bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subtropical Cyclone Formation via Warm Seclusion Development: The Importance of Surface Fluxes
Authors: Quitián‐Hernández L. , González‐Alemán J. J. , Santos‐Muñoz D. , Fernández‐González S. , Valero F. , Martín M. L. 
Published: March 2020

AbstractSubtropical cyclones (STCs) are characterized by a thermal hybrid structure with tropical and extratropical features. STCs are considered a numerical modeling challenge because of their rapid intensification. A fundamental part of their strength is derived from diabatic processes associated with convection and heat fluxes from the ocean. This study evaluates the importance of surface turbulent heat fluxes during the transition of an extratropical precursor into a STC. This cyclone evolved embedded within a strong meridional flow, having a Shapiro‐Keyser structure and undergoing a warm seclusion process. To assess the importance of those heat fluxes, two Weather Research and Forecasting simulations were defined considering the presence and absence of those fluxes. Results of both simulations reveal a warm seclusion process, which weakened in absence of the heat fluxes. During the system genesis and in absence of heat fluxes, the wind and rainfall values were increased due to the remarkably intense area of frontogenesis to the northwest. Given these results and the lack of transition in the absence of heat fluxes, the frontal nature of the system was verified. Considering the heat fluxes, the obtained potential vorticity values diminished, reducing wind shear and intensifying convection in the system, which favored its transition into an STC. This study is groundbreaking in that no STC has been linked to a warm seclusion process in the Eastern North Atlantic. Additionally, simulated wind field shows an underestimation in comparison with Atmospheric Motion Vectors, used as observational data so as to give a weight to the wind analysis.
Synergetic Satellite Trend Analysis of Aerosol and Warm Cloud Properties ver Ocean and Its Implication for Aerosol‐Cloud Interactions
Authors: Bai Heming , Wang Minghuai , Zhang Zhibo , Liu Yawen 
Published: March 2020

AbstractDecadal‐scale trends in aerosol and cloud properties provide important ways for understanding aerosol‐cloud interactions. In this paper, by using MODIS products (2003–2017), we analyze synergetic trends in aerosol properties and warm cloud properties over global ocean. Cloud droplet number concentration (CDNC) and aerosol parameters (aerosol optical depth, angstrom exponent, and aerosol index) show consistent decreasing trend over East Coast of the United States (EUS), west coast of Europe (WEU), and east coast of China (EC), and no significant trend in liquid water path is found over these regions during the period 2003–2017. Over regions with significant long‐term trends of aerosol loading and CDNC (e.g., EUS and WEU), the sensitivity of CDNC to aerosol loading based on the long‐term trend is closer to those derived from ground and aircraft observations and larger than those derived from instantaneous satellite observations, providing an alternative way for quantifying aerosol‐cloud interactions. A clear shift in the normalized probability density function of CDNC between the first 5 years (2003–2007) and the last 5 years (2013–2017) is found, with a decrease of around 50% in the occurrence frequency of high CDNC (>400 cm−3) over EUS and WEU. The relative variances of cloud droplet effective radius generally decrease with decreasing aerosol loading, providing large‐scale evidence for the effects of anthropogenic aerosols on the dispersion of cloud droplet size distribution. The long‐term satellite data sets provide great opportunities for quantifying aerosol‐cloud interactions and further confronting these interactions in climate models in the future.
Confronting Arctic Troposphere, Clouds, and Surface Energy Budget Representations in Regional Climate Models With Observations
Authors: Sedlar Joseph , Tjernström Michael , Rinke Annette , Orr Andrew , Cassano John , Fettweis Xavier , Heinemann Günther , Seefeldt Mark , Solomon Amy , Matthes Heidrun , Phillips Tony , Webster Stuart 
Published: March 2020

