bluuebunny/crossref_metadata_2025_split huggingface dataset:
SVIP alleviates CCl4-induced liver fibrosis via activating autophagy and protecting hepatocytes
Authors: Jia Dan , Wang Yuan Yuan , Wang Pin , Huang Yao , Liang David Yuke , Wang Dongmei , Cheng Chuandong , Zhang Caihua , Guo Lianying , Liang Pin , Wang Yang , Jia Yujie , Li Cong 
Published: January 2019

AbstractProlonged parenchymal cell death leads to activation of fibrogenic cells and extracellular matrix accumulation and eventually liver fibrosis. Autophagy, a major catabolic process of intracellular degradation and recycling, participates in hepatic fibrosis. However, the precise role of autophagy in the pathogenesis of hepatic fibrosis is controversial. The present study aims to investigate the key role of small VCP/p97 interacting protein (SVIP) against CCl4-induced hepatic fibrosis via activating autophagy. Autophagy could be activated by SVIP in HepG2 cells, but starvation cannot increase SVIP expression in vitro and in vivo. Moreover, SVIP expression, in agreement with autophagic activity and the volume of lipid droplets, first increases and then decreases during the progression of liver fibrosis with CCl4 treatment in vivo and in vivo. Further, overexpression of SVIP can protect HepG2 cells from the toxicity of CCl4, which could be enhanced by starvation. Finally, starvation keeps SVIP and autophagy at such high levels in the rat livers that markedly delays the progress of hepatic fibrosis. Probably, the protective effect of SVIP is associated with stabilizing nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) and transcription factor EB (TFEB). The current study provides insight into the biological role of SVIP and autophagy in regulating hepatic fibrosis, targeting SVIP might be a novel therapeutic strategy in the future.
Cereblon attenuates DNA damage-induced apoptosis by regulating the transcription-independent function of p53
Authors: Zhou Liang , Xu Guoqiang 
Published: January 2019

AbstractCereblon (CRBN) is the substrate receptor of the cullin 4-RING E3 ligase complex and has been employed for targeted protein degradation in the treatment of cancers. However, its normal physiological functions and molecular mechanism in the regulation of DNA damage response are largely unknown. Here we find that CRBN plays a protective role against DNA damage-induced apoptosis in cell lines and primary cells. Mechanistic studies demonstrate that although CRBN does not affect the ubiquitination and degradation of the tumor suppressor p53, it directly interacts with p53 and therefore, suppresses the interaction between p53 and anti-apoptotic regulators Bcl-2 and Bcl-XL. CRBN depletion enhances the interaction between p53 and Bcl-2/Bcl-XL, reduces mitochondrial membrane potential, increases the cleavage of caspase-3 and poly(ADP-ribose) polymerase 1, and thus promotes DNA damage-induced apoptosis in cell lines and primary cells upon etoposide treatment. Moreover, Crbn knockout mice exhibit increased mortality upon etoposide challenge. Taken together, our data elucidate a novel molecular mechanism by which CRBN inhibits DNA damage response in vitro and in vivo. This work extends our understanding of the broad spectrum of physiological roles for CRBN and may suggest its potential application in the treatment of DNA damage-associated diseases.
SHROOM2 inhibits tumor metastasis through RhoA–ROCK pathway-dependent and -independent mechanisms in nasopharyngeal carcinoma
Authors: Yuan Jing , Chen Lin , Xiao Jingshu , Qi Xue-Kang , Zhang Ji , Li Xu , Wang Zifeng , Lian Yi-Fan , Xiang Tong , Zhang Yuchen , Chen Ming-Yuan , Bei Jin-Xin , Zeng Yi-Xin , Feng Lin 
Published: January 2019

AbstractSHROOM2 is a key mediator of RhoA–ROCK pathway that regulates cell motility and actin cytoskeleton organization. However, the functions of SHROOM2 beyond RhoA/ROCK signaling remain poorly understood. Here, we report that SHROOM2 not only participates in RhoA–ROCK-induced stress fiber formation and focal adhesion, but also had an unanticipated role in suppressing epithelial-to-mesenchymal transition (EMT) and tumor metastasis. Depletion of SHROOM2 in nasopharyngeal carcinoma (NPC) cells enhances mesenchymal characteristics and reduces epithelial markers, concomitant with increased motility, enabling the development of invasion and tumor metastasis, which are largely ROCK-independent, as ROCK inhibitor Y-27632 did not cause EMT phenotype; furthermore, combination of ROCK inhibition and SHROOM2 depletion resulted in the most robust increases in cell migration and invasion, indicating that SHROOM2 and ROCK work synergistically rather than epistatic. Analysis of clinical samples suggested that SHROOM2 is downregulated in NPC and the expression of SHROOM2 in metastatic NPC was even lower than in the primary tumors. Our findings uncover a non-canonical role of SHROOM2 as a potent antagonist for EMT and NPC metastasis.
The pivotal role of protein acetylation in linking glucose and fatty acid metabolism to β-cell function
Authors: Zhang Yuqing , Zhou Feiye , Bai Mengyao , Liu Yun , Zhang Linlin , Zhu Qin , Bi Yufang , Ning Guang , Zhou Libin , Wang Xiao 
Published: January 2019

