bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐Speed Video Observations of Recoil Leaders Producing and Not Producing Return Strokes in a Canton‐Tower Upward Flash
Authors: Wu Bin , Lyu Weitao , Qi Qi , Ma Ying , Chen Lyuwen , Jiang Ruijiao , Zhu Yanan , Rakov Vladimir A. 
Published: July 2019

AbstractHigh‐speed video and electric field change data have been used to examine the initiation and propagation of 21 recoil leaders, 7 of which evolved into dart (or dart‐stepped) leaders (DLs) initiating return strokes and 14 were attempted leaders (ALs), in a Canton‐Tower upward flash. Three DLs and two ALs clearly exhibited bidirectional extension. Each DL was preceded by one or more ALs and initiated near the extremity of the positive end of the preceding AL. The positive end of each bidirectional DL generally appeared to be inactive (stationary) or intermittently propagated along the positive part of the preceding AL channel and extended into the virgin air. A sequence of two floating channel segments was formed ahead of the approaching positive end of one DL, causing its abrupt elongation.
IRF1 is critical for the TNF-driven interferon response in rheumatoid fibroblast-like synoviocytes
Authors: Bonelli Michael , Dalwigk Karolina , Platzer Alexander , Olmos Calvo Isabel , Hayer Silvia , Niederreiter Birgit , Holinka Johannes , Sevelda Florian , Pap Thomas , Steiner Günter , Superti-Furga Giulio , Smolen Josef S. , Kiener Hans P. , Karonitsch Thomas 
Published: July 2019

AbstractRheumatoid arthritis (RA) is an autoimmune disease characterized by persistent synovial inflammation. The major drivers of synovial inflammation are cytokines and chemokines. Among these molecules, TNF activates fibroblast-like synoviocytes (FLSs), which leads to the production of inflammatory mediators. Here, we show that TNF regulates the expression of the transcription factor interferon regulatory factor 1 (IRF1) in human FLSs as well as in a TNF transgenic arthritis mouse model. Transcriptomic analyses of IRF1-deficient, TNF-stimulated FLSs define the interferon (IFN) pathway as a major target of IRF1. IRF1 expression is associated with the expression of IFNβ, which leads to the activation of the JAK-STAT pathway. Blocking the JAK-STAT pathway with the Janus kinase inhibitor (JAKinib) baricitinib or tofacitinib reduces the expression of IFN-regulated genes (IRGs) in TNF-activated FLSs. Therefore, we conclude that TNF induces a distinct inflammatory cascade, in which IRGs are key elements, in FLSs. The IFN-signature might be a promising biomarker for the efficient and personalized use of new treatment strategies for RA, such as JAKinibs.
Mechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: old actors and new players
Authors: Yuan Xiaotian , Larsson Catharina , Xu Dawei 
Published: July 2019

AbstractLong-lived species Homo sapiens have evolved robust protection mechanisms against cancer by repressing telomerase and maintaining short telomeres, thereby delaying the onset of the majority of cancer types until post-reproductive age. Indeed, telomerase is silent in most differentiated human cells, predominantly due to the transcriptional repression of its catalytic component telomerase reverse transcriptase (TERT) gene. The lack of telomerase/TERT expression leads to progressive telomere erosion in dividing human cells, whereas critically shortened telomere length induces a permanent growth arrest stage named replicative senescence. TERT/telomerase activation has been experimentally shown to be essential to cellular immortalization and malignant transformation by stabilizing telomere length and erasing the senescence barrier. Consistently, TERT expression/telomerase activity is detectable in up to 90% of human primary cancers. Compelling evidence has also accumulated that TERT contributes to cancer development and progression via multiple activities beyond its canonical telomere-lengthening function. Given these key roles of telomerase and TERT in oncogenesis, great efforts have been made to decipher mechanisms underlying telomerase activation and TERT induction. In the last two decades since the TERT gene and promoter were cloned, the derepression of the TERT gene has been shown to be achieved typically at a transcriptional level through dysregulation of oncogenic factors or signaling, post-transcriptional/translational regulation and genomic amplification. However, advances in high-throughput next-generation sequencing technologies have prompted a revolution in cancer genomics, which leads to the recent discovery that genomic alterations take center stage in activating the TERT gene. In this review article, we summarize critical mechanisms activating TERT transcription, with special emphases on the contribution of TERT promoter mutations and structural alterations at the TERT locus, and briefly discuss the underlying implications of these genomic events-driven TERT hyperactivity in cancer initiation/progression and potential clinical applications as well.
The role of GPCRs in bone diseases and dysfunctions
Authors: Luo Jian , Sun Peng , Siwko Stefan , Liu Mingyao , Xiao Jianru 
Published: July 2019

