bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal Characteristic of the Mesoscale Plasma Flow Perturbations in the High‐Latitude Ionosphere
Authors: Chen Yun‐Ju , Heelis Roderick A. 
Published: December 2018

AbstractSpatial and temporal characteristics of flow perturbations in the high‐latitude ionosphere are important considerations for energy deposition from the magnetosphere. In this study, we examine the temporal characteristics of plasma flow perturbations with spatial scales between 100 and 400 km from two consecutive Defense Meteorological Satellite Program (DMSP) passes that have about the same orbital plane and sample time spacing between a few seconds and 20 min during local summer seasons in 2007‐2015. The temporal characteristics of mesoscale flow perturbations are described by rise and saturation times for growth and decay derived from the changes in magnitude of perturbations and the time separation between consecutive samples. Observations suggest that the rise times for both growth and decay are shorter for small spatial scales (1–2 min, 100–200 km) and longer for large spatial scales (3–5 min, 200–400 km). The saturation time for decay is ~10 min for small scales and ~20 min for large scales. The growth saturation time is about 5–10 min for both scale sizes. These characteristic times for growth are always shorter than the decay times. If the difference in these characteristic times between growth and decay is produced by motion of a perturbation with the background flow through the observed volume, then a longitudinal scale size of 750 km or 1.5 hr of local time is implied.
Earthquake Nucleation Size: Evidence of Loading Rate Dependence in Laboratory Faults
Authors: Guérin‐Marthe Simon , Nielsen Stefan , Bird Robert , Giani Stefano , Di Toro Giulio 
Published: December 2018

AbstractRecent Global Positioning System observations of major earthquakes such as the 2014 Chile megathrust show a slow preslip phase releasing a significant portion of the total moment (Ruiz et al., 2014, https://doi.org/10.1126/science.1256074). Despite advances from theoretical stability analysis (Rubin & Ampuero, 2005, https://doi.org/10.1029/2005JB003686; Ruina, 1983, https://doi.org/10.1029/jb088ib12p10359) and modeling (Kaneko et al., 2017, https://doi.org/10.1002/2016GL071569), it is not fully understood what controls the prevalence and the amount of slip in the nucleation process. Here we present laboratory observations of slow slip preceding dynamic rupture, where we observe a dependence of nucleation size and position on the loading rate (laboratory equivalent of tectonic loading rate). The setup is composed of two polycarbonate plates under direct shear with a 30‐cm long slip interface. The results of our laboratory experiments are in agreement with the preslip model outlined by Ellsworth and Beroza (1995, https://doi.org/10.1126/science.268.5212.851) and observed in laboratory experiments (Latour et al., 2013, https://doi.org/10.1002/grl.50974; Nielsen et al., 2010, https://doi.org/10.1111/j.1365-246x.2009.04444.x; Ohnaka & Kuwahara, 1990, https://doi.org/10.1016/0040-1951(90)90138-X), which show a slow slip followed by an acceleration up to dynamic rupture velocity. However, further complexity arises from the effect of (1) rate of shear loading and (2) inhomogeneities on the fault surface. In particular, we show that when the loading rate is increased from 10−2 to 6 MPa/s, the nucleation length can shrink by a factor of 3, and the rupture nucleates consistently on higher shear stress areas. The nucleation lengths measured fall within the range of the theoretical limits Lb and
derived by Rubin and Ampuero (2005, https://doi.org/10.1029/2005JB003686) for rate‐and‐state friction laws.
Merging of Storm Time Midlatitude Traveling Ionospheric Disturbances and Equatorial Plasma Bubbles
Authors: Aa Ercha , Zou Shasha , Ridley Aaron , Zhang Shunrong , Coster Anthea J. , Erickson Philip J. , Liu Siqing , Ren Jiaen 
Published: December 2018

