bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lateral Particle Supply as a Key Vector in the Oceanic Carbon Cycle
Authors: Kim Minkyoung , Hwang Jeomshik , Eglinton Timothy I. , Druffel Ellen R. M. 
Published: August 2020

AbstractThe export of particulate organic carbon (POC) from surface waters to the ocean interior via the biological carbon pump is largely envisioned as a vertical process. However, several lines of evidence suggest that lateral supply of aged organic matter hosted on lithogenic particles derived from sediment resuspension may also be a significant process. Despite its potential importance, lateral POC supply has not been systematically examined on a global scale. Here, we assess the contribution of resuspended sediment to sinking particulate matter in the ocean using literature data of sediment trap studies. Proportions and absolute fluxes of lithogenic material at 158 sites and available radiocarbon contents are compiled to develop a global‐scale assessment. We find that lithogenic material accounts for 25 ± 20% of sinking particulate matter, comprising a mean flux of 67 mg m−2d−1. Lithogenic material flux generally decreased with increasing distance from the coast and with increasing height above the seafloor. The Δ14C values of POC exhibited a linear relationship with a wt/wt ratio of lithogenic material to POC. Loadings of aged POC to lithogenic material obtained from this relationship were similar to or higher than POC content of the surface sediment in the vicinity. Based on this relationship, and the global mean of lithogenic material content of sinking particulate matter, we calculate that aged POC from sediment resuspension comprises 0.2–0.7% of sinking particles and 4–11% of sinking POC intercepted by sediment traps.
Geomagnetic Effects in Spatial Distributions of Particle Precipitation in Terms of Particle Energy Channels
Authors: Shen Han‐Wen , Shue Jih‐Hong , Dombeck John , Li Hsien‐Ming 
Published: August 2020

AbstractThis study examines the spatial distributions of precipitation during active and quiet times. Most previous studies commonly classified precipitation into different energy spectral types, but we utilized a classification according to particle energy channels. A general conclusion derived from these distributions suggests that regardless of active and quiet times, low‐energy (<1 keV) and high‐energy precipitating particles are mostly on the dayside and nightside, respectively. A comparison with past results reveals that the high‐energy electron precipitation during quiet times is mostly due to wave scattering and that during active times is mainly produced by quasi‐static potential structures (QSPS) and Alfvénic acceleration, while low‐energy electron precipitation is mostly caused by QSPS and Alfvénic acceleration regardless of quiet and active times. For both high‐energy proton and electron precipitation, the nightside dawn‐dusk asymmetry of their distributions during active times is found to be opposite of that during quiet times. We infer that the distribution of high‐energy precipitation during quiet times is dominated by the curvature and gradient drifts, while during active times it is mainly due to the physical processes or phenomena related to substorms in the magnetotail. Empirical orthogonal function analysis has been applied in this study to derive where the flux has the maximum enhancement as the geomagnetic activity increases. The results further demonstrate that low‐energy and high‐energy protons mainly increase in the noon and postmidnight sectors, respectively. The highest enhancements of low‐energy and high‐energy electrons are in the prenoon and premidnight sectors, respectively.
The proapoptotic gene interferon regulatory factor-1 mediates the antiproliferative outcome of paired box 2 gene and tamoxifen
Authors: Wang Shixiong , Somisetty Venkata S. , Bai Baoyan , Chernukhin Igor , Niskanen Henri , Kaikkonen Minna U. , Bellet Meritxell , Carroll Jason S. , Hurtado Antoni 
Published: August 2020

AbstractTamoxifen is the most prescribed selective estrogen receptor (ER) modulator in patients with ER-positive breast cancers. Tamoxifen requires the transcription factor paired box 2 protein (PAX2) to repress the transcription of ERBB2/HER2. Now, we identified that PAX2 inhibits cell growth of ER+/HER2− tumor cells in a dose-dependent manner. Moreover, we have identified that cell growth inhibition can be achieved by expressing moderate levels of PAX2 in combination with tamoxifen treatment. Global run-on sequencing of cells overexpressing PAX2, when coupled with PAX2 ChIP-seq, identified common targets regulated by both PAX2 and tamoxifen. The data revealed that PAX2 can inhibit estrogen-induced gene transcription and this effect is enhanced by tamoxifen, suggesting that they converge on repression of the same targets. Moreover, PAX2 and tamoxifen have an additive effect and both induce coding genes and enhancer RNAs (eRNAs). PAX2–tamoxifen upregulated genes are also enriched with PAX2 eRNAs. The enrichment of eRNAs is associated with the highest expression of genes that positivity regulate apoptotic processes. In luminal tumors, the expression of a subset of these proapoptotic genes predicts good outcome and their expression are significantly reduced in tumors of patients with relapse to tamoxifen treatment. Mechanistically, PAX2 and tamoxifen coexert an antitumoral effect by maintaining high levels of transcription of tumor suppressors that promote cell death. The apoptotic effect is mediated in large part by the gene interferon regulatory factor 1. Altogether, we conclude that PAX2 contributes to better clinical outcome in tamoxifen treated ER-positive breast cancer patients by repressing estrogen signaling and inducing cell death related pathways.
Pharmacogenomics cascade testing (PhaCT): a novel approach for preemptive pharmacogenomics testing to optimize medication therapy
Authors: Roosan Don , Hwang Angela , Roosan Moom R. 
Published: August 2020

