bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation and Intensification of Mesoscale Anticyclones by Orographic Wind Jets: The Case of Ierapetra Eddies Forced by the Etesians
Authors: Ioannou Artemis , Stegner Alexandre , Dubos Thomas , Le Vu Briac , Speich Sabrina 
Published: June 2020

AbstractMotivated by the recurrent formation and intensification of the Ierapetra anticyclones in the southeast of Crete, we investigated with a reduced gravity model the response of the oceanic surface layer to a seasonal wind jet that varies slowly (over several weeks or months) and mimics the Etesian winds. Our study answers why the oceanic response to such forcing is mainly a large and intense anticyclone. We build a dimensionless parameter that integrates in time the Ekman pumping and quantifies the relative amplitude of the isopycnal displacement induced by the local wind stress curl. According to the range of the wind forcing parameter, the oceanic response to a symmetric wind jet could be a symmetric dipole or a strongly asymmetric structure dominated by an intense and robust anticyclone. This intrinsic asymmetry is driven by the finite isopycnal displacements that occur when the wind forcing parameter reaches unity. Since the anticyclonic wind shear for the Etesian wind jet is 2 times larger than the cyclonic one, the asymmetry of the oceanic response is enhanced. Several weeks after the wind forcing has stopped, an intense mesoscale anticyclone which satisfies the cyclogeostrophic balance remains. Moreover, if a similar wind jet blows on a preexisting anticyclone, the latter remains robust and coherent and gets reintensified in agreement with the previous analysis of remote sensing observations. Hence, this paper is the first numerical study which provides a dynamical understanding for the formation of the single Ierapetra anticyclones and explains their intensification 1 year after formation.
Dynamics of Auroral Precipitation Boundaries Associated With STEVE and SAID
Authors: Nishimura Y. , Donovan E. F. , Angelopoulos V. , Nishitani N. 
Published: June 2020

AbstractUsing Defense Meteorological Satellite Program (DMSP) and National Oceanic and Atmospheric Administration (NOAA) satellite observations and ground‐based observations by the THEMIS all‐sky imagers (ASIs) and SuperDARN radars, we determine how the equatorward boundary locations of ring current ions and plasma sheet electrons at pre‐midnight relate to occurrence of strong thermal emission velocity enhancement (STEVE) and intense subauroral ion drifts (SAID) during substorms. We found that the STEVE events are associated with a sharper gradient of electron precipitating flux, lower precipitating ion flux, and a narrower (<1°) latitudinal gap between the equatorward boundaries of trapped ring current ions and precipitating plasma sheet electrons and narrower region‐2 field‐aligned currents (FACs) than for the non‐STEVE events. The narrow gap of the particle boundaries contains intense SAID, higher upflow velocity, lower trough density, and slightly higher electron temperature than those for the non‐STEVE events. The non‐STEVE substorms have much wider gaps between the trapped ions and precipitating electrons, and subauroral polarization streams (SAPS) do not show intense SAID. These results indicate that subauroral flows and downward FACs for the STEVE events can only flow within the latitudinally narrow subauroral low‐conductance region between the ion and electron boundaries, resulting in intense SAID and heating. During the non‐STEVE events, the SAPS flows can flow in the latitudinally wide region without forming intense SAID.
Viscoelastic Relaxation within the Moon and the Phase Lead of Its Cassini State
Authors: Organowski Olivier , Dumberry Mathieu 
Published: June 2020

AbstractAnalyses of Lunar Laser Ranging data show that the spin symmetry axis of the Moon is ahead of its expected Cassini state by an angle of ϕp = 0.27 arcsec. This indicates the presence of one or more dissipation mechanisms acting on the lunar rotation. A combination of solid‐body tides and viscous core‐mantle coupling have been proposed in previous studies. Here, we investigate whether viscoelastic deformation within a solid inner core at the center of the Moon can also account for a part of the observed phase lead angle ϕp. We build a rotational dynamic model of the Cassini state of the Moon that comprises an inner core, a fluid core, and a mantle and where solid regions are allowed to deform viscoelastically in response to an applied forcing. We show that the presence of an inner core does not change the global monthly Q of the Moon and, hence, that the contribution from solid‐body tides to ϕp is largely unaffected by an inner core. However, we also show that viscoelastic deformation within the inner core, acting to realign its figure axis with that of the mantle, can contribute significantly to ϕp through inner core‐mantle gravitational coupling. We show that the contribution to ϕp is largest when the inner core viscosity is in the range of 1013 to 1014 Pa s, when the inner core radius is large and when the free inner core nutation frequency approaches a resonance with the precession frequency of 2π/18.6 yr−1.
ETo‐Brazil: A Daily Gridded Reference Evapotranspiration Data Set for Brazil (2000–2018)
Authors: Althoff Daniel , Dias Santos Henrique Brant , Filgueiras Roberto , Rodrigues Lineu Neiva 
Published: June 2020