AbstractPostsunset midlatitude traveling ionospheric disturbances (TIDs) and equatorial plasma bubbles (EPBs) were simultaneously observed over American sector during the geomagnetic storm on 8 September 2017. The characteristics of TIDs are analyzed by using a combination of the Millstone Hill incoherent scatter radar data and 2‐D detrended total electron content (TEC) from ground‐based Global Navigation Satellite System receivers. The main results associated with EPBs are as follows: (1) stream‐like structures of TEC depletion occurred simultaneously at geomagnetically conjugate points, (2) poleward extension of the TEC irregularities/depletions along the magnetic field lines, (3) severe equatorial and midlatitude electron density (Ne) bite outs observed by Defense Meteorological Satellite Program and Swarm satellites, and (4) enhancements of ionosphere F layer virtual height and vertical drifts observed by equatorial ionosondes near the EPBs initiation region. The stream‐like TEC depletions reached 46° magnetic latitudes that map to an apex altitude of 6,800 km over the magnetic equator using International Geomagnetic Reference Field. The formation of this extended density depletion structure is suggested to be due to the merging between the altitudinal/latitudinal extension of EPBs driven by strong prompt penetration electric field and midlatitude TIDs. Moreover, the poleward portion of the depletion/irregularity drifted westward and reached the equatorward boundary of the ionospheric main trough. This westward drift occurred at the same time as the sudden expansion of the convection pattern and could be attributed to the strong returning westward flow near the subauroral polarization stream region. Other possible mechanisms for the westward tilt are also discussed.
miR-100 maintains phenotype of tumor-associated macrophages by targeting mTOR to promote tumor metastasis via Stat5a/IL-1ra pathway in mouse breast cancer
Authors: Wang Wei , Liu Yan , Guo Jian , He Huiwen , Mi Xue , Chen Chong , Xie Junling , Wang Shengnan , Wu Peng , Cao Fengqi , Bai Lipeng , Si Qin , Xiang Rong , Luo Yunping 
Published: December 2018

AbstractTumor-associated macrophages (TAMs), the main part of immune cells in tumor microenvironment (TME), play a potent role in promoting tumorigenesis through mechanisms such as stimulating angiogenesis, enhancing tumor migration and suppressing antitumor immunity. MicroRNAs (miRNAs) are considered as crucial regulators in multiple biological processes. The relationship between miRNAs and macrophages function has been extensively reported, but the roles that miRNAs play in regulating TAMs phenotype remain unclear. In this study, we screened highly expressed microRNAs in TAMs, and first identified that miR-100 represented a TAMs-high expression pattern and maintained TAMs phenotype by targeting mTOR signaling pathway. Moreover, miR-100 expression level in TAMs was positively related to IL-1ra secretion, a traditional immune-suppressive cytokine, which was determined to promote tumor cells stemness via stimulating Hedgehog pathway. Mechanism study suggested that mTOR/Stat5a pathway was involved in IL-1ra transcriptional regulation process mediated by miR-100. More importantly, tumor metastasis and invasion capacity were significantly decreased in a 4T1 mouse breast cancer model injected intratumorally with miR-100 antagomir, and combination therapy with cisplatin showed much better benefit. In this study, we confirm that highly expressed miR-100 maintains the phenotype of TAMs and promotes tumor metastasis via enhancing IL-1ra secretion. Interfering miR-100 expression of TAMs in mouse breast cancer model could inhibit TAMs pro-tumor function and reduce tumor metastasis, which suggests that miR-100 could serve as a potential therapy target to remodel tumor microenvironment in breast cancer.
A virus-encoded type I interferon decoy receptor enables evasion of host immunity through cell-surface binding
Authors: Hernáez Bruno , Alonso-Lobo Juan Manuel , Montanuy Imma , Fischer Cornelius , Sauer Sascha , Sigal Luis , Sevilla Noemí , Alcamí Antonio 
Published: December 2018

AbstractSoluble cytokine decoy receptors are potent immune modulatory reagents with therapeutic applications. Some virus-encoded secreted cytokine receptors interact with glycosaminoglycans expressed at the cell surface, but the biological significance of this activity in vivo is poorly understood. Here, we show the type I interferon binding protein (IFNα/βBP) encoded by vaccinia and ectromelia viruses requires of this cell binding activity to confer full virulence to these viruses and to retain immunomodulatory activity. Expression of a variant form of the IFNα/βBP that inhibits IFN activity, but does not interact with cell surface glycosaminoglycans, results in highly attenuated viruses with a virulence similar to that of the IFNα/βBP deletion mutant viruses. Transcriptomics analysis and infection of IFN receptor-deficient mice confirmed that the control of IFN activity is the main function of the IFNα/βBP in vivo. We propose that retention of secreted cytokine receptors at the cell surface may largely enhance their immunomodulatory activity.
Geometric quenching of orbital pair breaking in a single crystalline superconducting nanomesh network
Authors: Nam Hyoungdo , Chen Hua , Adams Philip W. , Guan Syu-You , Chuang Tien-Ming , Chang Chia-Seng , MacDonald Allan H. , Shih Chih-Kang 
Published: December 2018

