bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meridional Gulf Stream Shifts Can Influence Wintertime Variability in the North Atlantic Storm Track and Greenland Blocking
Authors: Joyce Terrence M. , Kwon Young‐Oh , Seo Hyodae , Ummenhofer Caroline C. 
Published: January 2019

AbstractAfter leaving the U.S. East Coast, the northward flowing Gulf Stream (GS) becomes a zonal jet and carries along its frontal characteristics of strong flow and sea surface temperature gradients into the North Atlantic at midlatitudes. The separation location where it leaves the coast is also an anchor point for the wintertime synoptic storm track across North America to continue to develop and head across the ocean. We examine the meridional variability of the separated GS path on interannual to decadal time scales as an agent for similar changes in the storm track and blocking variability at midtroposphere from 1979 to 2012. We find that periods of northerly (southerly) GS path are associated with increased (suppressed) excursions of the synoptic storm track to the northeast over the Labrador Sea and reduced (enhanced) Greenland blocking. In both instances, GS shifts lead those in the midtroposphere by a few months.
Modeling the Quasi‐Trapped Electron Fluxes From Cosmic Ray Albedo Neutron Decay (CRAND)
Authors: Xiang Zheng , Li Xinlin , Selesnick R. , Temerin M. A. , Ni Binbin , Zhao Hong , Zhang Kun , Khoo Leng Ying 
Published: January 2019

AbstractRecently, cosmic ray albedo neutron decay (CRAND) has been identified as the main source of relativistic electrons measured at the inner edge of inner radiation belt. Here we introduce a drift‐source model that includes azimuthal drift and a CRAND electron source to simulate the quasi‐trapped electron distribution measured by the DEMETER satellite during 20–30 April 2010. The simulated longitude distribution of quasi‐trapped electron fluxes at the inner edge of inner radiation belt successfully reproduces the DEMETER observations, confirming CRAND as the main source for these electrons. Furthermore, a comparison of the energy spectrum and the L distribution of the quasi‐trapped relativistic electrons between simulations and observations further suggests that CRAND is likely the dominant source for 300–700‐keV quasi‐trapped electrons at L < 2 and L ≈ 3.
Cosmogenic Isotopes Unravel the Hydrochronology and Water Storage Dynamics of the Southern Sierra Critical Zone
Authors: Visser A. , Thaw M. , Deinhart A. , Bibby R. , Safeeq M. , Conklin M. , Esser B. , Van der Velde Y. 
Published: January 2019

AbstractOne of the principal questions in hydrology is how and when water leaves the critical zone storage as either stream flow or evapotranspiration. We investigated subsurface water storage and storage selection of the Southern Sierra Critical Zone Observatory (California, USA) within the age‐ranked storage selection framework, constrained by a novel combination of cosmogenic radioactive and stable isotopes: tritium, sodium‐22, sulfur‐35, and oxygen‐18. We found a significant positive correlation between tritium and stream flow rate and between sulfur‐35 and stream flow rate, indicating that the age distribution of stream flow varies with stream flow rate. Storage selection functions that vary with stream flow rate are better able to reproduce tritium concentrations in stream flow than functions that are constant in time. For the Southern Sierra Critical Zone, there is a strong preference to discharge the oldest water in storage during dry conditions but only a weak preference for younger water during wet conditions. The preference of evapotranspiration for younger water, constrained by oxygen‐18 in stream water, is essential to parameterize subsurface storage but needs to be confirmed by isotopic or other investigations of evapotranspiration. This is the first study to illustrate how a combination of cosmogenic radioactive isotopes reveals the hydrochronology and water storage dynamics of catchments, constrains the subsurface architecture of the critical zone, and provides insight into landscape evolution.
Downregulation of G2/mitotic-specific cyclinB1 triggers autophagy via AMPK-ULK1-dependent signal pathway in nasopharyngeal carcinoma cells
Authors: Xie Xianhe , Lin Wanzun , Zheng Weili , Chen Ting , Yang Haitao , Sun Lijun , Huang Fei , Wang Zili , Lin Heng , Chen Long , Liu Jun , Yang Liyan 
Published: January 2019

