bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Nearly Frontal and Highly Inclined Interplanetary Shocks on High‐Latitude Field‐Aligned Currents (FACs)
Authors: Shi Yining , Oliveira Denny M. , Knipp Delores J. , Zesta Eftyhia , Matsuo Tomoko , Anderson Brian 
Published: November 2019

AbstractWe present high‐latitude field‐aligned current (FAC) response to nearly frontal shocks (NFSs) and highly inclined shocks (HISs) through a superposed epoch analysis. The FACs are derived from magnetic perturbation data provided by the Active Magnetosphere and Planetary Electrodynamics Response Experiment program. Forty‐nine events for each group are used for the superposed epoch analysis. The 25%, 50%, and 75% quantiles of the FAC and total current distributions are studied. We found that NFSs are statistically stronger shocks in terms of solar wind parameters such as solar wind speed and interplanetary magnetic field.For the 50% quantiles, both groups of shocks produce rapid increases in total currents after shock arrival, but NFSs result in sharper increase in FACs and more intense FACs compared to HISs. At the 50% and 75% quantiles, NFSs trigger stronger auroral‐zone current disturbance for the first hour after shock arrival than do HISs. Spatially, the difference in FAC response is most notable in (1) the dayside noon region, (2) the duskside Region 2 current system, and (3) the dawnside prenoon Region 1 current system. Our results are consistent with previous numerical simulations that showed more symmetric and stronger compression of the magnetosphere for high‐speed and nearly frontal shocks. We observationally confirm the role of shock impact angle in controlling the subsequent shock geoeffectiveness for fast shocks. We assert that determining the shock impact angle via an upstream solar wind model could provide useful insight in forecasting the geoeffectiveness of a shock prior to its arrival at the magnetopause.
Imaginal retraining decreases craving for high-calorie food in overweight and obese women: A randomized controlled trial
Authors: Moritz Steffen , Göritz Anja S. , Schmotz Stella , Weierstall-Pust Roland , Gehlenborg Josefine , Gallinat Jürgen , Kühn Simone 
Published: November 2019

AbstractOverweight and obesity are epidemic conditions. Obesity is associated with somatic and psychological sequelae, including serious life-shortening disorders (e.g., diabetes). This study aimed to evaluate the efficacy of a newly developed imaginal variant of approach bias modification (i.e., imaginal retraining) for the reduction of craving for high-calorie food. In a randomized controlled trial, 384 women with a body mass index above 25 were allocated to a wait-list control group or to two variants of imaginal retraining (ratio: 1; 0.5; 0.5). The two intervention groups were sent a manual on imaginal retraining. One group was explicitly encouraged and instructed to use electronic reminders (RER); the standard retraining group (RS) was not encouraged to use electronic reminders. Assessments were 6 weeks apart and were carried out online. Craving for high-calorie food represented the primary outcome (based on the Visual Analog Scale, VAS). Secondary outcomes included the Food Cravings Questionnaire (FCQ-T-R). The study was registered as DRKS00017220. Women in the RER group utilized the retraining technique more often than those in the RS condition, and utilization frequency in turn was associated with improvement on craving and eating behavior scales. Both intention-to-treat and per-protocol analyses showed a favorable effect of the RER group, which achieved significance on the primary outcome, as well as on several other outcomes relative to controls at a small to medium effect size. For those participants who measured their weight before and after the assessment using a scale, weight loss in the RER group was significantly greater compared to the control group. Both retraining groups (RER: 39.4%; RS: 31.1%) reduced their subjective amount of eating relative to controls (24.2%). Approximately two-thirds of the sample (68.3%) performed the exercises at least once during the study period. The present results show that, when used regularly, imaginal retraining may reduce craving for high-calorie food in overweight and obese women. Of note, there was also evidence suggestive of weight reduction, although no diet or lifestyle change was recommended in the manual. Because a large subgroup neither read the manual nor performed the exercises, we recommend that future imaginal retraining be conveyed via short video clips.
Cerebrospinal fluid oxidative stress metabolites in patients with bipolar disorder and healthy controls: a longitudinal case-control study
Authors: Knorr Ulla , Simonsen Anja Hviid , Roos Peter , Weimann Allan , Henriksen Trine , Christensen Ellen-Margrethe , Vinberg Maj , Mikkelsen Rie Lambæk , Kirkegaard Thomas , Jensen Rasmus Nejst , Akhøj Morten , Forman Julie , Poulsen Henrik Enghusen , Hasselbalch Steen Gregers , Kessing Lars Vedel 
Published: November 2019