AbstractIn a superconductor Cooper pairs condense into a single state and in so doing support dissipation free charge flow and perfect diamagnetism. In a magnetic field the minimum kinetic energy of the Cooper pairs increases, producing an orbital pair breaking effect. We show that it is possible to significantly quench the orbital pair breaking effect for both parallel and perpendicular magnetic fields in a thin film superconductor with lateral nanostructure on a length scale smaller than the magnetic length. By growing an ultra-thin (2 nm thick) single crystalline Pb nanowire network, we establish nm scale lateral structure without introducing weak links. Our network suppresses orbital pair breaking for both perpendicular and in-plane fields with a negligible reduction in zero-field resistive critical temperatures. Our study opens a frontier in nanoscale superconductivity by providing a strategy for maintaining pairing in strong field environments in all directions with important technological implications.
The open-ocean missing backscattering is in the structural complexity of particles
Authors: Organelli Emanuele , Dall’Olmo Giorgio , Brewin Robert J. W. , Tarran Glen A. , Boss Emmanuel , Bricaud Annick 
Published: December 2018

AbstractMarine microscopic particles profoundly impact global biogeochemical cycles, but our understanding of their dynamics is hindered by lack of observations. To fill this gap, optical backscattering measured by satellite sensors and in-situ autonomous platforms can be exploited. Unfortunately, these observations remain critically limited by an incomplete mechanistic understanding of what particles generate the backscattering signal. To achieve this understanding, optical models are employed. The simplest of these models—the homogeneous sphere—severely underestimates the measured backscattering and the missing signal has been attributed to submicron particles. This issue is known as the missing backscattering enigma. Here we show that a slightly more complex optical model—the coated sphere—can predict the measured backscattering and suggests that most of the signal comes from particles >1 µm. These findings were confirmed by independent size-fractionation experiments. Our results demonstrate that the structural complexity of particles is critical to understand open-ocean backscattering and contribute to solving the enigma.
An electrogenic redox loop in sulfate reduction reveals a likely widespread mechanism of energy conservation
Authors: Duarte Américo G. , Catarino Teresa , White Gaye F. , Lousa Diana , Neukirchen Sinje , Soares Cláudio M. , Sousa Filipa L. , Clarke Thomas A. , Pereira Inês A. C. 
Published: December 2018

AbstractThe bioenergetics of anaerobic metabolism frequently relies on redox loops performed by membrane complexes with substrate- and quinone-binding sites on opposite sides of the membrane. However, in sulfate respiration (a key process in the biogeochemical sulfur cycle), the substrate- and quinone-binding sites of the QrcABCD complex are periplasmic, and their role in energy conservation has not been elucidated. Here we show that the QrcABCD complex of Desulfovibrio vulgaris is electrogenic, as protons and electrons required for quinone reduction are extracted from opposite sides of the membrane, with a H+/e− ratio of 1. Although the complex does not act as a H+-pump, QrcD may include a conserved proton channel leading from the N-side to the P-side menaquinone pocket. Our work provides evidence of how energy is conserved during dissimilatory sulfate reduction, and suggests mechanisms behind the functions of related bacterial respiratory complexes in other bioenergetic contexts.
Ezh2 programs TFH differentiation by integrating phosphorylation-dependent activation of Bcl6 and polycomb-dependent repression of p19Arf
Authors: Li Fengyin , Zeng Zhouhao , Xing Shaojun , Gullicksrud Jodi A. , Shan Qiang , Choi Jinyong , Badovinac Vladimir P. , Crotty Shane , Peng Weiqun , Xue Hai-Hui 
Published: December 2018

AbstractEzh2 is an histone methyltransferase (HMT) that catalyzes H3K27me3 and functions in TH1, TH2, and Treg cells primarily via HMT activity. Here we show that Ezh2 ablation impairs T follicular helper (TFH) cell differentiation and activation of the TFH transcription program. In TFH cells, most Ezh2-occupied genomic sites, including the Bcl6 promoter, are associated with H3K27ac rather than H3K27me3. Mechanistically, Ezh2 is recruited by Tcf1 to directly activate Bcl6 transcription, with this function requiring Ezh2 phosphorylation at Ser21. Meanwhile, Ezh2 deploys H3K27me3 to repress Cdkn2a expression in TFH cells, where aberrantly upregulated p19Arf, a Cdkn2a protein product, triggers TFH cell apoptosis and antagonizes Bcl6 function via protein-protein interaction. Either forced expression of Bcl6 or genetic ablation of p19Arf in Ezh2-deficient cells improves TFH cell differentiation and helper function. Thus, Ezh2 orchestrates TFH-lineage specification and function maturation by integrating phosphorylation-dependent transcriptional activation and HMT-dependent gene repression.
Serine synthesis through PHGDH coordinates nucleotide levels by maintaining central carbon metabolism
Authors: Reid Michael A. , Allen Annamarie E. , Liu Shiyu , Liberti Maria V. , Liu Pei , Liu Xiaojing , Dai Ziwei , Gao Xia , Wang Qian , Liu Ying , Lai Luhua , Locasale Jason W. 
Published: December 2018

