bluuebunny/crossref_metadata_2025_split huggingface dataset:
ESCRT-III is necessary for the integrity of the nuclear envelope in micronuclei but is aberrant at ruptured micronuclear envelopes generating damage
Authors: Willan Jessica , Cleasby Alexa J. , Flores-Rodriguez Neftali , Stefani Flavia , Rinaldo Cinzia , Pisciottani Alessandra , Grant Emma , Woodman Philip , Bryant Helen E. , Ciani Barbara 
Published: April 2019

AbstractMicronuclei represent the cellular attempt to compartmentalize DNA to maintain genomic integrity threatened by mitotic errors and genotoxic events. Some micronuclei show aberrant nuclear envelopes (NEs) that collapse, generating damaged DNA that can promote complex genome alterations. However, ruptured micronuclei also provide a pool of cytosolic DNA that can stimulate antitumor immunity, revealing the complexity of micronuclear impact on tumor progression. The ESCRT-III (Endosomal Sorting Complex Required for Transport-III) complex ensures NE reseals during late mitosis and is repaired in interphase. Therefore, ESCRT-III activity maybe crucial for maintaining the integrity of other genomic structures enclosed by a NE. ESCRT-III activity at the NE is coordinated by the subunit CHMP7. We show that CHMP7 and ESCRT-III protect against the genomic instability associated with micronuclei formation. Loss of ESCRT-III activity increases the population of micronuclei with ruptured NEs, revealing that its NE repair activity is also necessary to maintain micronuclei integrity. Surprisingly, aberrant accumulation of ESCRT-III are found at the envelope of most acentric collapsed micronuclei, suggesting that ESCRT-III is not recycled efficiently from these structures. Moreover, CHMP7 depletion relieves micronuclei from the aberrant accumulations of ESCRT-III. CHMP7-depleted cells display a reduction in micronuclei containing the DNA damage marker RPA and a sensor of cytosolic DNA. Thus, ESCRT-III activity appears to protect from the consequence of genomic instability in a dichotomous fashion: ESCRT-III membrane repair activity prevents the occurrence of micronuclei with weak envelopes, but the aberrant accumulation of ESCRT-III on a subset of micronuclei appears to exacerbate DNA damage and sustain proinflammatory pathways.
MicroRNA-196a/-196b regulate the progression of hepatocellular carcinoma through modulating the JAK/STAT pathway via targeting SOCS2
Authors: Ren Weihua , Wu Shuangting , Wu Yabin , Liu Tan , Zhao Xingpeng , Li Yawei 
Published: April 2019

AbstractmicroRNAs (miRNAs) play essential roles in progression of hepatocellular carcinoma (HCC). However, the roles of miR-196a and miR-196b as well as mechanism in HCC progression remain poorly understood. The expressions of miR-196a, miR-196b and suppressor of cytokine signaling 2 (SOCS2) were measured in HCC tissues and cells by quantitative real-time polymerase chain reaction or immunohistochemistry. HCC progression was investigated by cell proliferation, glycolysis, cycle, clones, apoptosis, and necrosis. The interaction between SOCS2 and miR-196a or miR-196b was explored by luciferase activity and RNA immunoprecipitation analyses. The expressions of proteins in Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway were measured by western blot. A xenograft model was established to investigate the roles of miR-196a or miR-196b in vivo. We found that miR-196a and miR-196b were highly expressed in HCC tissues and cells. High expression of miR-196a or miR-196b was correlated with tumor size, tumor-node-metastasis stage, lymph node metastasis, albumin–bilirubin grade and poor 5-year survival. Knockdown of miR-196a or miR-196b suppressed cell proliferation, glycolysis, cell cycle process, colony formation but induced apoptosis or necrosis in HCC cells. SOCS2 was targeted by miR-196a and miR-196b and its interference ablated abrogation of miR-196a or miR-196b-mediated inhibitory effect on HCC progression. SOCS2 was negatively associated with activation of the JAK/STAT pathway. Besides, knockdown of miR-196a or miR-196b limited xenograft tumor growth by blocking the JAK/STAT pathway. We concluded that downregulation of miR-196a or miR-196b inhibited HCC progression through regulating the JAK/STAT pathway via targeting SOCS2, providing novel targets for prognosis and therapeutics of HCC.
Ferritinophagy is required for the induction of ferroptosis by the bromodomain protein BRD4 inhibitor (+)-JQ1 in cancer cells
Authors: Sui Shiyao , Zhang Jian , Xu Shouping , Wang Qin , Wang Peiyuan , Pang Da 
Published: April 2019