AbstractCyclinB1 is a regulatory protein involved in mitosis. Multiple lines of evidence indicate that cyclinB1 depletion constrains proliferation and induces apoptosis in human tumor cells. The cells become susceptible to suffer a critical situation when cyclinB1 is downregulated. Autophagy is a major intracellular degradation system that recycles nutrients, removes damaged organelles, and promotes cell survival under stressful conditions, whereas the role of autophagy in cyclinB1-deprived neoplastic cell as well as the underlying molecular mechanism remains obscure. Here we pioneeringly elaborated that specific knockdown of cyclinB1 triggered autophagy via AMPK-ULK1-dependent signal pathway through the elevation of ROS, rather than ATP in the cell lines of CNE-1 and CNE-2. Moreover, ROS scavengers demonstrated that the observed effect of cyclinB1 silencing on AMPK phosphorylation was ROS dependent. Additionally, double knockdown of AMPK and cyclinB1 evidently abrogated cyclinB1 silencing-induced autophagy. Summarily, this study first revealed that downregulation of cyclinB1 induced autophagy via AMPK-ULK1-dependent signal pathway, which represents a key step toward unveiling the mechanism how cell cycle checkpoint proteins regulate autophagy.
Gauge ambiguities imply Jaynes-Cummings physics remains valid in ultrastrong coupling QED
Authors: Stokes Adam , Nazir Ahsan 
Published: January 2019

AbstractUltrastrong-coupling between two-level systems and radiation is important for both fundamental and applied quantum electrodynamics (QED). Such regimes are identified by the breakdown of the rotating-wave approximation, which applied to the quantum Rabi model (QRM) yields the apparently less fundamental Jaynes-Cummings model (JCM). We show that when truncating the material system to two levels, each gauge gives a different description whose predictions vary significantly for ultrastrong-coupling. QRMs are obtained through specific gauge choices, but so too is a JCM without needing the rotating-wave approximation. Analysing a circuit QED setup, we find that this JCM provides more accurate predictions than the QRM for the ground state, and often for the first excited state as well. Thus, Jaynes-Cummings physics is not restricted to light-matter coupling below the ultrastrong limit. Among the many implications is that the system’s ground state is not necessarily highly entangled, which is usually considered a hallmark of ultrastrong-coupling.
The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells
Authors: Perucha Esperanza , Melchiotti Rossella , Bibby Jack A , Wu Wing , Frederiksen Klaus Stensgaard , Roberts Ceri A. , Hall Zoe , LeFriec Gaelle , Robertson Kevin A. , Lavender Paul , Gerwien Jens Gammeltoft , Taams Leonie S. , Griffin Julian L. , de Rinaldis Emanuele , van Baarsen Lisa G. M. , Kemper Claudia , Ghazal Peter , Cope Andrew P. 
Published: January 2019

AbstractThe mechanisms controlling CD4+ T cell switching from an effector to an anti-inflammatory (IL-10+) phenotype play an important role in the persistence of chronic inflammatory diseases. Here, we identify the cholesterol biosynthesis pathway as a key regulator of this process. Pathway analysis of cultured cytokine-producing human T cells reveals a significant association between IL-10 and cholesterol metabolism gene expression. Inhibition of the cholesterol biosynthesis pathway with atorvastatin or 25-hydroxycholesterol during switching from IFNγ+ to IL-10+ shows a specific block in immune resolution, defined as a significant decrease in IL-10 expression. Mechanistically, the master transcriptional regulator of IL10 in T cells, c-Maf, is significantly decreased by physiological levels of 25-hydroxycholesterol. Strikingly, progression to rheumatoid arthritis is associated with altered expression of cholesterol biosynthesis genes in synovial biopsies of predisposed individuals. Our data reveal a link between sterol metabolism and the regulation of the anti-inflammatory response in human CD4+ T cells.
Dual RNA-seq identifies human mucosal immunity protein Mucin-13 as a hallmark of Plasmodium exoerythrocytic infection
Authors: LaMonte Gregory M. , Orjuela-Sanchez Pamela , Calla Jaeson , Wang Lawrence T. , Li Shangzhong , Swann Justine , Cowell Annie N. , Zou Bing Yu , Abdel-Haleem Mohamed Alyaa M. , Villa Galarce Zaira Hellen , Moreno Marta , Tong Rios Carlos , Vinetz Joseph M. , Lewis Nathan , Winzeler Elizabeth A. 
Published: January 2019