AbstractBipolar disorder (BD) is a mental disorder characterized by recurrent relapses of affective episodes, cognitive impairment, illness progression, and reduced life expectancy. Increased systemic oxidatively generated nucleoside damage have been found in some neurodegenerative disorders and in BD. As the first, this naturalistic prospective, longitudinal follow-up case-control study investigated cerebrospinal fluid (CSF) oxidative stress markers 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) that relate to RNA and DNA damage, respectively. Patients with BD (n = 86, 51% female) and gender-and-age-matched healthy control individuals (HC; n = 44, 44% female) were evaluated at baseline (T0), during (T1) and after a new affective episode (T2), if it occurred, and after a year (T3). Cerebrospinal and urine oxidative stress markers were analyzed using ultra-performance liquid chromatography–tandem mass spectrometry. CSF-8-oxoGuo was statistically significantly higher by 18% (p = 0.003) in BD versus HC at T0, and by 22% (p = 0) at T3. CSF-8-oxoGuo had increased by 15% (p = 0.042) from T0 to T3, and by 14% (p = 0.021) from T2 to T3 in patients, who experienced an episode during follow-up. CSF-8-oxodG had increased by 26% (p = 0.054) from T0 to T2 and decreased by 19% (p = 0.041) from T2 to T3 in patients, who experienced an episode during follow-up. CSF-8-oxoGuo did not show a statistically significant change in HC during the one-year follow-up. CSF and urine-8-oxoGuo levels correlated moderately. In conclusion, CSF oxidative stress marker of RNA damage 8-oxoGuo showed both state and trait dependence in BD and stability in HC. Central RNA damage may be a potential biomarker for BD.
Aldo-keto reductases protect metastatic melanoma from ER stress-independent ferroptosis
Authors: Gagliardi Mara , Cotella Diego , Santoro Claudio , Corà Davide , Barlev Nickolai A. , Piacentini Mauro , Corazzari Marco 
Published: November 2019

AbstractThe incidence of melanoma is increasing over the years with a still poor prognosis and the lack of a cure able to guarantee an adequate survival of patients. Although the new immuno-based coupled to target therapeutic strategy is encouraging, the appearance of targeted/cross-resistance and/or side effects such as autoimmune disorders could limit its clinical use. Alternative therapeutic strategies are therefore urgently needed to efficiently kill melanoma cells. Ferroptosis induction and execution were evaluated in metastasis-derived wild-type and oncogenic BRAF melanoma cells, and the process responsible for the resistance has been dissected at molecular level. Although efficiently induced in all cells, in an oncogenic BRAF- and ER stress-independent way, most cells were resistant to ferroptosis execution. At molecular level we found that: resistant cells efficiently activate NRF2 which in turn upregulates the early ferroptotic marker CHAC1, in an ER stress-independent manner, and the aldo-keto reductases AKR1C1 ÷ 3 which degrades the 12/15-LOX-generated lipid peroxides thus resulting in ferroptotic cell death resistance. However, inhibiting AKRs activity/expression completely resensitizes resistant melanoma cells to ferroptosis execution. Finally, we found that the ferroptotic susceptibility associated with the differentiation of melanoma cells cannot be applied to metastatic-derived cells, due to the EMT-associated gene expression reprogramming process. However, we identified SCL7A11 as a valuable marker to predict the susceptibility of metastatic melanoma cells to ferroptosis. Our results identify the use of pro-ferroptotic drugs coupled to AKRs inhibitors as a new valuable strategy to efficiently kill human skin melanoma cells.
Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases
Authors: Nie Anzheng , Sun Bao , Fu Zhihui , Yu Dongsheng 
Published: November 2019