Abstract(+)-JQ1 is an inhibitor of the tumor-driver bromodomain protein BRD4 and produces satisfactory effects because it efficiently increases apoptosis. Ferroptosis is an oxidative cell death program differing from apoptosis. Ferroptosis is characterized by high levels of iron and reactive oxygen species and has been confirmed to suppress tumor growth. In this study, BRD4 expression in cancer and its influence on the prognosis of cancer patients were analyzed using data from public databases. In addition, the effect of the BRD4 inhibitor (+)-JQ1 on ferroptosis was investigated via a series of in vitro assays. A nude mouse model was used to evaluate the function of (+)-JQ1 in ferroptosis in vivo. The potential mechanisms by which (+)-JQ1 regulates ferroptosis were explored. The results showed that BRD4 expression levels were higher in cancer tissues than in normal tissues and were related to poor prognosis in cancer patients. Furthermore, ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition. Moreover, the anticancer effect of (+)-JQ1 was enhanced by ferroptosis inducers. Further studies confirmed that (+)-JQ1 induced ferroptosis via ferritinophagy, which featured autophagy enhancement by (+)-JQ1 and increased iron levels. Subsequently, the reactive oxygen species levels were increased by iron via the Fenton reaction, leading to ferroptosis. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 may regulate ferroptosis by controlling the expression of ferroptosis-associated genes regulated by BRD4. Finally, (+)-JQ1 regulated ferritinophagy and the expression of ferroptosis-associated genes via epigenetic inhibition of BRD4 by suppressing the expression of the histone methyltransferase G9a or enhancing the expression of the histone deacetylase SIRT1. In summary, the BRD4 inhibitor (+)-JQ1 induces ferroptosis via ferritinophagy or the regulation of ferroptosis-associated genes through epigenetic repression of BRD4.
Light chain modulates heavy chain conformation to change protection profile of monoclonal antibodies against influenza A viruses
Authors: Xiao Haixia , Guo Tianling , Yang Mi , Qi Jianxun , Huang Chaobin , Hong Yuanyuan , Gu Jinjin , Pang Xuefei , Liu William Jun , Peng Ruchao , McCauley John , Bi Yuhai , Li Shihua , Feng Junxia , Zhang Hailiang , Zhang Xupei , Lu Xishan , Yan Jinghua , Chen Liling , Shi Yi , Chen Weizhi , Gao George Fu 
Published: April 2019

AbstractThe isolation of human monoclonal antibodies with broadly neutralizing breadth can provide a promising countermeasure for influenza A viruses infection. Most broadly neutralizing antibodies against influenza A viruses bind to the conserved stem region or the receptor-binding cavity of hemagglutinin and the interaction is dominated by the heavy chain. The light chain, however, contributes few or no direct contacts to the antigen. Here we report an H3-clade neutralizing human monoclonal antibody, AF4H1K1, which recognizes the hemagglutinin glycoproteins of all group 2 influenza A viruses. This human monoclonal antibody has been obtained through the screening by pairing different heavy and light chains from an H7N9-infected patient based on the next-generation sequencing technology. Further structural studies revealed that light chains modulate the neutralizing spectrum by affecting the local conformation of heavy chains, instead of direct interaction with the antigen. These findings provide important clues to understand the molecular basis of light chains in antigen recognition and to explore the strategies in particular of the use of light chain modification to develop broadly protective monoclonal antibodies against influenza A viruses and other emerging viruses.
Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors
Authors: Lux Michaelyn C. , Standke Lisa C. , Tan Derek S. 
Published: April 2019