AbstractProtein acetylation has a crucial role in energy metabolism. Here we performed the first large-scale profiling of acetylome in rat islets, showing that almost all enzymes in core metabolic pathways related to insulin secretion were acetylated. Label-free quantitative acetylome of islets in response to high glucose revealed hyperacetylation of enzymes involved in fatty acid β-oxidation (FAO), including trifunctional enzyme subunit alpha (ECHA). Acetylation decreased the protein stability of ECHA and its ability to promote FAO. The overexpression of SIRT3, a major mitochondrial deacetylase, prevented the degradation of ECHA via decreasing its acetylation level in β-cells. SIRT3 expression was upregulated in rat islets upon exposure to low glucose or fasting. SIRT3 overexpression in islets markedly decreased palmitate-potentiated insulin secretion, whereas islets from SIRT3 knockout mice secreted more insulin, with an opposite action on FAO. ECHA overexpression partially reversed SIRT3 deficiency-elicited insulin hypersecretion. Our study highlights the potential role of protein acetylation in insulin secretion.
CKIP-1 limits foam cell formation and inhibits atherosclerosis by promoting degradation of Oct-1 by REGγ
Authors: Fan Jiao , Liu Lifeng , Liu Qingyan , Cui Yu , Yao Binwei , Zhang Minghua , Gao Yabing , Fu Yesheng , Dai Hongmiao , Pan Jingkun , Qiu Ya , Liu Cui Hua , He Fuchu , Wang Yu , Zhang Lingqiang 
Published: January 2019

AbstractAtherosclerosis-related cardiovascular diseases are the leading cause of mortality worldwide. Macrophages uptake modified lipoproteins and transform into foam cells, triggering an inflammatory response and thereby promoting plaque formation. Here we show that casein kinase 2-interacting protein-1 (CKIP-1) is a suppressor of foam cell formation and atherosclerosis. Ckip-1 deficiency in mice leads to increased lipoprotein uptake and foam cell formation, indicating a protective role of CKIP-1 in this process. Ablation of Ckip-1 specifically upregulates the transcription of scavenger receptor LOX-1, but not that of CD36 and SR-A. Mechanistically, CKIP-1 interacts with the proteasome activator REGγ and targets the transcriptional factor Oct-1 for degradation, thereby suppressing the transcription of LOX-1 by Oct-1. Moreover, Ckip-1-deficient mice undergo accelerated atherosclerosis, and bone marrow transplantation reveals that Ckip-1 deficiency in hematopoietic cells is sufficient to increase atherosclerotic plaque formation. Therefore, CKIP-1 plays an essential anti-atherosclerotic role through regulation of foam cell formation and cholesterol metabolism.
FGL2 promotes tumor progression in the CNS by suppressing CD103+ dendritic cell differentiation
Authors: Yan Jun , Zhao Qingnan , Gabrusiewicz Konrad , Kong Ling-Yuan , Xia Xueqing , Wang Jian , Ott Martina , Xu Jingda , Davis R. Eric , Huo Longfei , Rao Ganesh , Sun Shao-Cong , Watowich Stephanie S. , Heimberger Amy B. , Li Shulin 
Published: January 2019

AbstractFew studies implicate immunoregulatory gene expression in tumor cells in arbitrating brain tumor progression. Here we show that fibrinogen-like protein 2 (FGL2) is highly expressed in glioma stem cells and primary glioblastoma (GBM) cells. FGL2 knockout in tumor cells did not affect tumor-cell proliferation in vitro or tumor progression in immunodeficient mice but completely impaired GBM progression in immune-competent mice. This impairment was reversed in mice with a defect in dendritic cells (DCs) or CD103+DC differentiation in the brain and in tumor-draining lymph nodes. The presence of FGL2 in tumor cells inhibited granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced CD103+DC differentiation by suppressing NF-κB, STAT1/5, and p38 activation. These findings are relevant to GBM patients because a low level ofFGL2expression with concurrent highGM-CSFexpression is associated with higherCD8Bexpression and longer survival. These data provide a rationale for therapeutic inhibition of FGL2 in brain tumors.
Rapidly receding Arctic Canada glaciers revealing landscapes continuously ice-covered for more than 40,000 years
Authors: Pendleton Simon L. , Miller Gifford H. , Lifton Nathaniel , Lehman Scott J. , Southon John , Crump Sarah E. , Anderson Robert S. 
Published: January 2019