AbstractPhosphoglycerate dehydrogenase (PHGDH) catalyzes the committed step in de novo serine biosynthesis. Paradoxically, PHGDH and serine synthesis are required in the presence of abundant environmental serine even when serine uptake exceeds the requirements for nucleotide synthesis. Here, we establish a mechanism for how PHGDH maintains nucleotide metabolism. We show that inhibition of PHGDH induces alterations in nucleotide metabolism independent of serine utilization. These changes are not attributable to defects in serine-derived nucleotide synthesis and redox maintenance, another key aspect of serine metabolism, but result from disruption of mass balance within central carbon metabolism. Mechanistically, this leads to simultaneous alterations in both the pentose phosphate pathway and the tri-carboxylic acid cycle, as we demonstrate based on a quantitative model. These findings define a mechanism whereby disruption of one metabolic pathway induces toxicity by simultaneously affecting the activity of multiple related pathways.
Broadband single molecule SERS detection designed by warped optical spaces
Authors: Mao Peng , Liu Changxu , Favraud Gael , Chen Qiang , Han Min , Fratalocchi Andrea , Zhang Shuang 
Published: December 2018

AbstractEngineering hotspots is of crucial importance in many applications including energy harvesting, nano-lasers, subwavelength imaging, and biomedical sensing. Surface-enhanced Raman scattering spectroscopy is a key technique to identify analytes that would otherwise be difficult to diagnose. In standard systems, hotspots are realised with nanostructures made by acute tips or narrow gaps. Owing to the low probability for molecules to reach such tiny active regions, high sensitivity is always accompanied by a large preparation time for analyte accumulation which hinders the time response. Inspired by transformation optics, we introduce an approach based on warped spaces to manipulate hotspots, resulting in broadband enhancements in both the magnitude and volume. Experiments for single molecule detection with a fast soaking time are realised in conjunction with broadband response and uniformity. Such engineering could provide a new design platform for a rich manifold of devices, which can benefit from broadband and huge field enhancements.
Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy
Authors: Whitney James B. , Lim So-Yon , Osuna Christa E. , Kublin Jessica L. , Chen Elsa , Yoon Gyeol , Liu Po-Ting , Abbink Peter , Borducci Erica N. , Hill Alison , Lewis Mark G. , Geleziunas Romas , Robb Merlin L. , Michael Nelson L. , Barouch Dan H. 
Published: December 2018

AbstractThe precise time when the viral reservoir is seeded during acute HIV-1 infection remains unclear. We previously demonstrated that the viral reservoir was seeded by day 3 following SIVmac251 infection in rhesus monkeys. Here we report the impact of initiating ART on day 0 (6 h), 1, 2, or 3 following intrarectal SIVmac251 infection in 20 rhesus monkeys (N = 5/group). After 6 months of daily suppressive ART, antiretroviral drugs were discontinued, and viral rebound was monitored. 0% (0 of 5), 20% (1 of 5), 60% (3 of 5), and 100% (5 of 5) of animals that initiated ART on days 0 (6 h), 1, 2, or 3, respectively, showed viral rebound following ART discontinuation and correlated with integrated viral DNA in lymph node CD4+ T cells. These data demonstrate that the viral reservoir is seeded within the first few days of infection and that early ART initiation limits the viral reservoir.
Population reconstructions for humans and megafauna suggest mixed causes for North American Pleistocene extinctions
Authors: Broughton Jack M. , Weitzel Elic M. 
Published: December 2018