AbstractThe implementation of pharmacogenomics (PGx) has come a long way since the dawn of utilizing pharmacogenomic data in clinical patient care. However, the potential benefits of sharing PGx results have yet to be explored. In this paper, we explore the willingness of patients to share PGx results, as well as the inclusion of family medication history in identifying potential family members for pharmacogenomics cascade testing (PhaCT). The genetic similarities in families allow for identifying potential gene variants prior to official preemptive testing. Once a candidate patient is determined, PhaCT can be initiated. PhaCT recognizes that further cascade testing throughout a family can serve to improve precision medicine. In order to make PhaCT feasible, we propose a novel shareable HIPAA-compliant informatics platform that will enable patients to manage not only their own test results and medications but also those of their family members. The informatics platform will be an external genomics system with capabilities to integrate with patients’ electronic health records. Patients will be given the tools to provide information to and work with clinicians in identifying family members for PhaCT through this platform. Offering patients the tools to share PGx results with their family members for preemptive testing could be the key to empowering patients. Clinicians can utilize PhaCT to potentially improve medication adherence, which may consequently help to distribute the burden of health management between patients, family members, providers, and payers.
The BCL-2 selective inhibitor ABT-199 sensitizes soft tissue sarcomas to proteasome inhibition by a concerted mechanism requiring BAX and NOXA
Authors: Muenchow Alina , Weller Sandra , Hinterleitner Clemens , Malenke Elke , Bugl Stefanie , Wirths Stefan , Müller Martin R. , Schulze-Osthoff Klaus , Aulitzky Walter E. , Kopp Hans-Georg , Essmann Frank 
Published: August 2020

AbstractSoft tissue sarcomas (STS) are a heterogeneous group of malignancies predominantly affecting children and young adults. Despite improvements in multimodal therapies, 5-year survival rates are only 50% and new treatment options in STS are urgently needed. To develop a rational combination therapy for the treatment of STS we focused on ABT-199 (Venetoclax), a BCL-2 specific BH3-mimetic, in combination with the proteasome inhibitor bortezomib (BZB). Simultaneous inhibition of BCL-2 and the proteasome resulted in strongly synergistic apoptosis induction. Mechanistically, ABT-199 mainly affected the multidomain effector BAX by liberating it from BCL-2 inhibition. The combination with BZB additionally resulted in the accumulation of BOK, a BAX/BAK homologue, and of the BH3-only protein NOXA, which inhibits the anti-apoptotic protein MCL-1. Thus, the combination of ABT-199 and BZB sensitizes STS cells to apoptosis by simultaneously releasing several defined apoptotic restraints. This synergistic mechanism of action was verified by CRISPR/Cas9 knock-out, showing that both BAX and NOXA are crucial for ABT-199/BZB-induced apoptosis. Noteworthy, efficient induction of apoptosis by ABT-199/BZB was not affected by the p53 status and invariably detected in cell lines and patient-derived tumor cells of several sarcoma types, including rhabdomyo-, leiomyo-, lipo-, chondro-, osteo-, or synovial sarcomas. Hence, we propose the combination of ABT-199 and BZB as a promising strategy for the treatment of STS, which should warrant further clinical investigation.
KIN10 promotes stomatal development through stabilization of the SPEECHLESS transcription factor
Authors: Han Chao , Liu Yue , Shi Wen , Qiao Yan , Wang Lingyan , Tian Yanchen , Fan Min , Deng Zhiping , Lau On Sun , De Jaeger Geert , Bai Ming-Yi 
Published: August 2020