AbstractAminoacyl-tRNA synthetases (ARSs) play a vital role in protein synthesis by linking amino acids to their cognate transfer RNAs (tRNAs). This typical function has been well recognized over the past few decades. However, accumulating evidence reveals that ARSs are involved in a wide range of physiological and pathological processes apart from translation. Strikingly, certain ARSs are closely related to different types of immune responses. In this review, we address the infection and immune responses induced by pathogen ARSs, as well as the potential anti-infective compounds that target pathogen ARSs. Meanwhile, we describe the functional mechanisms of ARSs in the development of immune cells. In addition, we focus on the roles of ARSs in certain immune diseases, such as autoimmune diseases, infectious diseases, and tumor immunity. Although our knowledge of ARSs in the immunological context is still in its infancy, research in this field may provide new ideas for the treatment of immune-related diseases.
Characterization of genetic subclonal evolution in pancreatic cancer mouse models
Authors: Niknafs Noushin , Zhong Yi , Moral John Alec , Zhang Lance , Shao Melody Xiaoshan , Lo April , Makohon-Moore Alvin , Iacobuzio-Donahue Christine A. , Karchin Rachel 
Published: November 2019

AbstractThe KPC mouse model, driven by the Kras and Trp53 transgenes, is well regarded for faithful recapitulation of human pancreatic cancer biology. However, the extent that this model recapitulates the subclonal evolution of this tumor type is unknown. Here we report evidence of continuing subclonal evolution after tumor initiation that largely reflect copy number alterations that target cellular processes of established significance in human pancreatic cancer. The evolutionary trajectories of the mouse tumors show both linear and branching patterns as well as clonal mixing. We propose the KPC model and derivatives have unexplored utility as a functional system to model the mechanisms and modifiers of tumor evolution.
Tumor diversity and the trade-off between universal cancer tasks
Authors: Hausser Jean , Szekely Pablo , Bar Noam , Zimmer Anat , Sheftel Hila , Caldas Carlos , Alon Uri 
Published: November 2019

AbstractRecent advances have enabled powerful methods to sort tumors into prognosis and treatment groups. We are still missing, however, a general theoretical framework to understand the vast diversity of tumor gene expression and mutations. Here we present a framework based on multi-task evolution theory, using the fact that tumors need to perform multiple tasks that contribute to their fitness. We find that trade-offs between tasks constrain tumor gene-expression to a continuum bounded by a polyhedron whose vertices are gene-expression profiles, each specializing in one task. We find five universal cancer tasks across tissue-types: cell-division, biomass and energy, lipogenesis, immune-interaction and invasion and tissue-remodeling. Tumors that specialize in a task are sensitive to drugs that interfere with this task. Driver, but not passenger, mutations tune gene-expression towards specialization in specific tasks. This approach can integrate additional types of molecular data into a framework of tumor diversity grounded in evolutionary theory.
Tidal wetland resilience to sea level rise increases their carbon sequestration capacity in United States
Authors: Wang Faming , Lu Xiaoliang , Sanders Christian J. , Tang Jianwu 
Published: November 2019

AbstractCoastal wetlands are large reservoirs of soil carbon (C). However, the annual C accumulation rates contributing to the C storage in these systems have yet to be spatially estimated on a large scale. We synthesized C accumulation rate (CAR) in tidal wetlands of the conterminous United States (US), upscaled the CAR to national scale, and predicted trends based on climate change scenarios. Here, we show that the mean CAR is 161.8 ± 6 g Cm−2 yr−1, and the conterminous US tidal wetlands sequestrate 4.2–5.0 Tg C yr−1. Relative sea level rise (RSLR) largely regulates the CAR. The tidal wetland CAR is projected to increase in this century and continue their C sequestration capacity in all climate change scenarios, suggesting a strong resilience to sea level rise. These results serve as a baseline assessment of C accumulation in tidal wetlands of US, and indicate a significant C sink throughout this century.
The ABCG2 multidrug transporter is a pump gated by a valve and an extracellular lid
Authors: Khunweeraphong Narakorn , Szöllősi Daniel , Stockner Thomas , Kuchler Karl 
Published: November 2019