AbstractDozens of large mammals such as mammoth and mastodon disappeared in North America at the end of the Pleistocene with climate change and “overkill” by human hunters the most widely-argued causes. However, the population dynamics of humans and megafauna preceding extinctions have received little attention even though such information may be telling as we expect increasing human populations to be correlated with megafaunal declines if hunting caused extinctions. No such trends are expected if climate change was the primary cause. We present tests of these hypotheses here by using summed calibrated radiocarbon date distributions to reconstruct population levels of megafauna and humans. The results suggest that the causes for extinctions varied across taxa and by region. In three cases, extinctions appear linked to hunting, while in five others they are consistent with the ecological effects of climate change and in a final case, both hunting and climate change appear responsible.
Optimized libraries for CRISPR-Cas9 genetic screens with multiple modalities
Authors: Sanson Kendall R. , Hanna Ruth E. , Hegde Mudra , Donovan Katherine F. , Strand Christine , Sullender Meagan E. , Vaimberg Emma W. , Goodale Amy , Root David E. , Piccioni Federica , Doench John G. 
Published: December 2018

AbstractThe creation of genome-wide libraries for CRISPR knockout (CRISPRko), interference (CRISPRi), and activation (CRISPRa) has enabled the systematic interrogation of gene function. Here, we show that our recently-described CRISPRko library (Brunello) is more effective than previously published libraries at distinguishing essential and non-essential genes, providing approximately the same perturbation-level performance improvement over GeCKO libraries as GeCKO provided over RNAi. Additionally, we present genome-wide libraries for CRISPRi (Dolcetto) and CRISPRa (Calabrese), and show in negative selection screens that Dolcetto, with fewer sgRNAs per gene, outperforms existing CRISPRi libraries and achieves comparable performance to CRISPRko in detecting essential genes. We also perform positive selection CRISPRa screens and demonstrate that Calabrese outperforms the SAM approach at identifying vemurafenib resistance genes. We further compare CRISPRa to genome-scale libraries of open reading frames (ORFs). Together, these libraries represent a suite of genome-wide tools to efficiently interrogate gene function with multiple modalities.
Field-level clothianidin exposure affects bumblebees but generally not their pathogens
Authors: Wintermantel Dimitry , Locke Barbara , Andersson Georg K. S. , Semberg Emilia , Forsgren Eva , Osterman Julia , Rahbek Pedersen Thorsten , Bommarco Riccardo , Smith Henrik G. , Rundlöf Maj , de Miranda Joachim R. 
Published: December 2018

AbstractNeonicotinoids are implicated in bee declines and laboratory studies imply that they impair the bee immune system, thereby precipitating a rise in pathogen levels. To establish whether such synergisms reduce bee performance in real-world agricultural landscapes, we analysed the microbial composition of the bumblebee (Bombus terrestris) samples from our recent landscape study on the impacts of field-level clothianidin exposure. We related clothianidin exposure and microbial composition to both individual- and colony-level performance parameters, to better understand the direct and indirect mechanistic effects of neonicotinoid exposure on bumblebees. We show that exposure to clothianidin from seed-coated oilseed rape reduces bumblebee size and numbers, particularly of reproductives. However, exposure does not affect the levels of non-pathogenic bacteria or viruses, nor induce rises in the levels or virulence of intracellular parasites. We conclude that field exposure to the neonicotinoid clothianidin affects bumblebee performance but generally not their pathogenic or beneficial microbiota.
Detecting the dominance component of heritability in isolated and outbred human populations
Authors: Herzig Anthony F. , Nutile Teresa , Ruggiero Daniela , Ciullo Marina , Perdry Hervé , Leutenegger Anne-Louise 
Published: December 2018

AbstractInconsistencies between published estimates of dominance heritability between studies of human genetic isolates and human outbred populations incite investigation into whether such differences result from particular trait architectures or specific population structures. We analyse simulated datasets, characteristic of genetic isolates and of unrelated individuals, before analysing the isolate of Cilento for various commonly studied traits. We show the strengths of using genetic relationship matrices for variance decomposition over identity-by-descent based methods in a population isolate and that heritability estimates in isolates will avoid the downward biases that may occur in studies of samples of unrelated individuals; irrespective of the simulated distribution of causal variants. Yet, we also show that precise estimates of dominance in isolates are demonstrably problematic in the presence of shared environmental effects and such effects should be accounted for. Nevertheless, we demonstrate how studying isolates can help determine the existence or non-existence of dominance for complex traits, and we find strong indications of non-zero dominance for low-density lipoprotein level in Cilento. Finally, we recommend future study designs to analyse trait variance decomposition from ensemble data across multiple population isolates.