AbstractArctic temperatures are increasing faster than the Northern Hemisphere average due to strong positive feedbacks unique to polar regions. However, the degree to which recent Arctic warming is unprecedented remains debated. Ages of entombed plants in growth position preserved by now receding ice caps in Arctic Canada help to address this issue by placing recent conditions in a multi-millennial context. Here we show that pre-Holocene radiocarbon dates on plants collected at the margins of 30 ice caps in Arctic Canada suggest those locations were continuously ice covered for > 40 kyr, but are now ice-free. We use in situ 14C inventories in rocks from nine locations to explore the possibility of brief exposure during the warm early Holocene. Modeling the evolution of in situ 14C confirms that Holocene exposure is unlikely at all but one of the sites. Viewed in the context of temperature records from Greenland ice cores, our results suggest that summer warmth of the past century exceeds now any century in ~115,000 years.
A highly active Ni(II)-triadamantylphosphine catalyst for ultrahigh-molecular-weight polyethylene synthesis
Authors: Kocen Andrew L. , Brookhart Maurice , Daugulis Olafs 
Published: January 2019

AbstractHere we report that the tri-1-adamantylphosphine-nickel complex [Ad3PNiBr3]-[Ad3PH]+ upon activation with an alkylaluminoxane catalyzes the polymerization of ethylene to ultrahigh-molecular-weight, nearly linear polyethylene (Mn up to 1.68 × 106 g mol−1) with initial activities reaching 3.7 million turnovers per h−1 at 10 °C. Copolymerizations of ethylene with α-olefins such as 1-hexene and 1-octadecene, as well as tert-butyldimethyl(dec-9-en-1-yloxy)silane give the corresponding copolymers with no decrease in activity.
Platinum-trimer decorated cobalt-palladium core-shell nanocatalyst with promising performance for oxygen reduction reaction
Authors: Dai Sheng , Chou Jyh-Pin , Wang Kuan-Wen , Hsu Yang-Yang , Hu Alice , Pan Xiaoqing , Chen Tsan-Yao 
Published: January 2019

AbstractAdvanced electrocatalysts with low platinum content, high activity and durability for the oxygen reduction reaction can benefit the widespread commercial use of fuel cell technology. Here, we report a platinum-trimer decorated cobalt-palladium core-shell nanocatalyst with a low platinum loading of only 2.4 wt% for the use in alkaline fuel cell cathodes. This ternary catalyst shows a mass activity that is enhanced by a factor of 30.6 relative to a commercial platinum catalyst, which is attributed to the unique charge localization induced by platinum-trimer decoration. The high stability of the decorated trimers endows the catalyst with an outstanding durability, maintaining decent electrocatalytic activity with no degradation for more than 322,000 potential cycles in alkaline electrolyte. These findings are expected to be useful for surface engineering and design of advanced fuel cell catalysts with atomic-scale platinum decoration.
Most Earth-surface calcites precipitate out of isotopic equilibrium
Authors: Daëron M. , Drysdale R. N. , Peral M. , Huyghe D. , Blamart D. , Coplen T. B. , Lartaud F. , Zanchetta G. 
Published: January 2019

AbstractOxygen-isotope thermometry played a critical role in the rise of modern geochemistry and remains extensively used in (bio-)geoscience. Its theoretical foundations rest on the assumption that 18O/16O partitioning among water and carbonate minerals primarily reflects thermodynamic equilibrium. However, after decades of research, there is no consensus on the true equilibrium 18O/16O fractionation between calcite and water (18αcc/w). Here, we constrain the equilibrium relations linking temperature, 18αcc/w, and clumped isotopes (Δ47) based on the composition of extremely slow-growing calcites from Devils Hole and Laghetto Basso (Corchia Cave). Equilibrium 18αcc/w values are systematically ~1.5‰ greater than those in biogenic and synthetic calcite traditionally considered to approach oxygen-isotope equilibrium. We further demonstrate that subtle disequilibria also affect Δ47 in biogenic calcite. These observations provide evidence that most Earth-surface calcites fail to achieve isotopic equilibrium, highlighting the need to improve our quantitative understanding of non-equilibrium isotope fractionation effects instead of relying on phenomenological calibrations.
Runx/Cbfβ complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation
Authors: Miyamoto Chizuko , Kojo Satoshi , Yamashita Motoi , Moro Kazuyo , Lacaud Georges , Shiroguchi Katsuyuki , Taniuchi Ichiro , Ebihara Takashi 
Published: January 2019

