bluuebunny/crossref_metadata_2025_split huggingface dataset:
c-Jun-mediated microRNA-302d-3p induces RPE dedifferentiation by targeting p21Waf1/Cip1
Authors: Jiang Chao , Xie Ping , Sun Ruxu , Sun Xiantao , Liu Guohua , Ding Sijia , Zhu Meidong , Yan Biao , Liu Qinghuai , Chen Xue , Zhao Chen 
Published: April 2018

AbstractDedifferentiation of retinal pigment epithelium (RPE) cells and choroidal neovascularization (CNV) contributes to the pathogenesis of age-related macular degeneration (AMD). MicroRNAs (miRNAs) have crucial roles in AMD onset and progression. We thus aim to investigate the effects of miRNAs on RPE dedifferentiation and endothelium cell (EC) behavior, and analyze its downstream pathways. We have previously identified miR-302d-3p as the most downregulated miRNA signature along with RPE differentiation. Herein, in vitro study supported that miR-302d-3p induces RPE dedifferentiation typified by reduction of RPE characteristic markers, interrupts its phagocytosis, and promotes its migration, proliferation, and cell-cycle progression. c-Jun was identified as a potential upstream transcript factor for MIR302D, which might modulate RPE function by regulating miR-302d-3p expression. P21Waf1/Cip1, a cyclin-dependent kinase inhibitor encoded by the CDKN1A gene, was identified as a downstream target of miR-302d-3p. Our data suggested that p21Waf1/Cip1 could promote RPE differentiation, and inhibit its proliferation, migration, and cell-cycle progression. We also demonstrated that miR-302d-3p suppresses RPE differentiation through directly targeting p21Waf1/Cip1. In addition, the miR-302d-3p/CDKN1A axis was also involved in regulating tube formation of ECs, indicating its potential involvement in CNV formation. Taken together, our study implies that miR-302d-3p, regulated by c-Jun, contributes to the pathogenesis of both atrophic and exudative AMD. MiR-302d-3p promotes RPE dedifferentiation, migration, proliferation and cell-cycle progression, inhibits RPE phagocytosis, and induces abnormal EC behavior by targeting p21Waf1/Cip1. Pharmacological miR-302d-3p inhibitors are prospective therapeutic options for prevention and treatment of AMD.
Starvation during pregnancy impairs fetal oogenesis and folliculogenesis in offspring in the mouse
Authors: Wang Jun-Jie , Yu Xiao-Wei , Wu Rui-Ying , Sun Xiao-Feng , Cheng Shun-Feng , Ge Wei , Liu Jing-Cai , Li Ya-Peng , Liu Jing , Zou Shu-Hua , De Felici Massimo , Shen Wei 
Published: April 2018

AbstractAlthough it is becoming increasingly evident that maternal starvation during pregnancy can have permanent effects on a range of physiological processes in the offspring, scant information is available about the consequence of such condition for oogenesis and hence for lifetime reproductive success of progeny in mammals. In the present study, we address this topic by starving pregnant mice at the time of ovarian differentiation (12.5 days post coitum (dpc)) for three consecutive days and analyzed the consequence first on the survival of the fetal oocytes and their capability to progress throughout the stages of meiotic prophase I (MPI) and then on the postnatal folliculogenesis of the offspring. The results showed that maternal starvation increased apoptosis in the fetal ovaries, resulting in reduction of the oocyte number. Moreover, MPI progression was slowed down in the surviving oocytes and the expression of DNA repair players in the starved ovaries increased. Transcriptome analysis identified 61 differentially expressed genes between control and starved ovaries, the most part of these being involved in metabolic processes. A significant decrease in the percentage of oocytes enclosed in primordial follicles and the expression of oocyte genes critically involved in folliculogenesis such as Nobox, Lhx8 and Sohlh2 in the 3 days post partum (dpp) starved ovaries were found. Finally, at the time of juvenile period (21 dpp), the number of oocytes and antral follicles resulted significantly lower in the ovaries of the offspring from starved mothers in comparison to controls. Our findings support the notion that maternal starvation can affect ovary development in the offspring that could adversely affect their reproductive success in the adult life.
Zika virus propagation and release in human fetal astrocytes can be suppressed by neutral sphingomyelinase-2 inhibitor GW4869
Authors: Huang Yunlong , Li Yuju , Zhang Hainan , Zhao Runze , Jing Ran , Xu Yinghua , He Miao , Peer Justin , Kim Yeong C. , Luo Jiangtao , Tong Zenghan , Zheng Jialin 
Published: April 2018