AbstractThe reference evapotranspiration (ETo) has long been used as a climate parameter for many studies in climatology and hydrology. However, many regions suffer from shortage of both meteorological monitoring stations and historical information on ETo. Thus, the objective of this study was to develop a daily gridded reference evapotranspiration data set for Brazil that matches the period and grid cells of the Global Precipitation Measurement (GPM) data. ETo was calculated using data from 849 weather stations over the period from 1 June 2000 to 31 December 2018. The features used to model ETo were the GPM daily data set, WorldClim averages monthly, and two engineered features. Among the machine learning algorithms assessed, the Cubist presented the best performance‐computation cost trade‐off in a subset of the entire data and, therefore, was selected to model ETo daily. The developed data set presented root mean square error of 0.65 mm day−1, or 16% lower than previous ETo data set developed for Brazil using interpolation techniques. The GPM and engineered features showed higher importance for the models trained during the wet season, while the WorldClim maximum temperature averages monthly were more important during the dry and cold season. The new gridded reference evapotranspiration data set for Brazil (ETo‐Brazil) was made freely available to the community.
Identification of a novel polymorphism associated with reduced clozapine concentration in schizophrenia patients—a genome-wide association study adjusting for smoking habits
Authors: Smith Robert Løvsletten , O’Connell Kevin , Athanasiu Lavinia , Djurovic Srdjan , Kringen Marianne Kristiansen , Andreassen Ole A. , Molden Espen 
Published: June 2020

AbstractClozapine (CLZ) is the superior antipsychotic drug for treatment of schizophrenia, but exhibits an extensive interpatient pharmacokinetic variability. Here, we conducted a genome-wide association study (GWAS) of CLZ serum concentration adjusting for known smoking habits, which is a major nongenetic factor reducing CLZ levels. The study included 484 patients with 10,283 steady-state serum concentrations of CLZ and N-desmethylclozapine, prescribed dosing, co-medications and known smoking habits (n = 422; 9284 serum samples) from a therapeutic drug monitoring (TDM) service. The GWAS analyses were performed with and without smoking habits as covariate, where possible hits were assessed in relation to the target CLZ concentration range applied in the TDM service (300–2500 nmol/L). The smoking-independent analysis of N-desmethylclozapine serum concentration and the CLZ-to-N-desmethylclozapine ratio replicated the previously identified locus on chromosome 4. After adjusting for smoking habits in patients confirmed as ‘smokers’ (61%) or ‘nonsmokers’ (39%), a novel variant (rs28379954; minor T>C allele frequency 4.1%; 7.6% CT carriers in the population) within the gene encoding the nuclear factor 1 B-type (NFIB) was significantly associated with reduced CLZ serum concentration (p = 1.68 × 10−8, beta = −0.376; explained variance 7.63%). There was no significant association between rs28379954 and N-desmethylclozapine concentration in the GWAS analysis (p = 5.63 × 10−5). The fraction of CLZ TDM samples below 300 nmol/L was significantly higher in carriers vs. noncarriers of the rs28379954 minor C allele [12.0% (95% CI: 9.4–14.7) vs. 6.2% (95% CI: 5.7–6.8), p < 0.001]. We identified a novel variant in the NFIB gene associated with reduced CLZ levels and increased risk of subtherapeutic serum concentrations. This warrants testing of clinical relevance of screening for this gene variant, and also experimental studies to investigate the biological mechanisms of NFIB involvement in CLZ pharmacokinetics.
Genomic analysis of primary plasma cell leukemia reveals complex structural alterations and high-risk mutational patterns
Authors: Schinke Carolina , Boyle Eileen M. , Ashby Cody , Wang Yan , Lyzogubov Valeriy , Wardell Christopher , Qu Pingping , Hoering Antje , Deshpande Shayu , Ryan Katie , Thanendrarajan Sharmilan , Mohan Meera , Yarlagadda Naveen , Khan Maliha , Choudhury Samrat Roy , Zangari Maurizio , van Rhee Frits , Davies Faith , Barlogie Bart , Morgan Gareth , Walker Brian A. 
Published: June 2020