AbstractGroup 2 innate lymphoid cells (ILC2s) have tissue-resident competence and contribute to the pathogenesis of allergic diseases. However, the mechanisms regulating prolonged ILC2-mediated TH2 cytokine production under chronic inflammatory conditions are unclear. Here we show that, at homeostasis, Runx deficiency induces excessive ILC2 activation due to overly active GATA-3 functions. By contrast, during allergic inflammation, the absence of Runx impairs the ability of ILC2s to proliferate and produce effector TH2 cytokines and chemokines. Instead, functional deletion of Runx induces the expression of exhaustion markers, such as IL-10 and TIGIT, on ILC2s. Finally, these ‘exhausted-like’ ILC2s are unable to induce type 2 immune responses to repeated allergen exposures. Thus, Runx confers competence for sustained ILC2 activity at the mucosa, and contributes to allergic pathogenesis.
The evolution of human population distance to water in the USA from 1790 to 2010
Authors: Fang Yu , Jawitz James W. 
Published: January 2019

AbstractHuman societies evolved alongside rivers, but how has the relationship between human settlement locations and water resources evolved over time? We conducted a dynamic analysis in the conterminous US to assess the coevolution of humans and water resources from 1790 to 2010. Here we show that humans moved closer to major rivers in pre-industrial periods but have moved farther from major rivers after 1870, demonstrating the dynamics of human reliance on rivers for trade and transport. We show that humans were preferentially attracted to areas overlying major aquifers since industrialization due to the emergent accessibility of groundwater in the 20th century. Regional heterogeneity resulted in diverse trajectories of settlement proximity to major rivers, with the attractiveness of rivers increasing in arid regions and decreasing in humid areas. Our results reveal a historical coevolution of human-water systems, which could inform water management and contribute to societal adaptation to future climate change.
Ultra-high on-chip optical gain in erbium-based hybrid slot waveguides
Authors: Rönn John , Zhang Weiwei , Autere Anton , Leroux Xavier , Pakarinen Lasse , Alonso-Ramos Carlos , Säynätjoki Antti , Lipsanen Harri , Vivien Laurent , Cassan Eric , Sun Zhipei 
Published: January 2019

AbstractEfficient and reliable on-chip optical amplifiers and light sources would enable versatile integration of various active functionalities on the silicon platform. Although lasing on silicon has been demonstrated with semiconductors by using methods such as wafer bonding or molecular beam epitaxy, cost-effective mass production methods for CMOS-compatible active devices are still lacking. Here, we report ultra-high on-chip optical gain in erbium-based hybrid slot waveguides with a monolithic, CMOS-compatible and scalable atomic-layer deposition process. The unique layer-by-layer nature of atomic-layer deposition enables atomic scale engineering of the gain layer properties and straightforward integration with silicon integrated waveguides. We demonstrate up to 20.1 ± 7.31 dB/cm and at least 52.4 ± 13.8 dB/cm net modal and material gain per unit length, respectively, the highest performance achieved from erbium-based planar waveguides integrated on silicon. Our results show significant advances towards efficient on-chip amplification, opening a route to large-scale integration of various active functionalities on silicon.
The genome of broomcorn millet
Authors: Zou Changsong , Li Leiting , Miki Daisuke , Li Delin , Tang Qiming , Xiao Lihong , Rajput Santosh , Deng Ping , Peng Li , Jia Wei , Huang Ru , Zhang Meiling , Sun Yidan , Hu Jiamin , Fu Xing , Schnable Patrick S. , Chang Yuxiao , Li Feng , Zhang Hui , Feng Baili , Zhu Xinguang , Liu Renyi , Schnable James C. , Zhu Jian-Kang , Zhang Heng 
Published: January 2019