AbstractZika virus (ZIKV) is a neurotrophic flavivirus that is capable of infecting humans, leading to brain abnormalities during fetal development. The ZIKV infectivity in neural target cells remains poorly understood. Here, we found that ZIKV specifically infected glial fibrillary acidic protein- and S100B-positive primary human astrocytes derived from fetal brains. In contrast, neuron-specific Class III β-tubulin (TuJ1)-positive neurons in the astrocyte cultures and SOX2-positive neural progenitor cells derived from the fetal brains were less susceptible to ZIKV infection compared with astrocytes. The infected astrocytes released competent viral particles and manifested programmed cell death with a progressive cytopathic effect. Interestingly, ZIKV infection in human fetal astrocytes induced a significant increase of extracellular vesicles (EVs). Treatment with GW4869, a specific inhibitor of neutral sphingomyelinase-2, decreased EV levels, suppressed ZIKV propagation, and reduced the release of infectious virions in astrocytes. Therefore, ZIKV infects primary human fetal astrocytes and the infection can be suppressed by neutral sphingomyelinase-2 inhibitor GW4869. Further investigation into sphingomyelin metabolism and EVs may provide insights to the therapeutic treatment of ZIKV infection.
Deep whole-genome sequencing reveals recent selection signatures linked to evolution and disease risk of Japanese
Authors: Okada Yukinori , Momozawa Yukihide , Sakaue Saori , Kanai Masahiro , Ishigaki Kazuyoshi , Akiyama Masato , Kishikawa Toshihiro , Arai Yasumichi , Sasaki Takashi , Kosaki Kenjiro , Suematsu Makoto , Matsuda Koichi , Yamamoto Kazuhiko , Kubo Michiaki , Hirose Nobuyoshi , Kamatani Yoichiro 
Published: April 2018

AbstractUnderstanding natural selection is crucial to unveiling evolution of modern humans. Here, we report natural selection signatures in the Japanese population using 2234 high-depth whole-genome sequence (WGS) data (25.9×). Using rare singletons, we identify signals of very recent selection for the past 2000–3000 years in multiple loci (ADH cluster, MHC region,BRAP-ALDH2,SERHL2). In large-scale genome-wide association study (GWAS) dataset (n = 171,176), variants with selection signatures show enrichment in heterogeneity of derived allele frequency spectra among the geographic regions of Japan, highlighted by two major regional clusters (Hondo and Ryukyu). While the selection signatures do not show enrichment in archaic hominin-derived genome sequences, they overlap with the SNPs associated with the modern human traits. The strongest overlaps are observed for the alcohol or nutrition metabolism-related traits. Our study illustrates the value of high-depth WGS to understand evolution and their relationship with disease risk.
The Gastrodia elata genome provides insights into plant adaptation to heterotrophy
Authors: Yuan Yuan , Jin Xiaohua , Liu Juan , Zhao Xing , Zhou Junhui , Wang Xin , Wang Deyi , Lai Changjiangsheng , Xu Wei , Huang Jingwen , Zha Liangping , Liu Dahui , Ma Xiao , Wang Li , Zhou Menyan , Jiang Zhi , Meng Hubiao , Peng Huasheng , Liang Yuting , Li Ruiqiang , Jiang Chao , Zhao Yuyang , Nan Tiegui , Jin Yan , Zhan Zhilai , Yang Jian , Jiang Wenkai , Huang Luqi 
Published: April 2018

AbstractWe present the 1.06 Gb sequenced genome of Gastrodia elata, an obligate mycoheterotrophic plant, which contains 18,969 protein-coding genes. Many genes conserved in other plant species have been deleted from the G. elata genome, including most of those for photosynthesis. Additional evidence of the influence of genome plasticity in the adaptation of this mycoheterotrophic lifestyle is evident in the large number of gene families that are expanded in G. elata, including glycoside hydrolases and urease that likely facilitate the digestion of hyphae are expanded, as are genes associated with strigolactone signaling, and ATPases that may contribute to the atypical energy metabolism. We also find that the plastid genome of G. elata is markedly smaller than that of green plant species while its mitochondrial genome is one of the largest observed to date. Our report establishes a foundation for studying adaptation to a mycoheterotrophic lifestyle.
Precisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing
Authors: Kim Soon Hee , Yeon Yeung Kyu , Lee Jung Min , Chao Janet Ren , Lee Young Jin , Seo Ye Been , Sultan Md. Tipu , Lee Ok Joo , Lee Ji Seung , Yoon Sung-il , Hong In-Sun , Khang Gilson , Lee Sang Jin , Yoo James J. , Park Chan Hum 
Published: April 2018