AbstractA coordinated regional climate model (RCM) evaluation and intercomparison project based on observations from a July–October 2014 trans‐Arctic Ocean field experiment (ACSE‐Arctic Clouds during Summer Experiment) is presented. Six state‐of‐the‐art RCMs were constrained with common reanalysis lateral boundary forcing and upper troposphere nudging techniques to explore how the RCMs represented the evolution of the surface energy budget (SEB) components and their relation to cloud properties. We find that the main reasons for the modeled differences in the SEB components are a direct consequence of the RCM treatment of cloud and cloud‐radiative interactions. The RCMs could be separated into groups by their overestimation or underestimation of cloud liquid. While radiative and turbulent heat flux errors were relatively large, they often invoke compensating errors. In addition, having the surface sea‐ice concentrations constrained by the reanalysis or satellite observations limited how errors in the modeled radiative fluxes could affect the SEB and ultimately the surface evolution and its coupling with lower tropospheric mixing and cloud properties. Many of these results are consistent with RCM biases reported in studies over a decade ago. One of the six models was a fully coupled ocean‐ice‐atmosphere model. Despite the biases in overestimating cloud liquid, and associated SEB errors due to too optically thick clouds, its simulations were useful in understanding how the fully coupled system is forced by, and responds to, the SEB evolution. Moving forward, we suggest that development of RCM studies need to consider the fully coupled climate system.
Controls Over Particle Motion and Resting Times of Coarse Bed Load Transport in a Glacier‐Fed Mountain Stream
Authors: Mao Luca , Toro Matteo , Carrillo Ricardo , Brardinoni Francesco , Fraccarollo Luigi 
Published: March 2020

AbstractCoarse bed load transport is a crucial process in river morphodynamics but is difficult to monitor in mountain streams. Here we present a new sediment transport data set obtained from 2 years of field‐based monitoring (2014–2015) at the Estero Morales, a high‐gradient stream in the central Chilean Andes. This stream features step‐pool bed geometry and a glacier‐fed hydrologic regime characterized by abrupt daily fluctuations in discharge. Bed load was monitored directly using Bunte samplers and by surveying the mobility of passive integrated transponder (PIT) tags. We used the competence method to quantify the effective slope, which is the fraction of the topographical slope responsible for bed load transport. This accounts for only 10% of the topographical slope, confirming that most of the energy is dissipated on macroroughness elements. We used the displacement lengths of PIT tags to analyze displacement lengths and virtual velocity of a wide range of tracer sizes (38–415 mm). Bed load transport in the Estero Morales shown to be size‐selective, and the distance between steps influences the displacement lengths of PIT tags. Displacement lengths were also used to derive the statistics of flight distances and resting times. Our results show that the average length of flight scales inversely to grain size. This contradicts Einstein's conjecture about the linear relationship between grain size and intervals between resting periods in a steep step‐pool stream in ordinary flood conditions.
Potential therapeutic target for aging and age-related neurodegenerative diseases: the role of acid sphingomyelinase
Authors: Park Min Hee , Jin Hee Kyung , Bae Jae-sung 
Published: March 2020

AbstractAging, which is associated with age-related changes in physiological processes, is the most significant risk factor for the development and progression of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Accumulating evidence has indicated that sphingolipids are significant regulators that are associated with pathogenesis in aging and several age-related neurodegenerative diseases. In particular, abnormal levels of acid sphingomyelinase (ASM), one of the significant sphingolipid-metabolizing enzymes, have been found in the blood and some tissues under various neuropathological conditions. Moreover, recent studies have reported the importance of ASM as a critical mediator that contributes to pathologies in aging and age-related neurodegenerative diseases. In this review, we describe the pathophysiological processes that are regulated by ASM, focusing on the age-related neurodegenerative environment. Furthermore, we discuss novel insights into how new therapeutics targeting ASM may potentially lead to effective strategies to combat aging and age-related neurodegenerative diseases.
Combined inhibition of Notch and FLT3 produces synergistic cytotoxic effects in FLT3/ITD+ acute myeloid leukemia
Authors: Li Dan , Li Tongjuan , Shang Zhen , Zhao Lei , Xu Qian , Tan Jiaqi , Qin Yun , Zhang Yuanyuan , Cao Yang , Wang Na , Huang Liang , Zhu Xiaojian , Zhou Kuangguo , Chen Liting , Li Chunrui , Xie Ting , Yang Yi , Wang Jue , Zhou Jianfeng 
Published: March 2020