AbstractThe exoerythrocytic stage of Plasmodium infection is a critical window for prophylactic intervention. Using genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we show that the human mucosal immunity gene, mucin-13 (MUC13), is strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm MUC13 transcript increases in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, marking both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes. This data provides insights into host-parasite interactions in Plasmodium infection, and demonstrates that a component of host mucosal immunity is reprogrammed during the progression of infection.
Mitotic chromosome binding predicts transcription factor properties in interphase
Authors: Raccaud Mahé , Friman Elias T. , Alber Andrea B. , Agarwal Harsha , Deluz Cédric , Kuhn Timo , Gebhardt J. Christof M. , Suter David M. 
Published: January 2019

AbstractMammalian transcription factors (TFs) differ broadly in their nuclear mobility and sequence-specific/non-specific DNA binding. How these properties affect their ability to occupy specific genomic sites and modify the epigenetic landscape is unclear. The association of TFs with mitotic chromosomes observed by fluorescence microscopy is largely mediated by non-specific DNA interactions and differs broadly between TFs. Here we combine quantitative measurements of mitotic chromosome binding (MCB) of 501 TFs, TF mobility measurements by fluorescence recovery after photobleaching, single molecule imaging of DNA binding, and mapping of TF binding and chromatin accessibility. TFs associating to mitotic chromosomes are enriched in DNA-rich compartments in interphase and display slower mobility in interphase and mitosis. Remarkably, MCB correlates with relative TF on-rates and genome-wide specific site occupancy, but not with TF residence times. This suggests that non-specific DNA binding properties of TFs regulate their search efficiency and occupancy of specific genomic sites.
In-situ high-speed X-ray imaging of piezo-driven directed energy deposition additive manufacturing
Authors: Wolff Sarah J. , Wu Hao , Parab Niranjan , Zhao Cang , Ehmann Kornel F. , Sun Tao , Cao Jian 
Published: January 2019

AbstractPowder-blown laser additive manufacturing adds flexibility, in terms of locally varying powder materials, to the ability of building components with complex geometry. Although the process is promising, porosity is common in a built component, hence decreasing fatigue life and mechanical strength. The understanding of the physical phenomena during the interaction of a laser beam and powder-blown deposition is limited and requires in-situ monitoring to capture the influences of process parameters on powder flow, absorptivity of laser energy into the substrate, melt pool dynamics and porosity formation. This study introduces a piezo-driven powder deposition system that allows for imaging of individual powder particles that flow into a scanning melt pool. Here, in-situ high-speed X-ray imaging of the powder-blown additive manufacturing process of Ti-6Al-4V powder particles is the first of its kind and reveals how laser-matter interaction influences powder flow and porosity formation.
On the causes of Arctic sea ice in the warm Early Pliocene
Authors: Clotten Caroline , Stein Ruediger , Fahl Kirsten , Schreck Michael , Risebrobakken Bjørg , De Schepper Stijn 
Published: January 2019

AbstractScattered and indirect evidence suggests that sea ice occurred as far south as the Iceland Sea during the Early Pliocene, when the global climate was warmer than present. However, conclusive evidence as well as potential mechanisms governing sea ice occurrence outside the Arctic Ocean during a time with elevated greenhouse gas concentrations are still elusive. Here we present a suite of organic biomarkers and palynological records from the Iceland Sea and Yermak Plateau. We show that sea ice appeared as early as ~4.5 Ma in the Iceland Sea. The sea ice either occurred seasonally or was transported southward with the East Greenland Current. The Yermak Plateau mostly remained free of sea ice and was influenced dominantly by Atlantic water. From ~4.0 Ma, occurrence of extended sea ice conditions at both the Yermak Plateau and Iceland Sea document a substantial expansion of sea ice in the Arctic. The expansion occurred contemporaneous with increased northward heat and moisture transport in the North Atlantic region, which likely led to a fresher Arctic Ocean that favors sea ice formation. This extensive sea ice cover along the pathway of the East Greenland Current gradually isolated Greenland from warmer Atlantic water in the Late Pliocene, providing a positive feedback for ice sheet expansion in Greenland.
Flax latitudinal adaptation at LuTFL1 altered architecture and promoted fiber production
Authors: Gutaker Rafal M. , Zaidem Maricris , Fu Yong-Bi , Diederichsen Axel , Smith Oliver , Ware Roselyn , Allaby Robin G. 
Published: January 2019