AbstractAlthough three-dimensional (3D) bioprinting technology has gained much attention in the field of tissue engineering, there are still several significant engineering challenges to overcome, including lack of bioink with biocompatibility and printability. Here, we show a bioink created from silk fibroin (SF) for digital light processing (DLP) 3D bioprinting in tissue engineering applications. The SF-based bioink (Sil-MA) was produced by a methacrylation process using glycidyl methacrylate (GMA) during the fabrication of SF solution. The mechanical and rheological properties of Sil-MA hydrogel proved to be outstanding in experimental testing and can be modulated by varying the Sil-MA contents. This Sil-MA bioink allowed us to build highly complex organ structures, including the heart, vessel, brain, trachea and ear with excellent structural stability and reliable biocompatibility. Sil-MA bioink is well-suited for use in DLP printing process and could be applied to tissue and organ engineering depending on the specific biological requirements.
The basic helix-loop-helix transcription factor SHARP1 is an oncogenic driver in MLL-AF6 acute myelogenous leukemia
Authors: Numata Akihiko , Kwok Hui Si , Kawasaki Akira , Li Jia , Zhou Qi-Ling , Kerry Jon , Benoukraf Touati , Bararia Deepak , Li Feng , Ballabio Erica , Tapia Marta , Deshpande Aniruddha J. , Welner Robert S. , Delwel Ruud , Yang Henry , Milne Thomas A. , Taneja Reshma , Tenen Daniel G. 
Published: April 2018

AbstractAcute Myeloid Leukemia (AML) with MLL gene rearrangements demonstrate unique gene expression profiles driven by MLL-fusion proteins. Here, we identify the circadian clock transcription factor SHARP1 as a novel oncogenic target in MLL-AF6 AML, which has the worst prognosis among all subtypes of MLL-rearranged AMLs. SHARP1 is expressed solely in MLL-AF6 AML, and its expression is regulated directly by MLL-AF6/DOT1L. Suppression of SHARP1 induces robust apoptosis of human MLL-AF6 AML cells. Genetic deletion in mice delays the development of leukemia and attenuated leukemia-initiating potential, while sparing normal hematopoiesis. Mechanistically, SHARP1 binds to transcriptionally active chromatin across the genome and activates genes critical for cell survival as well as key oncogenic targets of MLL-AF6. Our findings demonstrate the unique oncogenic role for SHARP1 in MLL-AF6 AML.
Dissociation of two-dimensional excitons in monolayer WSe2
Authors: Massicotte Mathieu , Vialla Fabien , Schmidt Peter , Lundeberg Mark B. , Latini Simone , Haastrup Sten , Danovich Mark , Davydovskaya Diana , Watanabe Kenji , Taniguchi Takashi , Fal’ko Vladimir I. , Thygesen Kristian S. , Pedersen Thomas G. , Koppens Frank H. L. 
Published: April 2018

AbstractTwo-dimensional (2D) semiconducting materials are promising building blocks for optoelectronic applications, many of which require efficient dissociation of excitons into free electrons and holes. However, the strongly bound excitons arising from the enhanced Coulomb interaction in these monolayers suppresses the creation of free carriers. Here, we identify the main exciton dissociation mechanism through time and spectrally resolved photocurrent measurements in a monolayer WSe2p–n junction. We find that under static in-plane electric field, excitons dissociate at a rate corresponding to the one predicted for tunnel ionization of 2D Wannier–Mott excitons. This study is essential for understanding the photoresponse of 2D semiconductors and offers design rules for the realization of efficient photodetectors, valley dependent optoelectronics, and novel quantum coherent phases.
Universality in volume-law entanglement of scrambled pure quantum states
Authors: Nakagawa Yuya O. , Watanabe Masataka , Fujita Hiroyuki , Sugiura Sho 
Published: April 2018