AbstractStomata are epidermal structures that modulate gas exchanges between plants and the atmosphere. The formation of stomata is regulated by multiple developmental and environmental signals, but how these signals are coordinated to control this process remains unclear. Here, we showed that the conserved energy sensor kinase SnRK1 promotes stomatal development under short-day photoperiod or in liquid culture conditions. Mutation of KIN10, the catalytic α-subunit of SnRK1, results in the decreased stomatal index; while overexpression of KIN10 significantly induces stomatal development. KIN10 displays the cell-type-specific subcellular location pattern. The nuclear-localized KIN10 proteins are highly enriched in the stomatal lineage cells to phosphorylate and stabilize SPEECHLESS, a master regulator of stomatal formation, thereby promoting stomatal development. Our work identifies a module links connecting the energy signaling and stomatal development and reveals that multiple regulatory mechanisms are in place for SnRK1 to modulate stomatal development in response to changing environments.
Single cell transcriptomics of human epidermis identifies basal stem cell transition states
Authors: Wang Shuxiong , Drummond Michael L. , Guerrero-Juarez Christian F. , Tarapore Eric , MacLean Adam L. , Stabell Adam R. , Wu Stephanie C. , Gutierrez Guadalupe , That Bao T. , Benavente Claudia A. , Nie Qing , Atwood Scott X. 
Published: August 2020

AbstractHow stem cells give rise to epidermis is unclear despite the crucial role the epidermis plays in barrier and appendage formation. Here we use single cell-RNA sequencing to interrogate basal stem cell heterogeneity of human interfollicular epidermis and find four spatially distinct stem cell populations at the top and bottom of rete ridges and transitional positions between the basal and suprabasal epidermal layers. Cell-cell communication modeling suggests that basal cell populations serve as crucial signaling hubs to maintain epidermal communication. Combining pseudotime, RNA velocity, and cellular entropy analyses point to a hierarchical differentiation lineage supporting multi-stem cell interfollicular epidermal homeostasis models and suggest that transitional basal stem cells are stable states essential for proper stratification. Finally, alterations in differentially expressed transitional basal stem cell genes result in severe thinning of human skin equivalents, validating their essential role in epidermal homeostasis and reinforcing the critical nature of basal stem cell heterogeneity.
DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans
Authors: Suen Kin Man , Braukmann Fabian , Butler Richard , Bensaddek Dalila , Akay Alper , Lin Chi-Chuan , Milonaitytė Dovilė , Doshi Neel , Sapetschnig Alexandra , Lamond Angus , Ladbury John Edward , Miska Eric Alexander 
Published: August 2020

AbstractMembraneless organelles are sites for RNA biology including small non-coding RNA (ncRNA) mediated gene silencing. How small ncRNAs utilise phase separated environments for their function is unclear. We investigated how the PIWI-interacting RNA (piRNA) pathway engages with the membraneless organelle P granule in Caenorhabditis elegans. Proteomic analysis of the PIWI protein PRG-1 reveals an interaction with the constitutive P granule protein DEPS-1. DEPS-1 is not required for piRNA biogenesis but piRNA-dependent silencing: deps-1 mutants fail to produce the secondary endo-siRNAs required for the silencing of piRNA targets. We identify a motif on DEPS-1 which mediates a direct interaction with PRG-1. DEPS-1 and PRG-1 form intertwining clusters to build elongated condensates in vivo which are dependent on the Piwi-interacting motif of DEPS-1. Additionally, we identify EDG-1 as an interactor of DEPS-1 and PRG-1. Our study reveals how specific protein-protein interactions drive the spatial organisation and piRNA-dependent silencing within membraneless organelles.
Human transcription factor and protein kinase gene fusions in human cancer
Authors: Salokas Kari , Weldatsadik Rigbe G. , Varjosalo Markku 
Published: August 2020