AbstractThe superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals. Critical roles of GPCRs have been established in bone development, remodeling, and disease. Multiple human GPCR mutations impair bone development or metabolism, resulting in osteopathologies. Here we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in animals. To date, 92 receptors (5 glutamate family, 67 rhodopsin family, 5 adhesion, 4 frizzled/taste2 family, 5 secretin family, and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals). By analyzing data from these 92 GPCRs, we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions, and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal models. Data from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD: 9 genes each for human height and osteoporosis; 4 genes each for human osteoarthritis (OA) and fracture risk; and 2 genes each for adolescent idiopathic scoliosis (AIS), periodontitis, osteosarcoma growth, and tooth development. Reports from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass, while deficiency of 22 GPCRs increased bone mass and BMD; deficiency of 8 GPCRs reduced body length, while 5 mice had reduced femur size upon GPCR deletion. Furthermore, deficiency in 6 GPCRs induced osteoporosis; 4 induced osteoarthritis; 3 delayed fracture healing; 3 reduced arthritis severity; and reduced bone strength, increased bone strength, and increased cortical thickness were each observed in 2 GPCR-deficiency models. The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis, population studies, and investigation of phenotype correlation with SNPs to elucidate GPCR function in human diseases.
C1q-TNF-related protein-3 attenuates pressure overload-induced cardiac hypertrophy by suppressing the p38/CREB pathway and p38-induced ER stress
Authors: Zhang Bing , Zhang Ping , Tan Yanzhen , Feng Pan , Zhang Zhengbin , Liang Hongliang , Duan Weixun , Jin Zhenxiao , Wang Xiaowu , Liu Jincheng , Gao Erhe , Yu Shiqiang , Yi Dinghua , Sun Yang , Yi Wei 
Published: July 2019

AbstractC1q-tumor necrosis factor-related protein-3 (CTRP3) is an adipokine, which exerts protective function in ischemic or diabetic heart injury. However, the role of CTRP3 in cardiac hypertrophy remains unclear. The aim of this study was to investigate the pharmacological effects of CTRP3 on pathological cardiac hypertrophy induced by hypertension. Male C57BL/6 J wild-type (WT) mice, Ctrp3 knockout mice, and mice infected with lentivirus overexpressing mouse Ctrp3 underwent sham surgery or transverse aortic constriction (TAC) surgery. After 4 weeks, cardiac hypertrophy, fibrosis, and cardiac function were examined. Compared with WT mice, Ctrp3 deficiency substantially impaired contractile dysfunction, exacerbated the enlargement of cardiomyocytes and myocardial fibrosis, and reprogramed the expression of pathological genes after TAC. Conversely, CTRP3 overexpression played a role in restoring the left ventricular cardiac contractile function, alleviating cardiac hypertrophy and fibrosis, and inhibiting the expression of hypertrophic and fibrotic signaling in mice after TAC. Furthermore, CTRP3 regulated the expression of the p38/CREB pathway and of the primary modulating factors of the endoplasmic reticulum stress, i.e., GRP78 and the downstream molecules eukaryotic translation inhibition factor 2 submit α, C/EBP homologous protein, and inositol-requiring enzyme-1. Further, inhibition of p38 MAPK by SB203580 blunted the ER stress intensified by Ctrp3 deficiency. In vitro, CTRP3 protected neonatal rat cardiac myocytes against phenylephrine-induced cardiomyocyte hypertrophy. We conclude that CTRP3 protects the host against pathological cardiac remodeling and left ventricular dysfunction induced by pressure overload largely by inhibiting the p38/CREB pathway and alleviating p38-induced ER stress.
EZH2, JMJD3, and UTX epigenetically regulate hepatic plasticity inducing retro-differentiation and proliferation of liver cells
Authors: Pediconi Natalia , Salerno Debora , Lupacchini Leonardo , Angrisani Annapaola , Peruzzi Giovanna , De Smaele Enrico , Levrero Massimo , Belloni Laura 
Published: July 2019