AbstractA pure quantum state can fully describe thermal equilibrium as long as one focuses on local observables. The thermodynamic entropy can also be recovered as the entanglement entropy of small subsystems. When the size of the subsystem increases, however, quantum correlations break the correspondence and mandate a correction to this simple volume law. The elucidation of the size dependence of the entanglement entropy is thus essentially important in linking quantum physics with thermodynamics. Here we derive an analytic formula of the entanglement entropy for a class of pure states called cTPQ states representing equilibrium. We numerically find that our formula applies universally to any sufficiently scrambled pure state representing thermal equilibrium, i.e., energy eigenstates of non-integrable models and states after quantum quenches. Our formula is exploited as diagnostics for chaotic systems; it can distinguish integrable models from non-integrable models and many-body localization phases from chaotic phases.
Capping protein-controlled actin polymerization shapes lipid membranes
Authors: Dürre Katharina , Keber Felix C. , Bleicher Philip , Brauns Fridtjof , Cyron Christian J. , Faix Jan , Bausch Andreas R. 
Published: April 2018

AbstractArp2/3 complex-mediated actin assembly at cell membranes drives the formation of protrusions or endocytic vesicles. To identify the mechanism by which different membrane deformations can be achieved, we reconstitute the basic membrane deformation modes of inward and outward bending in a confined geometry by encapsulating a minimal set of cytoskeletal proteins into giant unilamellar vesicles. Formation of membrane protrusions is favoured at low capping protein (CP) concentrations, whereas the formation of negatively bent domains is promoted at high CP concentrations. Addition of non-muscle myosin II results in full fission events in the vesicle system. The different deformation modes are rationalized by simulations of the underlying transient nature of the reaction kinetics. The relevance of the regulatory mechanism is supported by CP overexpression in mouse melanoma B16-F1 cells and therefore demonstrates the importance of the quantitative understanding of microscopic kinetic balances to address the diverse functionality of the cytoskeleton.
Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers
Authors: Lanjakornsiripan Darin , Pior Baek-Jun , Kawaguchi Daichi , Furutachi Shohei , Tahara Tomoaki , Katsuyama Yu , Suzuki Yutaka , Fukazawa Yugo , Gotoh Yukiko 
Published: April 2018

AbstractNon-pial neocortical astrocytes have historically been thought to comprise largely a nondiverse population of protoplasmic astrocytes. Here we show that astrocytes of the mouse somatosensory cortex manifest layer-specific morphological and molecular differences. Two- and three-dimensional observations revealed that astrocytes in the different layers possess distinct morphologies as reflected by differences in cell orientation, territorial volume, and arborization. The extent of ensheathment of synaptic clefts by astrocytes in layer II/III was greater than that by those in layer VI. Moreover, differences in gene expression were observed between upper-layer and deep-layer astrocytes. Importantly, layer-specific differences in astrocyte properties were abrogated inreelerandDab1conditional knockout mice, in which neuronal layers are disturbed, suggesting that neuronal layers are a prerequisite for the observed morphological and molecular differences of neocortical astrocytes. This study thus demonstrates the existence of layer-specific interactions between neurons and astrocytes, which may underlie their layer-specific functions.
Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4DCAF5 ubiquitin ligase
Authors: Leng Feng , Yu Jiekai , Zhang Chunxiao , Alejo Salvador , Hoang Nam , Sun Hong , Lu Fei , Zhang Hui 
Published: April 2018

AbstractMany non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4DCAF5. Mouse L3MBTL3/MBT-1 deletion causes accumulation of DNMT1 protein, increased genomic DNA methylation, and late embryonic lethality. DNMT1 contains a consensus methylation motif shared by many non-histone proteins including E2F1, a key transcription factor for S phase. We show that the methylation-dependent E2F1 degradation is also controlled by L3MBTL3-CRL4DCAF5. Our studies elucidate for the first time a novel mechanism by which the stability of many methylated non-histone proteins are regulated.
Molecular doping enabled scalable blading of efficient hole-transport-layer-free perovskite solar cells
Authors: Wu Wu-Qiang , Wang Qi , Fang Yanjun , Shao Yuchuan , Tang Shi , Deng Yehao , Lu Haidong , Liu Ye , Li Tao , Yang Zhibin , Gruverman Alexei , Huang Jinsong 
Published: April 2018