AbstractPrimary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) that is characterized by the presence of ≥20% circulating plasma cells. Overall survival remains poor despite advances of anti-MM therapy. The disease biology as well as molecular mechanisms that distinguish pPCL from non-pPCL MM remain poorly understood and, given the rarity of the disease, are challenging to study. In an attempt to identify key biological mechanisms that result in the aggressive pPCL phenotype, we performed whole-exome sequencing and gene expression analysis in 23 and 41 patients with newly diagnosed pPCL, respectively. The results reveal an enrichment of complex structural changes and high-risk mutational patterns in pPCL that explain, at least in part, the aggressive nature of the disease. In particular, pPCL patients with traditional low-risk features such as translocation t(11;14) or hyperdiploidy accumulated adverse risk genetic events that could account for the poor outcome in this group. Furthermore, gene expression profiling showed upregulation of adverse risk modifiers in pPCL compared to non-pPCL MM, while adhesion molecules and extracellular matrix proteins became increasingly downregulated. In conclusion, this is one of the largest studies to dissect pPCL on a genomic and molecular level.
The lncRNA RP11-142A22.4 promotes adipogenesis by sponging miR-587 to modulate Wnt5β expression
Authors: Zhang Tongtong , Liu Hongtao , Mao Rui , Yang Huawu , Zhang Yuanchuan , Zhang Yu , Guo Pengsen , Zhan Dafang , Xiang Bin , Liu Yanjun 
Published: June 2020

AbstractEmerging evidence suggests that long noncoding RNAs (lncRNAs) play essential roles in the regulation of gene expression. However, the functional contributions of lncRNAs to adipogenesis remain largely unexplored. In this study, we investigated global changes in the expression patterns of lncRNAs in visceral adipose tissue and identified RP11-142A22.4 as a significantly upregulated lncRNA. In isolated preadipocytes, knockdown of RP11-142A22.4 inhibited differentiation and reduced C/EBP-α and PPAR-γ expression. Investigations of the underlying mechanisms revealed that RP11-142A22.4 contains a functional miR-587 binding site. Mutation of the binding sites for RP11-142A22.4 in miR-587 abolished the interaction, as indicated by a luciferase reporter assay. Furthermore, RP11-142A22.4 affected the expression of miR-587 and its target gene Wnt5β. Overexpression of miR-587 blocked the inhibitory effect of RP11-142A22.4 on preadipocyte differentiation. Moreover, the downregulation of miR-587 restored preadipocyte differentiation upon inhibition by RP11-142A22.4 silencing. Our results suggest that RP11-142A22.4 can control adipocyte differentiation via the miR-587/Wnt5β signaling pathway and serve as a potential target for obesity treatments.
The role of MDM2–p53 axis dysfunction in the hepatocellular carcinoma transformation
Authors: Cao Hui , Chen Xiaosong , Wang Zhijun , Wang Lei , Xia Qiang , Zhang Wei 
Published: June 2020

AbstractLiver cancer is the second most frequent cause of cancer-related death globally. The main histological subtype is hepatocellular carcinoma (HCC), which is derived from hepatocytes. According to the epidemiologic studies, the most important risk factors of HCC are chronic viral infections (HBV, HCV, and HIV) and metabolic disease (metabolic syndrome). Interestingly, these carcinogenic factors that contributed to HCC are associated with MDM2–p53 axis dysfunction, which presented with inactivation of p53 and overactivation of MDM2 (a transcriptional target and negative regulator of p53). Mechanically, the homeostasis of MDM2–p53 feedback loop plays an important role in controlling the initiation and progression of HCC, which has been found to be dysregulated in HCC tissues. To maintain long-term survival in hepatocytes, hepatitis viruses have lots of ways to destroy the defense strategies of hepatocytes by inducing TP53 mutation and silencing, promoting MDM2 overexpression, accelerating p53 degradation, and stabilizing MDM2. As a result, genetic instability, chronic ER stress, oxidative stress, energy metabolism switch, and abnormalities in antitumor genes can be induced, all of which might promote hepatocytes’ transformation into hepatoma cells. In addition, abnormal proliferative hepatocytes and precancerous cells cannot be killed, because of hepatitis viruses-mediated exhaustion of Kupffer cells and hepatic stellate cells (HSCs) and CD4+T cells by disrupting their MDM2–p53 axis. Moreover, inefficiency of hepatic immune response can be further aggravated when hepatitis viruses co-infected with HIV. Unlike with chronic viral infections, MDM2–p53 axis might play a dual role in glucolipid metabolism of hepatocytes, which presented with enhancing glucolipid catabolism, but promoting hepatocyte injury at the early and late stages of glucolipid metabolism disorder. Oxidative stress, fatty degeneration, and abnormal cell growth can be detected in hepatocytes that were suffering from glucolipid metabolism disorder, and all of which could contribute to HCC initiation. In this review, we focus on the current studies of the MDM2–p53 axis in HCC, and specifically discuss the impact of MDM2–p53 axis dysfunction by viral infection and metabolic disease in the transformation of normal hepatocytes into hepatoma cells. We also discuss the therapeutic avenues and potential targets that are being developed to normalize the MDM2–p53 axis in HCC.
Evaluation of CNV detection tools for NGS panel data in genetic diagnostics
Authors: Moreno-Cabrera José Marcos , del Valle Jesús , Castellanos Elisabeth , Feliubadaló Lidia , Pineda Marta , Brunet Joan , Serra Eduard , Capellà Gabriel , Lázaro Conxi , Gel Bernat 
Published: June 2020