AbstractModification of histones by lysine methylation plays a role in many biological processes, and it is dynamically regulated by several histone methyltransferases and demethylases. The polycomb repressive complex contains the H3K27 methyltransferase EZH2 and controls dimethylation and trimethylation of H3K27 (H3K27me2/3), which trigger gene suppression. JMJD3 and UTX have been identified as H3K27 demethylases that catalyze the demethylation of H3K27me2/3, which in turns lead to gene transcriptional activation. EZH2, JMJD3 and UTX have been extensively studied for their involvement in development, immune system, neurodegenerative disease, and cancer. However, their role in molecular mechanisms underlying the differentiation process of hepatic cells is yet to be elucidated. Here, we show that EZH2 methyltransferase and JMJD3/UTX demethylases were deregulated during hepatic differentiation of human HepaRG cells resulting in a strong reduction of H3K27 methylation levels. Inhibition of JMJD3 and UTX H3K27 demethylase activity by GSK-J4 epi-drug reverted phenotype of HepaRG DMSO-differentiated cells and human primary hepatocytes, drastically decreasing expression of hepatic markers and inducing cell proliferation. In parallel, inhibition of EZH2 H3K27me3 activity by GSK-126 epi-drug induced upregulation of hepatic markers and downregulated the expression of cell cycle inhibitor genes. To conclude, we demonstrated that modulation of H3K27 methylation by inhibiting methyl-transferase and dimethyl-transferase activity influences the differentiation status of hepatic cells, identifying a possible new role of EZH2, JMJD3 and UTX epi-drugs to modulate hepatic cell plasticity.
Apogossypol-mediated reorganisation of the endoplasmic reticulum antagonises mitochondrial fission and apoptosis
Authors: Yedida Govindaraju , Milani Mateus , Cohen Gerald M , Varadarajan Shankar 
Published: July 2019

AbstractThe endoplasmic reticulum (ER) with its elaborate network of highly curved tubules and flat sheets interacts with several other organelles, including mitochondria, peroxisomes and endosomes, to play vital roles in their membrane dynamics and functions. Previously, we identified structurally diverse chemicals from different pharmacological classes, which induce a reversible reorganisation of ER membranes. Using apogossypol as a prototypic tool compound, we now show that ER membrane reorganisation occurs at the level of ER tubules but does not involve ER sheets. Reorganisation of ER membranes prevents DRP-1-mediated mitochondrial fission, thereby antagonising the functions of several mitochondrial fission-inducing agents. Previous reports have suggested that ER membranes mark the constriction sites of mitochondria by localising DRP-1, as well as BAX on mitochondrial membranes to facilitate both mitochondrial fission and outer membrane permeabilisation. Following ER membrane reorganisation and subsequent exposure to an apoptotic stimulus (BH3 mimetics), DRP-1 still colocalises with the reorganised ER membranes but BAX translocation and activation, cytochrome c release and phosphatidylserine externalisation are all inhibited, thereby diminishing the ability of BH3 mimetics to induce the intrinsic apoptotic pathway. Strikingly, both ER membrane reorganisation and its resulting inhibition of apoptosis could be reversed by inhibitors of dihydroorotate dehydrogenase (DHODH), namely teriflunomide and its active metabolite, leflunomide. However, neither genetic inhibition of DHODH using RNA interference nor metabolic supplementation with orotate or uridine to circumvent the consequences of a loss of DHODH activity rescued the effects of DHODH inhibitors, suggesting that the effects of these inhibitors in preventing ER membrane reorganisation is most likely independent of their ability to antagonise DHODH activity. Our results strengthen the hypothesis that ER is fundamental for key mitochondrial functions, such as fusion-fission dynamics and apoptosis.
Paradoxical impact of memory on color appearance of faces
Authors: Hasantash Maryam , Lafer-Sousa Rosa , Afraz Arash , Conway Bevil R. 
Published: July 2019