AbstractOncogenic gene fusions are estimated to account for up-to 20% of cancer morbidity. Recently sequence-level studies have established oncofusions throughout all tissue types. However, the functional implications of the identified oncofusions have often not been investigated. In this study, identified oncofusions from a fusion detection approach (DEEPEST) were analyzed in detail. Of the 28,863 oncofusions, we found almost 30% are expected to produce functional proteins with features from both parent genes. Kinases and transcription factors were the main gene families of the protein producing fusions. Considering their role as initiators, actors, and termination points of cellular signaling pathways, we focused our in-depth analyses on them. Domain architecture of the fusions and their wild-type interactors suggests that abnormal molecular context of protein domains caused by fusion events may unlock the oncogenic potential of the wild type counterparts of the fusion proteins. To understand overall oncofusion effects, we performed differential expression analysis using TCGA cancer project samples. Results indicated oncofusion-specific alterations in gene expression levels, and lower expression levels of components of key cellular pathways, in particular signal transduction and transcription regulation. The sum of results suggests that kinase and transcription factor oncofusions deregulate cellular signaling, possibly via acquiring novel functions.
Discovery of chemical markers for improving the quality and safety control of Sinomenium acutum stem by the simultaneous determination of multiple alkaloids using UHPLC-QQQ-MS/MS
Authors: Huang Yu-Feng , He Fan , Wang Can-Jian , Xie Ying , Zhang Yan-Yu , Sang Zhen , Qiu Ping , Luo Pei , Xiao Sheng-Yuan , Li Jing , Wu Fei-Ci , Liu Liang , Zhou Hua 
Published: August 2020

AbstractSinomenium acutum stem is a popular traditional Chinese medicine used to treat bone and joint diseases. Sinomenine is considered the only chemical marker for the quality control of S. acutum stem in mainstream pharmacopeias. However, higenamine in S. acutum stem is a novel stimulant that was banned by the World Anti-Doping Agency in 2017. Therefore, enhancing the quality and safety control of S. acutum stem to avoid potential safety risks is of utmost importance. In this study, a fast, sensitive, precise, and accurate method for the simultaneous determination of 11 alkaloids in S. acutum stem by ultrahigh-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-QQQ-MS/MS) was established. This method successfully analyzed thirty-five batches of S. acutum stem samples. The average contents of sinomenine, magnoflorine, coclaurine, acutumine, higenamine, sinoacutine, palmatine, magnocurarine, columbamine, 8-oxypalmatine, and jatrorrhizine were 24.9 mg/g, 6.35 mg/g, 435 μg/g, 435 μg/g, 288 μg/g, 44.4 μg/g, 22.5 μg/g, 21.1 μg/g, 15.8 μg/g, 9.30 μg/g, and 8.75 μg/g, respectively. Multivariate analysis, including principal component analysis (PCA), orthogonal partial least square method-discriminant analysis (OPLS-DA), and hierarchical cluster analysis (HCA), were performed to characterize the importance and differences among these alkaloids in S. acutum stem samples. As a result, sinomenine, magnoflorine, coclaurine, acutumine, and higenamine are proposed as chemical markers for quality control. Higenamine and coclaurine are also recommended as chemical markers for safety control. This report provides five alkaloids that can be used as chemical markers for improving the quality and safety control of S. acutum stem. It also alerts athletes to avoid the risks associated with consuming S. acutum stem.
The small compound, TD-198946, protects against intervertebral degeneration by enhancing glycosaminoglycan synthesis in nucleus pulposus cells
Authors: Kushioka Junichi , Kaito Takashi , Chijimatsu Ryota , Okada Rintaro , Ishiguro Hiroyuki , Bal Zeynep , Kodama Joe , Yano Fumiko , Saito Taku , Chung Ung-il , Tanaka Sakae , Yoshikawa Hideki 
Published: August 2020

AbstractDegeneration of the nucleus pulposus (NP) might serve as a trigger for intervertebral disc degeneration (IDD). A recent drug screening study revealed that the thienoindazole derivative, TD-198946, is a novel drug for the treatment of osteoarthritis. Because of the environmental and functional similarities between articular cartilage and intervertebral disc, TD-198946 is expected to prevent IDD. Herein, we sought to evaluate the effects of TD-198946 on IDD. TD-198946 enhanced glycosaminoglycan (GAG) production and the related genes in mouse NP cells and human NP cells (hNPCs). Further, Kyoto Encyclopedia of Genes and Genomes pathway analysis using the mRNA sequence of hNPCs suggested that the mechanism of action of TD-198946 primarily occurred via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The Akt inhibitor suppressed the enhancement of GAG production induced by TD-198946. The effects of TD-198946 on IDD at two different time points (immediate treatment model, immediately after the puncture; latent treatment model, 2 weeks after the puncture) were investigated using a mouse tail-disc puncture model. At both time points, TD-198946 prevented a loss in disc height. Histological analysis also demonstrated the preservation of the NP structures. TD-198946 exhibited therapeutic effects on IDD by enhancing GAG production via PI3K/Akt signaling.
Molecular mechanism of mitochondrial phosphatidate transfer by Ups1
Authors: Lu Jiuwei , Chan Chun , Yu Leiye , Fan Jun , Sun Fei , Zhai Yujia 
Published: August 2020