AbstractAfter domestication in the Near East around 10,000 years ago several founder crops, flax included, spread to European latitudes. On reaching northerly latitudes the architecture of domesticated flax became more suitable to fiber production over oil, with longer stems, smaller seeds and fewer axillary branches. Latitudinal adaptations in crops typically result in changes in flowering time, often involving the PEBP family of genes that also have the potential to influence plant architecture. Two PEBP family genes in the flax genome,LuTFL1andLuTFL2, vary in wild and cultivated flax over latitudinal range with cultivated flax receivingLuTFL1alleles from northerly wild flax populations. Compared to a background of population structure of flaxes over latitude, theLuTFL1alleles display a level of differentiation that is consistent with selection for an allele III in the north. We demonstrate through heterologous expression inArabidopsis thalianathatLuTFL1is a functional homolog ofTFL1inA.thalianacapable of changing both flowering time and plant architecture. We conclude that specialized fiber flax types could have formed as a consequence of a natural adaptation of cultivated flax to higher latitudes.
Quantitative monitoring of the cytoplasmic release of NCp7 proteins from individual HIV-1 viral cores during the early steps of infection
Authors: Zgheib Sarwat , Lysova Iryna , Réal Eleonore , Dukhno Oleksii , Vauchelles Romain , Pires Manuel , Anton Halina , Mély Yves 
Published: January 2019

AbstractFluorescence microscopy imaging of individual HIV-1 viruses necessitates a specific labeling of viral structures that minimally perturbs the infection process. Herein, we used HIV-1 pseudoviruses containing NCp7 fused to a tetracystein (TC) tag, labeled by a biarsenical fluorescein derivative (FlAsH) to quantitatively monitor the NCp7 protein concentration in the viral cores during the early stages of infection. Single particle imaging of individual pseudoviruses with defined ratios of TC-tagged to non tagged NCp7 proteins, together with theoretical modeling of energy transfer between FlAsH dyes, showed that the high packaging of TC-tagged proteins in the viral cores causes a strong fluorescence quenching of FlAsH and that the fluorescence intensity of individual viral complexes is an appropriate parameter to monitor changes in the amount of NCp7 molecules within the viral particles during infection. Interestingly, we observed a dramatic fluorescence increase of individual FlAsH-labeled pseudoviruses containing 100% TC-tagged NCp7 proteins in infected cells at 8 and 16 h post-infection. This effect was significantly lower for pseudoviruses expressing TC-tagged integrase. Therefore, this fluorescence increase is likely related to the cytoplasmic viral transformation and the release of NCp7 molecules from the viral complexes. This loss of quenching effect is largely reduced when reverse transcriptase is inhibited, showing that NCp7 release is connected to viral DNA synthesis. A spatial analysis further revealed that NCp7-TC release is more pronounced in the perinuclear space, where capsid disassembly is thought to be completed. Quantification of NCp7-TC content based on fluorescence quenching presented in this study evidences for the first time the cytoplasmic release of NCp7 during the remodeling of HIV-1 viral particles on their journey toward the nucleus. The developed approach can be applied to quantify dye concentrations in a wide range of nano-objects by fluorescence microscopy techniques.
USP19 deubiquitinates EWS-FLI1 to regulate Ewing sarcoma growth
Authors: Gierisch Maria E. , Pedot Gloria , Walser Franziska , Lopez-Garcia Laura A. , Jaaks Patricia , Niggli Felix K. , Schäfer Beat W. 
Published: January 2019

AbstractEwing sarcoma is the second most common pediatric bone and soft tissue tumor presenting with an aggressive behavior and prevalence to metastasize. The diagnostic translocation t(22;11)(q24;12) leads to expression of the chimeric oncoprotein EWS-FLI1 which is uniquely expressed in all tumor cells and maintains their survival. Constant EWS-FLI1 protein turnover is regulated by the ubiquitin proteasome system. Here, we now identified ubiquitin specific protease 19 (USP19) as a regulator of EWS-FLI1 stability using an siRNA based screening approach. Depletion of USP19 resulted in diminished EWS-FLI1 protein levels and, vice versa, upregulation of active USP19 stabilized the fusion protein. Importantly, stabilization appears to be specific for the fusion protein as it could not be observed neither for EWSR1 nor for FLI1 wild type proteins even though USP19 binds to the N-terminal EWS region to regulate deubiquitination of both EWS-FLI1 and EWSR1. Further, stable shUSP19 depletion resulted in decreased cell growth and diminished colony forming capacity in vitro, and significantly delayed tumor growth in vivo. Our findings not only provide novel insights into the importance of the N-terminal EWSR1 domain for regulation of fusion protein stability, but also indicate that inhibition of deubiquitinating enzyme(s) might constitute a novel therapeutic strategy in treatment of Ewing sarcoma.
Network Analysis Reveals TNF as a Major Hub of Reactive Inflammation Following Spinal Cord Injury
Authors: Zhu Weiping , Chen Xuning , Ning Le , Jin Kan 
Published: January 2019