AbstractAdenylate-forming enzymes are a mechanistic superfamily that are involved in diverse biochemical pathways. They catalyze ATP-dependent activation of carboxylic acid substrates as reactive acyl adenylate (acyl-AMP) intermediates and subsequent coupling to various nucleophiles to generate ester, thioester, and amide products. Inspired by natural products, acyl sulfonyladenosines (acyl-AMS) that mimic the tightly bound acyl-AMP reaction intermediates have been developed as potent inhibitors of adenylate-forming enzymes. This simple yet powerful inhibitor design platform has provided a wide range of biological probes as well as several therapeutic lead compounds. Herein, we provide an overview of the nine structural classes of adenylate-forming enzymes and examples of acyl-AMS inhibitors that have been developed for each.
Accelerating dynamics of collective attention
Authors: Lorenz-Spreen Philipp , Mønsted Bjarke Mørch , Hövel Philipp , Lehmann Sune 
Published: April 2019

AbstractWith news pushed to smart phones in real time and social media reactions spreading across the globe in seconds, the public discussion can appear accelerated and temporally fragmented. In longitudinal datasets across various domains, covering multiple decades, we find increasing gradients and shortened periods in the trajectories of how cultural items receive collective attention. Is this the inevitable conclusion of the way information is disseminated and consumed? Our findings support this hypothesis. Using a simple mathematical model of topics competing for finite collective attention, we are able to explain the empirical data remarkably well. Our modeling suggests that the accelerating ups and downs of popular content are driven by increasing production and consumption of content, resulting in a more rapid exhaustion of limited attention resources. In the interplay with competition for novelty, this causes growing turnover rates and individual topics receiving shorter intervals of collective attention.
Supersonic plasma turbulence in the laboratory
Authors: White T. G. , Oliver M. T. , Mabey P. , Kühn-Kauffeldt M. , Bott A. F. A. , Döhl L. N. K. , Bell A. R. , Bingham R. , Clarke R. , Foster J. , Giacinti G. , Graham P. , Heathcote R. , Koenig M. , Kuramitsu Y. , Lamb D. Q. , Meinecke J. , Michel Th. , Miniati F. , Notley M. , Reville B. , Ryu D. , Sarkar S. , Sakawa Y. , Selwood M. P. , Squire J. , Scott R. H. H. , Tzeferacos P. , Woolsey N. , Schekochihin A. A. , Gregori G. 
Published: April 2019

AbstractThe properties of supersonic, compressible plasma turbulence determine the behavior of many terrestrial and astrophysical systems. In the interstellar medium and molecular clouds, compressible turbulence plays a vital role in star formation and the evolution of our galaxy. Observations of the density and velocity power spectra in the Orion B and Perseus molecular clouds show large deviations from those predicted for incompressible turbulence. Hydrodynamic simulations attribute this to the high Mach number in the interstellar medium (ISM), although the exact details of this dependence are not well understood. Here we investigate experimentally the statistical behavior of boundary-free supersonic turbulence created by the collision of two laser-driven high-velocity turbulent plasma jets. The Mach number dependence of the slopes of the density and velocity power spectra agree with astrophysical observations, and supports the notion that the turbulence transitions from being Kolmogorov-like at low Mach number to being more Burgers-like at higher Mach numbers.
Engineering Auger recombination in colloidal quantum dots via dielectric screening
Authors: Hou Xiaoqi , Kang Jun , Qin Haiyan , Chen Xuewen , Ma Junliang , Zhou Jianhai , Chen Liping , Wang Linjun , Wang Lin-Wang , Peng Xiaogang 
Published: April 2019

AbstractAuger recombination is the main non-radiative decay pathway for multi-carrier states of colloidal quantum dots, which affects performance of most of their optical and optoelectronic applications. Outstanding single-exciton properties of CdSe/CdS core/shell quantum dots enable us to simultaneously study the two basic types of Auger recombination channels—negative trion and positive trion channels. Though Auger rates of positive trion are regarded to be much faster than that of negative trion for II-VI quantum dots in literature, our experiments find the two rates can be inverted for certain core/shell geometries. This is confirmed by theoretical calculations as a result of geometry-dependent dielectric screening. By varying the core/shell geometry, both types of Auger rates can be independently tuned for ~ 1 order of magnitude. Experimental and theoretical findings shed new light on designing quantum dots with necessary Auger recombination characteristics for high-power light-emitting-diodes, lasers, single-molecular tracking, super-resolution microscope, and advanced quantum light sources.
SWITCH 1/DYAD is a WINGS APART-LIKE antagonist that maintains sister chromatid cohesion in meiosis
Authors: Yang Chao , Hamamura Yuki , Sofroni Kostika , Böwer Franziska , Stolze Sara Christina , Nakagami Hirofumi , Schnittger Arp 
Published: April 2019