AbstractAlthough germline copy-number variants (CNVs) are the genetic cause of multiple hereditary diseases, detecting them from targeted next-generation sequencing data (NGS) remains a challenge. Existing tools perform well for large CNVs but struggle with single and multi-exon alterations. The aim of this work is to evaluate CNV calling tools working on gene panel NGS data and their suitability as a screening step before orthogonal confirmation in genetic diagnostics strategies. Five tools (DECoN, CoNVaDING, panelcn.MOPS, ExomeDepth, and CODEX2) were tested against four genetic diagnostics datasets (two in-house and two external) for a total of 495 samples with 231 single and multi-exon validated CNVs. The evaluation was performed using the default and sensitivity-optimized parameters. Results showed that most tools were highly sensitive and specific, but the performance was dataset dependant. When evaluating them in our diagnostics scenario, DECoN and panelcn.MOPS detected all CNVs with the exception of one mosaic CNV missed by DECoN. However, DECoN outperformed panelcn.MOPS specificity achieving values greater than 0.90 when using the optimized parameters. In our in-house datasets, DECoN and panelcn.MOPS showed the highest performance for CNV screening before orthogonal confirmation. Benchmarking and optimization code is freely available at https://github.com/TranslationalBioinformaticsIGTP/CNVbenchmarkeR.
The atypical chemokine receptor ACKR3/CXCR7 is a broad-spectrum scavenger for opioid peptides
Authors: Meyrath Max , Szpakowska Martyna , Zeiner Julian , Massotte Laurent , Merz Myriam P. , Benkel Tobias , Simon Katharina , Ohnmacht Jochen , Turner Jonathan D. , Krüger Rejko , Seutin Vincent , Ollert Markus , Kostenis Evi , Chevigné Andy 
Published: June 2020

AbstractEndogenous opioid peptides and prescription opioid drugs modulate pain, anxiety and stress by activating opioid receptors, currently classified into four subtypes. Here we demonstrate that ACKR3/CXCR7, hitherto known as an atypical scavenger receptor for chemokines, is a broad-spectrum scavenger of opioid peptides. Phylogenetically, ACKR3 is intermediate between chemokine and opioid receptors and is present in various brain regions together with classical opioid receptors. Functionally, ACKR3 is a scavenger receptor for a wide variety of opioid peptides, especially enkephalins and dynorphins, reducing their availability for the classical opioid receptors. ACKR3 is not modulated by prescription opioids, but we show that an ACKR3-selective subnanomolar competitor peptide, LIH383, can restrain ACKR3’s negative regulatory function on opioid peptides in rat brain and potentiate their activity towards classical receptors, which may open alternative therapeutic avenues for opioid-related disorders. Altogether, our results reveal that ACKR3 is an atypical opioid receptor with cross-family ligand selectivity.
Distinct pseudokinase domain conformations underlie divergent activation mechanisms among vertebrate MLKL orthologues
Authors: Davies Katherine A. , Fitzgibbon Cheree , Young Samuel N. , Garnish Sarah E. , Yeung Wayland , Coursier Diane , Birkinshaw Richard W. , Sandow Jarrod J. , Lehmann Wil I. L. , Liang Lung-Yu , Lucet Isabelle S. , Chalmers James D. , Patrick Wayne M. , Kannan Natarajan , Petrie Emma J. , Czabotar Peter E. , Murphy James M. 
Published: June 2020