AbstractWhat is color vision for? Here we compared the extent to which memory modulates color appearance of objects and faces. Participants matched the colors of stimuli illuminated by low-pressure sodium light, which renders scenes monochromatic. Matches for fruit were not predicted by stimulus identity. In contrast, matches for faces were predictable, but surprising: faces appeared green and looked sick. The paradoxical face-color percept could be explained by a Bayesian observer model constrained by efficient coding. The color-matching data suggest that the face-color prior is established by visual signals arising from the recently evolved L-M cone system, not the older S-cone channel. Taken together, the results show that when retinal mechanisms of color vision are impaired, the impact of memory on color perception is greatest for face color, supporting the idea that trichromatic color plays an important role in social communication.
Adhesion of two-dimensional titanium carbides (MXenes) and graphene to silicon
Authors: Li Yanxiao , Huang Shuohan , Wei Congjie , Wu Chenglin , Mochalin Vadym N. 
Published: July 2019

AbstractTwo-dimensional transition metal carbides (MXenes) have attracted a great interest of the research community as a relatively recently discovered large class of materials with unique electronic and optical properties. Understanding of adhesion between MXenes and various substrates is critically important for MXene device fabrication and performance. We report results of direct atomic force microscopy (AFM) measurements of adhesion of two MXenes (Ti3C2Tx and Ti2CTx) with a SiO2 coated Si spherical tip. The Maugis-Dugdale theory was applied to convert the AFM measured adhesion force to adhesion energy, while taking into account surface roughness. The obtained adhesion energies were compared with those for mono-, bi-, and tri-layer graphene, as well as SiO2 substrates. The average adhesion energies for the MXenes are 0.90 ± 0.03 J m−2 and 0.40 ± 0.02 J m−2 for thicker Ti3C2Tx and thinner Ti2CTx, respectively, which is of the same order of magnitude as that between graphene and silica tip.
Interseismic strain build-up on the submarine North Anatolian Fault offshore Istanbul
Authors: Lange Dietrich , Kopp Heidrun , Royer Jean-Yves , Henry Pierre , Çakir Ziyadin , Petersen Florian , Sakic Pierre , Ballu Valerie , Bialas Jörg , Özeren Mehmet Sinan , Ergintav Semih , Géli Louis 
Published: July 2019

AbstractUsing offshore geodetic observations, we show that a segment of the North Anatolian Fault in the central Sea of Marmara is locked and therefore accumulating strain. The strain accumulation along this fault segment was previously extrapolated from onshore observations or inferred from the absence of seismicity, but both methods could not distinguish between fully locked or fully creeping fault behavior. A network of acoustic transponders measured crustal deformation with mm-precision on the seafloor for 2.5 years and did not detect any significant fault displacement. Absence of deformation together with sparse seismicity monitored by ocean bottom seismometers indicates complete fault locking to at least 3 km depth and presumably into the crystalline basement. The slip-deficit of at least 4 m since the last known rupture in 1766 is equivalent to an earthquake of magnitude 7.1 to 7.4 in the Sea of Marmara offshore metropolitan Istanbul.
Chemical genomics reveals histone deacetylases are required for core regulatory transcription
Authors: Gryder Berkley E. , Wu Lei , Woldemichael Girma M. , Pomella Silvia , Quinn Taylor R. , Park Paul M. C. , Cleveland Abigail , Stanton Benjamin Z. , Song Young , Rota Rossella , Wiest Olaf , Yohe Marielle E. , Shern Jack F. , Qi Jun , Khan Javed 
Published: July 2019