AbstractCardiolipin, an essential mitochondrial physiological regulator, is synthesized from phosphatidic acid (PA) in the inner mitochondrial membrane (IMM). PA is synthesized in the endoplasmic reticulum and transferred to the IMM via the outer mitochondrial membrane (OMM) under mediation by the Ups1/Mdm35 protein family. Despite the availability of numerous crystal structures, the detailed mechanism underlying PA transfer between mitochondrial membranes remains unclear. Here, a model of Ups1/Mdm35-membrane interaction is established using combined crystallographic data, all-atom molecular dynamics simulations, extensive structural comparisons, and biophysical assays. The α2-loop, L2-loop, and α3 helix of Ups1 mediate membrane interactions. Moreover, non-complexed Ups1 on membranes is found to be a key transition state for PA transfer. The membrane-bound non-complexed Ups1/ membrane-bound Ups1 ratio, which can be regulated by environmental pH, is inversely correlated with the PA transfer activity of Ups1/Mdm35. These results demonstrate a new model of the fine conformational changes of Ups1/Mdm35 during PA transfer.
Chiral lanthanide lumino-glass for a circularly polarized light security device
Authors: Kitagawa Yuichi , Wada Satoshi , Islam M. D. Jahidul , Saita Kenichiro , Gon Masayuki , Fushimi Koji , Tanaka Kazuo , Maeda Satoshi , Hasegawa Yasuchika 
Published: August 2020

AbstractArtificial light plays an essential role in information technologies such as optical telecommunications, data storage, security features, and the display of information. Here, we show a chiral lanthanide lumino-glass with extra-large circularly polarized luminescence (CPL) for advanced photonic security device applications. The chiral lanthanide glass is composed of a europium complex with the chiral (+)-3-(trifluoroacetyl)camphor ligand and the achiral glass promoter tris(2,6-dimethoxyphenyl)phosphine oxide ligand. The glass phase transition behavior of the Eu(III) complex is characterized using differential scanning calorimetry. The transparent amorphous glass shows CPL with extra-large dissymmetry factor of gCPL = 1.2. The brightness of the lumino-glass is one thousand times larger than that of Eu(III) luminophores embedded in polymer films of the same thickness at a Eu(III) concentration of 1 mM. The application of the chiral lanthanide lumino-glass in an advanced security paint is demonstrated.
Progenitor properties of type II supernovae: fitting to hydrodynamical models using Markov chain Monte Carlo methods
Authors: Martinez L. , Bersten M. C. , Anderson J. P. , González-Gaitán S. , Förster F. , Folatelli G. 
Published: August 2020

Context.The progenitor and explosion properties of type II supernovae (SNe II) are fundamental to understanding the evolution of massive stars. Particular attention has been paid to the initial masses of their progenitors, but despite the efforts made, the range of initial masses is still uncertain. Direct imaging of progenitors in pre-explosion archival images suggests an upper initial mass cutoff of ∼18M⊙. However, this is in tension with previous studies in which progenitor masses inferred by light-curve modelling tend to favour high-mass solutions. Moreover, it has been argued that light-curve modelling alone cannot provide a unique solution for the progenitor and explosion properties of SNe II.Aims.We develop a robust method which helps us to constrain the physical parameters of SNe II by simultaneously fitting their bolometric light curve and the evolution of the photospheric velocity to hydrodynamical models using statistical inference techniques.Methods.We created pre-supernova red supergiant models using the stellar evolution code MESA, varying the initial progenitor mass. We then processed the explosion of these progenitors through hydrodynamical simulations, where we changed the explosion energy and the synthesised nickel mass together with its spatial distribution within the ejecta. We compared the results to observations using Markov chain Monte Carlo methods.Results.We apply this method to a well-studied set of SNe with an observed progenitor in pre-explosion images and compare with results in the literature. Progenitor mass constraints are found to be consistent between our results and those derived by pre-SN imaging and the analysis of late-time spectral modelling.Conclusions.We have developed a robust method to infer progenitor and explosion properties of SN II progenitors which is consistent with other methods in the literature. Our results show that hydrodynamical modelling can be used to accurately constrain the physical properties of SNe II. This study is the starting point for a further analysis of a large sample of hydrogen-rich SNe.