AbstractThe efficiencies of perovskite solar cells (PSCs) are now reaching such consistently high levels that scalable manufacturing at low cost is becoming critical. However, this remains challenging due to the expensive hole-transporting materials usually employed, and difficulties associated with the scalable deposition of other functional layers. By simplifying the device architecture, hole-transport-layer-free PSCs with improved photovoltaic performance are fabricated via a scalable doctor-blading process. Molecular doping of halide perovskite films improved the conductivity of the films and their electronic contact with the conductive substrate, resulting in a reduced series resistance. It facilitates the extraction of photoexcited holes from perovskite directly to the conductive substrate. The bladed hole-transport-layer-free PSCs showed a stabilized power conversion efficiency above 20.0%. This work represents a significant step towards the scalable, cost-effective manufacturing of PSCs with both high performance and simple fabrication processes.
Bio-inspired nano-traps for uranium extraction from seawater and recovery from nuclear waste
Authors: Sun Qi , Aguila Briana , Perman Jason , Ivanov Aleksandr S. , Bryantsev Vyacheslav S. , Earl Lyndsey D. , Abney Carter W. , Wojtas Lukasz , Ma Shengqian 
Published: April 2018

AbstractNature can efficiently recognize specific ions by exerting second-sphere interactions onto well-folded protein scaffolds. However, a considerable challenge remains to artificially manipulate such affinity, while being cost-effective in managing immense amounts of water samples. Here, we propose an effective approach to regulate uranyl capture performance by creating bio-inspired nano-traps, illustrated by constructing chelating moieties into porous frameworks, where the binding motif’s coordinative interaction towards uranyl is enhanced by introducing an assistant group, reminiscent of biological systems. Representatively, the porous framework bearing 2-aminobenzamidoxime is exceptional in sequestering high uranium concentrations with sufficient capacities (530 mg g−1) and trace quantities, including uranium in real seawater (4.36 mg g−1, triple the benchmark). Using a combination of spectroscopic, crystallographic, and theory calculation studies, it is revealed that the amino substituent assists in lowering the charge on uranyl in the complex and serves as a hydrogen bond acceptor, boosting the overall uranyl affinity of amidoxime.
De novo main-chain modeling for EM maps using MAINMAST
Authors: Terashi Genki , Kihara Daisuke 
Published: April 2018

AbstractAn increasing number of protein structures are determined by cryo-electron microscopy (cryo-EM) at near atomic resolution. However, tracing the main-chains and building full-atom models from EM maps of ~4–5 Å is still not trivial and remains a time-consuming task. Here, we introduce a fully automated de novo structure modeling method, MAINMAST, which builds three-dimensional models of a protein from a near-atomic resolution EM map. The method directly traces the protein’s main-chain and identifies Cα positions as tree-graph structures in the EM map. MAINMAST performs significantly better than existing software in building global protein structure models on data sets of 40 simulated density maps at 5 Å resolution and 30 experimentally determined maps at 2.6–4.8 Å resolution. In another benchmark of building missing fragments in protein models for EM maps, MAINMAST builds fragments of 11–161 residues long with an average RMSD of 2.68 Å.
Galectin-3 deficiency drives lupus-like disease by promoting spontaneous germinal centers formation via IFN-γ
Authors: Beccaria Cristian Gabriel , Amezcua Vesely María Carolina , Fiocca Vernengo Facundo , Gehrau Ricardo Carlos , Ramello María Cecilia , Tosello Boari Jimena , Gorosito Serrán Melisa , Mucci Juan , Piaggio Eliane , Campetella Oscar , Acosta Rodríguez Eva Virginia , Montes Carolina Lucía , Gruppi Adriana 
Published: April 2018

AbstractGerminal centers (GC) are important sites for high-affinity and long-lived antibody induction. Tight regulation of GC responses is critical for maintaining self-tolerance. Here, we show that Galectin-3 (Gal-3) is involved in GC development. Compared with WT mice, Gal-3 KO mice have more GC B cells and T follicular helper cells, increased percentages of antibody-secreting cells and higher concentrations of immunoglobulins and IFN-γ in serum, and develop a lupus-like disease. IFN-γ blockade in Gal-3 KO mice reduces spontaneous GC formation, class-switch recombination, autoantibody production and renal pathology, demonstrating that IFN-γ overproduction sustains autoimmunity. The results from chimeric mice show that intrinsic Gal-3 signaling in B cells controls spontaneous GC formation. Taken together, our data provide evidence that Gal-3 acts directly on B cells to regulate GC responses via IFN-γ and implicate the potential of Gal-3 as a therapeutic target in autoimmunity.