AbstractSpinal cord injury (SCI) leads to reactive inflammation and other harmful events that limit spinal cord regeneration. We propose an approach for studying the mechanisms at the levels of network topology, gene ontology, signaling pathways, and disease inference. We treated inflammatory mediators as toxic chemicals and retrieved the genes and interacting proteins associated with them via a set of biological medical databases and software. We identified >10,000 genes associated with SCI. Tumor necrosis factor (TNF) had the highest scores, and the top 30 were adopted as core data. In the core interacting protein network, TNF and other top 10 nodes were the major hubs. The core members were involved in cellular responses and metabolic processes, as components of the extracellular space and regions, in protein-binding and receptor-binding functions, as well as in the TNF signaling pathway. In addition, both seizures and SCI were highly associated with TNF levels; therefore, for achieving a better curative effect on SCI, TNF and other major hubs should be targeted together according to the theory of network intervention, rather than a single target such as TNF alone. Furthermore, certain drugs used to treat epilepsy could be used to treat SCI as adjuvants.
Depletion of B cell-activating factor attenuates hepatic fat accumulation in a murine model of nonalcoholic fatty liver disease
Authors: Nakamura Yoshiko , Abe Masanori , Kawasaki Keitarou , Miyake Teruki , Watanabe Takao , Yoshida Osamu , Hirooka Masashi , Matsuura Bunzo , Hiasa Yoichi 
Published: January 2019

AbstractObesity-induced adipose-tissue dysfunction is a critical contributor to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). B cell-activating factor (BAFF) is an adipokine related to impaired insulin sensitivity, and the serum BAFF concentration is associated with NAFLD severity. In this study, we aimed to determine the direct in vivo role of BAFF in the development of insulin resistance, adipocyte dysfunction, and hepatic steatosis using BAFF−/− mice fed a high-fat diet (HFD). HFD-fed BAFF−/− mice exhibited significantly improved insulin sensitivity despite their increased weight gain and adiposity relative to HFD-fed wild-type mice. Moreover, inflammation, especially the accumulation of CD11c+ adipose-tissue macrophages, and fibrosis of epididymal adipose tissue were reduced, contributing to healthy adipose-tissue expansion in obese BAFF−/− mice. In line with metabolically healthy obesity, hepatic steatosis also decreased, and we observed attenuated de novo lipogenesis in both the livers and hepatocytes of BAFF−/− mice. Our data revealed that BAFF serves as a potential stimulator of unhealthy adipose-tissue expansion by triggering inflammation and fibrosis and ultimately leading to enhanced insulin resistance and NAFLD. Therefore, these results suggest that BAFF is a promising target for diabetes and NAFLD treatment.
Mitochondrial Dysfunction in Aged Macrophages and Lung during Primary Streptococcus pneumoniae Infection is Improved with Pirfenidone
Authors: Plataki Maria , Cho Soo Jung , Harris Rebecca M. , Huang Hua-Rong , Yun Ha Seon , Schiffer Kristen T. , Stout-Delgado Heather W. 
Published: January 2019

AbstractPneumococcal infections remain a leading cause of death in older adults, with the most serious cases occurring in persons ≥65 years of age. There is an urgent need to investigate molecular pathways underlying these impairments and devise new therapeutics to modulate innate immunity. The goal of our current study is to understand the impact of chronological aging on mitochondrial function in response to Streptococcus pneumoniae, a causative agent of bacterial pneumonia. Using chronologically aged murine models, our findings demonstrate that decreased ATP production is associated with dysregulated mitochondrial complex expression, enhanced oxidative stress, diminished antioxidant responses, and decreased numbers of healthy mitochondria in aged adult macrophages and lung in response to S. pneumoniae. Pre-treatment of aged macrophages with pirfenidone, an anti-fibrotic drug with antioxidant and anti-inflammatory properties, improved mitochondrial function and decreased cellular oxidative stress responses. In vivo administration of pirfenidone decreased superoxide formation, increased healthy mitochondria number, improved ATP production, and decreased inflammatory cell recruitment and pulmonary oedema in aged mouse lung during infection. Taken together, our data shed light on the susceptibility of older persons to S. pneumoniae and provide a possible therapeutic to improve mitochondrial responses in this population.