AbstractThe MLKL pseudokinase is the terminal effector in the necroptosis cell death pathway. Phosphorylation by its upstream regulator, RIPK3, triggers MLKL’s conversion from a dormant cytoplasmic protein into oligomers that translocate to, and permeabilize, the plasma membrane to kill cells. The precise mechanisms underlying these processes are incompletely understood, and were proposed to differ between mouse and human cells. Here, we examine the divergence of activation mechanisms among nine vertebrate MLKL orthologues, revealing remarkable specificity of mouse and human RIPK3 for MLKL orthologues. Pig MLKL can restore necroptotic signaling in human cells; while horse and pig, but not rat, MLKL can reconstitute the mouse pathway. This selectivity can be rationalized from the distinct conformations observed in the crystal structures of horse and rat MLKL pseudokinase domains. These studies identify important differences in necroptotic signaling between species, and suggest that, more broadly, divergent regulatory mechanisms may exist among orthologous pseudoenzymes.
Rapidly-migrating and internally-generated knickpoints can control submarine channel evolution
Authors: Heijnen Maarten S. , Clare Michael A. , Cartigny Matthieu J. B. , Talling Peter J. , Hage Sophie , Lintern D. Gwyn , Stacey Cooper , Parsons Daniel R. , Simmons Stephen M. , Chen Ye , Sumner Esther J. , Dix Justin K. , Hughes Clarke John E. 
Published: June 2020

AbstractSubmarine channels are the primary conduits for terrestrial sediment, organic carbon, and pollutant transport to the deep sea. Submarine channels are far more difficult to monitor than rivers, and thus less well understood. Here we present 9 years of time-lapse mapping of an active submarine channel along its full length in Bute Inlet, Canada. Past studies suggested that meander-bend migration, levee-deposition, or migration of (supercritical-flow) bedforms controls the evolution of submarine channels. We show for the first time how rapid (100–450 m/year) upstream migration of 5-to-30 m high knickpoints can control submarine channel evolution. Knickpoint migration-related changes include deep (>25 m) erosion, and lateral migration of the channel. Knickpoints in rivers are created by external factors, such as tectonics, or base-level change. However, the knickpoints in Bute Inlet appear internally generated. Similar knickpoints are found in several submarine channels worldwide, and are thus globally important for how channels operate.
Remote assessment of the fate of phytoplankton in the Southern Ocean sea-ice zone
Authors: Moreau Sébastien , Boyd Philip W. , Strutton Peter G. 
Published: June 2020

AbstractIn the Southern Ocean, large-scale phytoplankton blooms occur in open water and the sea-ice zone (SIZ). These blooms have a range of fates including physical advection, downward carbon export, or grazing. Here, we determine the magnitude, timing and spatial trends of the biogeochemical (export) and ecological (foodwebs) fates of phytoplankton, based on seven BGC-Argo floats spanning three years across the SIZ. We calculate loss terms using the production of chlorophyll—based on nitrate depletion—compared with measured chlorophyll. Export losses are estimated using conspicuous chlorophyll pulses at depth. By subtracting export losses, we calculate grazing-mediated losses. Herbivory accounts for ~90% of the annually-averaged losses (169 mg C m−2 d−1), and phytodetritus POC export comprises ~10%. Furthermore, export and grazing losses each exhibit distinctive seasonality captured by all floats spanning 60°S to 69°S. These similar trends reveal widespread patterns in phytoplankton fate throughout the Southern Ocean SIZ.
Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments
Authors: Henrichs Verena , Grycova Lenka , Barinka Cyril , Nahacka Zuzana , Neuzil Jiri , Diez Stefan , Rohlena Jakub , Braun Marcus , Lansky Zdenek 
Published: June 2020

AbstractIntracellular trafficking of organelles, driven by kinesin-1 stepping along microtubules, underpins essential cellular processes. In absence of other proteins on the microtubule surface, kinesin-1 performs micron-long runs. Under crowding conditions, however, kinesin-1 motility is drastically impeded. It is thus unclear how kinesin-1 acts as an efficient transporter in intracellular environments. Here, we demonstrate that TRAK1 (Milton), an adaptor protein essential for mitochondrial trafficking, activates kinesin-1 and increases robustness of kinesin-1 stepping on crowded microtubule surfaces. Interaction with TRAK1 i) facilitates kinesin-1 navigation around obstacles, ii) increases the probability of kinesin-1 passing through cohesive islands of tau and iii) increases the run length of kinesin-1 in cell lysate. We explain the enhanced motility by the observed direct interaction of TRAK1 with microtubules, providing an additional anchor for the kinesin-1-TRAK1 complex. Furthermore, TRAK1 enables mitochondrial transport in vitro. We propose adaptor-mediated tethering as a mechanism regulating kinesin-1 motility in various cellular environments.