AbstractThe human ATP-binding cassette transporter ABCG2 is a key to anticancer resistance and physiological detoxification. However, the molecular mechanism of substrate transport remains enigmatic. A hydrophobic di-leucine motif in the ABCG2 core separates a large intracellular cavity from a smaller upper cavity. We show that the di-leucine motif acts as a valve that controls drug extrusion. Moreover, the extracellular structure engages the re-entry helix and all extracellular loops to form a roof architecture on top of the upper cavity. Disulfide bridges and a salt bridge limit roof flexibility, but provide a lid-like function to control drug release. We propose that drug translocation from the central to the upper cavities through the valve is driven by a squeezing motion, suggesting that ABCG2 operates similar to a peristaltic pump. Finally, the roof contains essential residues, offering therapeutic options to block ABCG2 by either targeting the valve or essential residues in the roof.
The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status
Authors: Trigg Ricky M. , Lee Liam C. , Prokoph Nina , Jahangiri Leila , Reynolds C. Patrick , Amos Burke G. A. , Probst Nicola A. , Han Miaojun , Matthews Jamie D. , Lim Hong Kai , Manners Eleanor , Martinez Sonia , Pastor Joaquin , Blanco-Aparicio Carmen , Merkel Olaf , de los Fayos Alonso Ines Garces , Kodajova Petra , Tangermann Simone , Högler Sandra , Luo Ji , Kenner Lukas , Turner Suzanne D. 
Published: November 2019

AbstractResistance to anaplastic lymphoma kinase (ALK)-targeted therapy in ALK-positive non-small cell lung cancer has been reported, with the majority of acquired resistance mechanisms relying on bypass signaling. To proactively identify resistance mechanisms in ALK-positive neuroblastoma (NB), we herein employ genome-wide CRISPR activation screens of NB cell lines treated with brigatinib or ceritinib, identifying PIM1 as a putative resistance gene, whose high expression is associated with high-risk disease and poor survival. Knockdown of PIM1 sensitizes cells of differing MYCN status to ALK inhibitors, and in patient-derived xenografts of high-risk NB harboring ALK mutations, the combination of the ALK inhibitor ceritinib and PIM1 inhibitor AZD1208 shows significantly enhanced anti-tumor efficacy relative to single agents. These data confirm that PIM1 overexpression decreases sensitivity to ALK inhibitors in NB, and suggests that combined front-line inhibition of ALK and PIM1 is a viable strategy for the treatment of ALK-positive NB independent of MYCN status.
Tsc1-mTORC1 signaling controls striatal dopamine release and cognitive flexibility
Authors: Kosillo Polina , Doig Natalie M. , Ahmed Kamran M. , Agopyan-Miu Alexander H.C.W. , Wong Corinna D. , Conyers Lisa , Threlfell Sarah , Magill Peter J. , Bateup Helen S. 
Published: November 2019

AbstractTuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations in TSC1 or TSC2, which encode proteins that negatively regulate mTOR complex 1 (mTORC1). TSC is associated with significant cognitive, psychiatric, and behavioral problems, collectively termed TSC-Associated Neuropsychiatric Disorders (TAND), and the cell types responsible for these manifestations are largely unknown. Here we use cell type-specific Tsc1 deletion to test whether dopamine neurons, which modulate cognitive, motivational, and affective behaviors, are involved in TAND. We show that loss of Tsc1 and constitutive activation of mTORC1 in dopamine neurons causes somatodendritic hypertrophy, reduces intrinsic excitability, alters axon terminal structure, and impairs striatal dopamine release. These perturbations lead to a selective deficit in cognitive flexibility, preventable by genetic reduction of the mTOR-binding protein Raptor. Our results establish a critical role for Tsc1-mTORC1 signaling in setting the functional properties of dopamine neurons, and indicate that dopaminergic dysfunction may contribute to cognitive inflexibility in TSC.
Polar surface structure of oxide nanocrystals revealed with solid-state NMR spectroscopy
Authors: Chen Junchao , Wu Xin-Ping , Hope Michael A. , Qian Kun , Halat David M. , Liu Tao , Li Yuhong , Shen Li , Ke Xiaokang , Wen Yujie , Du Jia-Huan , Magusin Pieter C. M. M. , Paul Subhradip , Ding Weiping , Gong Xue-Qing , Grey Clare P. , Peng Luming 
Published: November 2019

AbstractCompared to nanomaterials exposing nonpolar facets, polar-faceted nanocrystals often exhibit unexpected and interesting properties. The electrostatic instability arising from the intrinsic dipole moments of polar facets, however, leads to different surface configurations in many cases, making it challenging to extract detailed structural information and develop structure-property relations. The widely used electron microscopy techniques are limited because the volumes sampled may not be representative, and they provide little chemical bonding information with low contrast of light elements. With ceria nanocubes exposing (100) facets as an example, here we show that the polar surface structure of oxide nanocrystals can be investigated by applying 17O and 1H solid-state NMR spectroscopy and dynamic nuclear polarization, combined with DFT calculations. Both CeO4-termination reconstructions and hydroxyls are present for surface polarity compensation and their concentrations can be quantified. These results open up new possibilities for investigating the structure and properties of oxide nanostructures with polar facets.
Human confidence judgments reflect reliability-based hierarchical integration of contextual information
Authors: Schustek Philipp , Hyafil Alexandre , Moreno-Bote Rubén 
Published: November 2019