AbstractMitosis and meiosis both rely on cohesin, which embraces the sister chromatids and plays a crucial role for the faithful distribution of chromosomes to daughter cells. Prior to the cleavage by Separase at anaphase onset, cohesin is largely removed from chromosomes by the non-proteolytic action of WINGS APART-LIKE (WAPL), a mechanism referred to as the prophase pathway. To prevent the premature loss of sister chromatid cohesion, WAPL is inhibited in early mitosis by Sororin. However, Sororin homologs have only been found to function as WAPL inhibitors during mitosis in vertebrates and Drosophila. Here we show that SWITCH 1/DYAD defines a WAPL antagonist that acts in meiosis of Arabidopsis. Crucially, SWI1 becomes dispensable for sister chromatid cohesion in the absence of WAPL. Despite the lack of any sequence similarities, we found that SWI1 is regulated and functions in a similar manner as Sororin hence likely representing a case of convergent molecular evolution across the eukaryotic kingdom.
A universal state and its relaxation mechanisms of long-range interacting polygons
Authors: Shen Hongchuan , Tong Hua , Tan Peng , Xu Lei 
Published: April 2019

AbstractUsing polygonal magnetic particles, we conduct experiments to explore the space-filling properties of anisotropic blocks with long-range interactions. In contrast to previous studies, we obtain the surprising finding that our systems’ structures do not depend on the shape of building blocks: a single state, the hexagonal plastic crystal, appears as a universal attractor for a wide range of different polygons. This robust particle-shape independency appears as the interactions go beyond nearest neighbors. Particle shape plays an essential role in system relaxation, and determines the basic relaxation dynamics through a microscopic control parameter, internal roughness, produced by particle vertices. Thus our study reveals a new pattern-forming paradigm, in which particle shape plays little role in the static structure but determines the essential relaxation dynamics. Due to the ubiquity of long-range interactions and anisotropic building blocks, our discovery may shed new light on diverse problems involving structure formation, self-assembly, and packing.
Gene discovery informatics toolkit defines candidate genes for unexplained infertility and prenatal or infantile mortality
Authors: Dawes Ruebena , Lek Monkol , Cooper Sandra T. 
Published: April 2019

AbstractDespite a recent surge in novel gene discovery, genetic causes of prenatal-lethal phenotypes remain poorly defined. To advance gene discovery in prenatal-lethal disorders, we created an easy-to-mine database integrating known human phenotypes with inheritance pattern, scores of genetic constraint, and murine and cellular knockout phenotypes—then critically assessed defining features of known prenatal-lethal genes, among 3187 OMIM genes, and relative to 16,009 non-disease genes. While around one-third (39%) of protein-coding genes are essential for murine development, we curate only 3% (624) of human protein-coding genes linked currently to prenatal/infantile lethal disorders. 75% prenatal-lethal genes are linked to developmental lethality in knockout mice, compared to 54% for all OMIM genes and 34% among non-disease genes. Genetic constraint correlates with inheritance pattern (autosomal recessive <<autosomal dominant <X-linked), and is greatest among prenatal-lethal genes. Importantly, >90% of recessive genes show neither missense nor loss-of-function constraint, even for prenatal-lethal genes. Detailed ontology mapping for 624 prenatal-lethal genes shows marked enrichment among dominant genes for nuclear proteins with roles in RNA/DNA biology, with recessive genes enriched in cytoplasmic (mitochondrial) metabolic proteins. We conclude that genes without genetic constraint should not be excluded as potential novel disease genes, and especially for recessive conditions (<10% constrained). Prenatal lethal genes are 5.9-fold more likely to be associated with a lethal murine phenotype than non-disease genes. Cell essential genes are largely a subset of mouse-lethal genes, notably under-represented among known OMIM genes, and strong candidates for gamete/embryo non-viability. We therefore curate 3435 ‘candidate developmental lethal’ human genes: essential for murine development or cellular viability, not yet linked to human disorders, presenting strong candidates for unexplained infertility and prenatal/infantile mortality.
Medusozoan genomes inform the evolution of the jellyfish body plan
Authors: Khalturin Konstantin , Shinzato Chuya , Khalturina Maria , Hamada Mayuko , Fujie Manabu , Koyanagi Ryo , Kanda Miyuki , Goto Hiroki , Anton-Erxleben Friederike , Toyokawa Masaya , Toshino Sho , Satoh Noriyuki 
Published: April 2019

