present links disparate data to downstream uses and informs a vision for species population monitoring in which data collection is closely integrated with models and infrastructure to support effective biodiversity assessment.
Mesoporous Platinum Prepared by Electrodeposition for Ultralow Loading Proton Exchange Membrane Fuel Cells
Authors: Paul Michael T. Y. , Gates Byron D. 
Published: March 2019

AbstractThe porosity and utilization of platinum catalysts have a direct impact on their performance within proton exchange membrane fuel cells. It is desirable to identify methods that can prepare these catalysts with the desired features, and that can be widely implemented using existing and industrially scalable techniques. Through the use of electrodeposition processes, fuel cell testing, and electron microscopy analyses before and after fuel cell testing, we report the preparation and performance of mesoporous platinum catalysts for proton exchange membrane fuel cells. We found that these mesoporous platinum catalysts can be prepared in sufficient quantities through techniques that also enable their direct incorporation into membrane electrode assemblies. We also determined that the mesoporous catalysts achieved a high porosity, which was retained after assembly and utilization within fuel cells. In addition, these mesoporous platinum catalysts exhibited an improved platinum mass specific power over catalysts prepared from commercially available platinum nanocatalysts.
USP18 and ISG15 coordinately impact on SKP2 and cell cycle progression
Authors: Vuillier Françoise , Li Zhi , Commere Pierre-Henri , Dynesen Lasse Toftdal , Pellegrini Sandra 
Published: March 2019

AbstractUSP18 is an isopeptidase that cleaves the ubiquitin-like ISG15 from conjugates and is also an essential negative feedback regulator of type I interferon signaling. We and others reported that USP18 protein is stabilized by ISG15 and targeted for degradation by SKP2 (S-phase kinase associated protein 2), the substrate-recognition subunit of the SCFSKP2 ubiquitin E3 ligase complex, which operates in cell cycle progression. Here, we have analyzed how, under non stimulated conditions, USP18, ISG15 and SKP2 communicate with each other, by enforcing or silencing their expression. We found that USP18 and SKP2 interact and that free ISG15 abrogates the complex, liberating USP18 from degradation and concomitantly driving SKP2 to degradation and/or ISGylation. These data reveal a dynamic interplay where the substrate USP18 stabilizes SKP2, both exogenous and endogenous. Consistent with this we show that silencing of baseline USP18 slows down progression of HeLa S3 cells towards S phase. Our findings point to USP18 and ISG15 as unexpected new SKP2 regulators, which aid in cell cycle progression at homeostasis.