AbstractOur immediate observations must be supplemented with contextual information to resolve ambiguities. However, the context is often ambiguous too, and thus it should be inferred itself to guide behavior. Here, we introduce a novel hierarchical task (airplane task) in which participants should infer a higher-level, contextual variable to inform probabilistic inference about a hidden dependent variable at a lower level. By controlling the reliability of past sensory evidence through varying the sample size of the observations, we find that humans estimate the reliability of the context and combine it with current sensory uncertainty to inform their confidence reports. Behavior closely follows inference by probabilistic message passing between latent variables across hierarchical state representations. Commonly reported inferential fallacies, such as sample size insensitivity, are not present, and neither did participants appear to rely on simple heuristics. Our results reveal uncertainty-sensitive integration of information at different hierarchical levels and temporal scales.
Analog errors in quantum annealing: doom and hope
Authors: Pearson Adam , Mishra Anurag , Hen Itay , Lidar Daniel A. 
Published: November 2019

AbstractQuantum annealing has the potential to provide a speedup over classical algorithms in solving optimization problems. Just as for any other quantum device, suppressing Hamiltonian control errors will be necessary before quantum annealers can achieve speedups. Such analog control errors are known to lead to $$J$$
J
-chaos, wherein the probability of obtaining the optimal solution, encoded as the ground state of the intended Hamiltonian, varies widely depending on the control error. Here, we show that $$J$$
J
-chaos causes a catastrophic failure of quantum annealing, in that the scaling of the time-to-solution metric becomes worse than that of a deterministic (exhaustive) classical solver. We demonstrate this empirically using random Ising spin glass problems run on the two latest generations of the D-Wave quantum annealers. We then proceed to show that this doomsday scenario can be mitigated using a simple error suppression and correction scheme known as quantum annealing correction (QAC). By using QAC, the time-to-solution scaling of the same D-Wave devices is improved to below that of the classical upper bound, thus restoring hope in the speedup prospects of quantum annealing.
An attenuated Zika virus NS4B protein mutant is a potent inducer of antiviral immune responses
Authors: Li Guangyu , Adam Awadalkareem , Luo Huanle , Shan Chao , Cao Zengguo , Fontes-Garfias Camila R. , Sarathy Vanessa V. , Teleki Cody , Winkelmann Evandro R. , Liang Yuejin , Sun Jiaren , Bourne Nigel , Barrett Alan D. T. , Shi Pei-Yong , Wang Tian 
Published: November 2019

AbstractLive attenuated vaccines (LAVs) are one of the most important strategies to control flavivirus diseases. The flavivirus nonstructural (NS) 4B proteins are a critical component of both the virus replication complex and evasion of host innate immunity. Here we have used site-directed mutagenesis of residues in the highly conserved N-terminal and central hydrophobic regions of Zika virus (ZIKV) NS4B protein to identify candidate attenuating mutations. Three single-site mutants were generated, of which the NS4B-C100S mutant was more attenuated than the other two mutants (NS4B-C100A and NS4B-P36A) in two immunocompromised mouse models of fatal ZIKV disease. The ZIKV NS4B-C100S mutant triggered stronger type 1 interferons and interleukin-6 production, and higher ZIKV-specific CD4+and CD8+T-cell responses, but induced similar titers of neutralization antibodies compared with the parent wild-type ZIKV strain and a previously reported candidate ZIKV LAV with a 10-nucleotide deletion in 3′-UTR (ZIKV-3′UTR-Δ10). Vaccination with ZIKV NS4B-C100S protected mice from subsequent WT ZIKV challenge. Furthermore, either passive immunization with ZIKV NS4B-C100S immune sera or active immunization with ZIKV NS4B-C100S followed by the depletion of T cells affords full protection from lethal WT ZIKV challenge. In summary, our results suggest that the ZIKV NS4B-C100S mutant may serve as a candidate ZIKV LAV due to its attenuated phenotype and high immunogenicity.