AbstractCnidarians are astonishingly diverse in body form and lifestyle, including the presence of a jellyfish stage in medusozoans and its absence in anthozoans. Here, we sequence the genomes of Aurelia aurita (a scyphozoan) and Morbakka virulenta (a cubozoan) to understand the molecular mechanisms responsible for the origin of the jellyfish body plan. We show that the magnitude of genetic differences between the two jellyfish types is equivalent, on average, to the level of genetic differences between humans and sea urchins in the bilaterian lineage. About one-third of Aurelia genes with jellyfish-specific expression have no matches in the genomes of the coral and sea anemone, indicating that the polyp-to-jellyfish transition requires a combination of conserved and novel, medusozoa-specific genes. While no genomic region is specifically associated with the ability to produce a jellyfish stage, the arrangement of genes involved in the development of a nematocyte—a phylum-specific cell type—is highly structured and conserved in cnidarian genomes; thus, it represents a phylotypic gene cluster.
Morphology and genome of a snailfish from the Mariana Trench provide insights into deep-sea adaptation
Authors: Wang Kun , Shen Yanjun , Yang Yongzhi , Gan Xiaoni , Liu Guichun , Hu Kuang , Li Yongxin , Gao Zhaoming , Zhu Li , Yan Guoyong , He Lisheng , Shan Xiujuan , Yang Liandong , Lu Suxiang , Zeng Honghui , Pan Xiangyu , Liu Chang , Yuan Yuan , Feng Chenguang , Xu Wenjie , Zhu Chenglong , Xiao Wuhan , Dong Yang , Wang Wen , Qiu Qiang , He Shunping 
Published: April 2019

AbstractIt is largely unknown how living organisms—especially vertebrates—survive and thrive in the coldness, darkness and high pressures of the hadal zone. Here, we describe the unique morphology and genome ofPseudoliparis swirei—a recently described snailfish species living below a depth of 6,000 m in the Mariana Trench. Unlike closely related shallow sea species,P. swireihas transparent, unpigmented skin and scales, thin and incompletely ossified bones, an inflated stomach and a non-closed skull. Phylogenetic analyses show thatP. swireidiverged from a close relative living near the sea surface about 20 million years ago and has abundant genetic diversity. Genomic analyses reveal that: (1) the bone Gla protein (bglap) gene has a frameshift mutation that may cause early termination of cartilage calcification; (2) cell membrane fluidity and transport protein activity inP. swireimay have been enhanced by changes in protein sequences and gene expansion; and (3) the stability of its proteins may have been increased by critical mutations in the trimethylamineN-oxide-synthesizing enzyme and hsp90 chaperone protein. Our results provide insights into the morphological, physiological and molecular evolution of hadal vertebrates.
Ni(OH)2-decorated nitrogen doped MWCNT nanosheets as an efficient electrode for high performance supercapacitors
Authors: Ramesh Sivalingam , Karuppasamy K. , Yadav Hemraj M. , Lee Jae-Joon , Kim Hyun-Seok , Kim Heung-Soo , Kim Joo-Hyung 
Published: April 2019

AbstractIn this study, nickel hydroxide nanoparticles (NPs) decorated with nitrogen doped multiwalled carbon nanotubes (N-MWCNT) hybrid composite was synthesized by thermal reduction process in the presence of cetyl ammonium bromide (CTAB) and urea. The as-synthesized Ni(OH)2@N-MWCNT hybrid composite was characterized by FTIR, Raman, XRD, BET, BJH and FE-TEM analyses. These prepared porous carbon hybrid composite materials possessed high specific surface area and sheet like morphology useful for active electrode materials. The maximum specific capacitance of Ni(OH)2@N-MWCNT hybrid nanocomposite in the two electrode system showed 350 Fg−1 at 0.5 A/g,energy density ~43.75 Wkg−1 and corresponds to power density 1500 W kg−1 with excellent capacity retention after 5000 cycles. The results suggest that the prepared two-dimensional hybrid composite is a promising electrode material for electrochemical energy storage applications.