AbstractBroomcorn millet (Panicum miliaceum L.) is the most water-efficient cereal and one of the earliest domesticated plants. Here we report its high-quality, chromosome-scale genome assembly using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. Phylogenetic analyses reveal two sets of homologous chromosomes that may have merged ~5.6 million years ago, both of which exhibit strong synteny with other grass species. Broomcorn millet contains 55,930 protein-coding genes and 339 microRNA genes. We find Paniceae-specific expansion in several subfamilies of the BTB (broad complex/tramtrack/bric-a-brac) subunit of ubiquitin E3 ligases, suggesting enhanced regulation of protein dynamics may have contributed to the evolution of broomcorn millet. In addition, we identify the coexistence of all three C4 subtypes of carbon fixation candidate genes. The genome sequence is a valuable resource for breeders and will provide the foundation for studying the exceptional stress tolerance as well as C4 biology.
A programmable two-qubit solid-state quantum processor under ambient conditions
Authors: Wu Yang , Wang Ya , Qin Xi , Rong Xing , Du Jiangfeng 
Published: January 2019

AbstractQuantum computers, which take advantage of the superposition and entanglement of physical states, could outperform their classical counterparts in solving problems with technological impact such as factoring large numbers and searching databases. A quantum processor executes algorithms by applying a programmable sequence of gates to an initialized state of qubits, which coherently evolves into a final state containing the result of the computation. Although quantum processors with a few qubits have been demonstrated on multiple quantum computing platforms, realization of solid-state programmable quantum processor under ambient conditions remains elusive. Here we report a programable quantum processor that can be programmed with fifteen parameters to realize arbitrary unitary transformations on two spin qubits in a nitrogen-vacancy (NV) center in diamond. We implemented the Deutsch-Jozsa and Grover search algorithms with average success rates above 80%. The results pave the way to implement the programmable method in a large-scale quantum processor.
Establishment and Validation of Extra-transitional Zone Prostate Specific Antigen Density (ETzD), a Novel Structure-based Parameter for Quantifying the Oncological Hazard of Prostates with Enlarged Stroma
Authors: Kim Jung Jun , Suh Yoon Seok , Kim Tae Heon , Jeon Seong Soo , Lee Hyun Moo , Choi Han Yong , Kim Seonwoo , Lee Kyu-Sung 
Published: January 2019

AbstractExtra-transitional zone density (ETzD), a novel parameter is proposed to stratify the deviation of prostate specific antigen (PSA) due to structural change according to stromal hyperplasia of prostate. ETzD was conducted on a concept to estimate the PSA density (PSAD) after hypothetical enucleation of the transitional zone of an enlarged prostate by a non-linear regression prediction model with intrinsic linearity, from the retrospective analysis of PSA change observed actual enucleation by laser. The performance to predict the presence and severity of malignancy was validated by two cohorts of 3,440 prostate biopsies and 2,783 radical prostatectomy specimens. The performance of ETzD was compared with conventional parameters. The receiver operative curve of area under curve (AUC) of ETzD to predict the presence of malignacy was 0.862 (95% CI; 0.843~0.881), better than PSA, PSAD or transitional zone PSAD (TzPSAD). The AUC of ETzD to predict an unfavorable cancer among prostate cancer patients was 0.736 (95% CI; 0.705~0.768), which performs better than PSA and comparable to PSAD or TzPSAD. In summary, the performance of ETzD as a universal parameter to quantify the oncological hazard of a prostate was validated and the superiority to conventional parameters was verified.
Low energy expenditure and resting behaviour of humpback whale mother-calf pairs highlights conservation importance of sheltered breeding areas
Authors: Bejder L. , Videsen S. , Hermannsen L. , Simon M. , Hanf D. , Madsen P. T. 
Published: January 2019

AbstractUnderstanding the behaviour of humpback whale mother-calf pairs and the acoustic environment on their breeding grounds is fundamental to assessing the biological and ecological requirements needed to ensure a successful migration and survival of calves. Therefore, on a breeding/resting ground, Exmouth Gulf, Western Australia, we used animal-borne DTAGs to quantify the fine-scale behaviour and energetic expenditure of humpback whale mothers and calves, while sound recorders measured the acoustic environment. We show that: (i) lactating humpback whales keep their energy expenditure low by devoting a significant amount of time to rest, and their use of energy, inferred from respiration rates, is ~half than that of adults on their foraging grounds; (ii) lactating females mainly rest while stationary at shallow depths within reach of the hull of commercial ships, thus increasing the potential for ship strike collisions; (iii) the soundscape is dominated by biological sources; and (iv) even moderate increases of noise from vessels will decrease the communication range of humpback whales. Planned commercial infrastructure in Exmouth Gulf will cause a substantial increase in shipping traffic with the risk of ship strikes and acoustic disturbance potentially compromising energy reserves for the southern migration of humpback whales.