AbstractIdentity determining transcription factors (TFs), or core regulatory (CR) TFs, are governed by cell-type specific super enhancers (SEs). Drugs to selectively inhibit CR circuitry are of high interest for cancer treatment. In alveolar rhabdomyosarcoma, PAX3-FOXO1 activates SEs to induce the expression of other CR TFs, providing a model system for studying cancer cell addiction to CR transcription. Using chemical genetics, the systematic screening of chemical matter for a biological outcome, here we report on a screen for epigenetic chemical probes able to distinguish between SE-driven transcription and constitutive transcription. We find that chemical probes along the acetylation-axis, and not the methylation-axis, selectively disrupt CR transcription. Additionally, we find that histone deacetylases (HDACs) are essential for CR TF transcription. We further dissect the contribution of HDAC isoforms using selective inhibitors, including the newly developed selective HDAC3 inhibitor LW3. We show HDAC1/2/3 are the co-essential isoforms that when co-inhibited halt CR transcription, making CR TF sites hyper-accessible and disrupting chromatin looping.
Dietary intervention of mice using an improved Multiple Artificial-gravity Research System (MARS) under artificial 1 g
Authors: Matsuda Chie , Kato Tamotsu , Inoue-Suzuki Sayo , Kikuchi Jun , Ohta Toshiko , Kagawa Masaharu , Hattori Masahira , Kobayashi Hiroe , Shiba Dai , Shirakawa Masaki , Mizuno Hiroyasu , Furukawa Satoshi , Mukai Chiaki , Ohno Hiroshi 
Published: July 2019

AbstractJapan Aerospace Exploration Agency (JAXA) has developed mouse habitat cage units equipped with an artificial gravity-producing centrifuge, called the Multiple Artificial-gravity Research System (MARS), that enables single housing of a mouse under artificial gravity (AG) in orbit. This is a report on a hardware evaluation. The MARS underwent improvement in water leakage under microgravity (MG), and was used in the second JAXA mouse mission to evaluate the effect of AG and diet on mouse biological system simultaneously. Twelve mice were divided into four groups of three, with each group fed a diet either with or without fructo-oligosaccharide and housed singly either at 1 g AG or MG for 30 days on the International Space Station, then safely returned to the Earth. Body weight tended to increase in AG mice and decrease in MG mice after spaceflight, but these differences were not significant. This indicates that the improved MARS may be useful in evaluating AG and dietary intervention for space flown mice.
Microgravity disturbance analysis on Chinese space laboratory
Authors: Dong Wenbo , Duan Wenxiang , Liu Wei , Zhang Yongkang 
Published: July 2019

AbstractMany scientific experiments are conducted in space; therefore, it is critical to understand the microgravity environment of a space laboratory. The first Chinese cargo ship, Tianzhou-1 (TZ-1), entered space on 20 April, 2017 and later joined with the Tiangong-2 (TG-2) Chinese space laboratory. TZ-1 carried a high-precision electrostatic suspension accelerometer system (ES-ACC) for measuring the microgravity acceleration on the spacecraft and a microgravity-active vibration system (MAIS), which contained flexible quartz accelerometers (Q-ACC). The ES-ACC was able to provide a reduced-disturbance environment for the MAIS. The purpose of these two instruments was to validate novel technologies and as an opportunity to record the microgravity acceleration of TZ-1 and TG-2 in detail during spacecraft operation in different flight modes, with or without vibration isolation. The acceleration data were analyzed comprehensively in a time–frequency–amplitude spectrogram. Some periodical disturbances with orbital period and irregular signals related to certain in-orbit events were observed. After reducing those disturbances, the microgravity levels on TZ-1 and TG-2 could be resolved to better than 10−6 m/s2 in the root mean square in the frequency of 0.01–10 Hz. These accurate measurements aboard the Chinese space laboratory will provide valuable information to optimize working conditions for scientific experiments.
AgBR1 antibodies delay lethal Aedes aegypti-borne West Nile virus infection in mice
Authors: Uraki Ryuta , Hastings Andrew K. , Brackney Doug E. , Armstrong Philip M. , Fikrig Erol 
Published: July 2019

AbstractWest Nile virus (WNV) is transmitted by mosquitoes and can cause severe disease, including meningoencephalitis. AgBR1 is a mosquito salivary protein that enhances Aedes aegypti mosquito-borne Zika virus pathogenesis in mice. Here, we show that AgBR1 antibodies reduce the initial West Nile viral load and delay lethal infection after feeding by an infected Aedes aegypti mosquito. Targeting AgBR1 may therefore be incorporated into strategies to prevent mosquito-transmitted West Nile virus infection.