AbstractInternal tandem duplication (ITD) mutations of FMS-like tyrosine kinase-3 (FLT3) are the most frequent genetic alterations in acute myeloid leukemia (AML) and predict a poor prognosis. FLT3 tyrosine kinase inhibitors (TKIs) provide short-term clinical responses, but the long-term prognosis of FLT3/ITD+ AML patients remains poor. Notch signaling is important in numerous types of tumors. However, the role of Notch signaling in FLT3/ITD+ AML remains to be elucidated. In the current study, we found that Notch signaling was activated upon FLT3-TKI treatment in FLT3/ITD+ cell lines and primary cells. As Notch signaling can be blocked by γ-secretase inhibitors (GSIs), we examined the combinatorial antitumor efficacy of FLT3-TKIs and GSIs against FLT3/ITD+ AML and explored the underlying molecular mechanisms. As a result, we observed synergistic cytotoxic effects, and the treatment preferentially reduced cell proliferation and induced apoptosis in FLT3/ITD+ AML cell lines and in primary AML cells. Furthermore, the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in an FLT3/ITD+ patient-derived xenograft AML model. Mechanistically, differential expression analysis suggested that CXCR3 may be partially responsible for the observed synergy, possibly through ERK signaling. Our findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD+ AML.
An amber obligate active site-directed ligand evolution technique for phage display
Authors: Tharp Jeffery M. , Hampton J. Trae , Reed Catrina A. , Ehnbom Andreas , Chen Peng-Hsun Chase , Morse Jared S. , Kurra Yadagirri , Pérez Lisa M. , Xu Shiqing , Liu Wenshe Ray 
Published: March 2020

AbstractAlthough noncanonical amino acids (ncAAs) were first incorporated into phage libraries through amber suppression nearly two decades ago, their application for use in drug discovery has been limited due to inherent library bias towards sense-containing phages. Here, we report a technique based on superinfection immunity of phages to enrich amber-containing clones, thus avoiding the observed bias that has hindered incorporation of ncAAs into phage libraries. We then take advantage of this technique for development of active site-directed ligand evolution of peptides, where the ncAA serves as an anchor to direct the binding of its peptides to the target’s active site. To demonstrate this, phage-displayed peptide libraries are developed that contain a genetically encoded butyryl lysine and are subsequently used to select for ligands that bind SIRT2. These ligands are then modified to develop low nanomolar inhibitors of SIRT2.
Quantification of the overall contribution of gene-environment interaction for obesity-related traits
Authors: Sulc Jonathan , Mounier Ninon , Günther Felix , Winkler Thomas , Wood Andrew R. , Frayling Timothy M. , Heid Iris M. , Robinson Matthew R. , Kutalik Zoltán 
Published: March 2020

AbstractThe growing sample size of genome-wide association studies has facilitated the discovery of gene-environment interactions (GxE). Here we propose a maximum likelihood method to estimate the contribution of GxE to continuous traits taking into account all interacting environmental variables, without the need to measure any. Extensive simulations demonstrate that our method provides unbiased interaction estimates and excellent coverage. We also offer strategies to distinguish specific GxE from general scale effects. Applying our method to 32 traits in the UK Biobank reveals that while the genetic risk score (GRS) of 376 variants explains 5.2% of body mass index (BMI) variance, GRSxE explains an additional 1.9%. Nevertheless, this interaction holds for any variable with identical correlation to BMI as the GRS, hence may not be GRS-specific. Still, we observe that the global contribution of specific GRSxE to complex traits is substantial for nine obesity-related measures (including leg impedance and trunk fat-free mass).
Encoding of contextual fear memory in hippocampal–amygdala circuit
Authors: Kim Woong Bin , Cho Jun-Hyeong 
Published: March 2020

AbstractIn contextual fear conditioning, experimental subjects learn to associate a neutral context with an aversive stimulus and display fear responses to a context that predicts danger. Although the hippocampal–amygdala pathway has been implicated in the retrieval of contextual fear memory, the mechanism by which fear memory is encoded in this circuit has not been investigated. Here, we show that activity in the ventral CA1 (vCA1) hippocampal projections to the basal amygdala (BA), paired with aversive stimuli, contributes to encoding conditioned fear memory. Contextual fear conditioning induced selective strengthening of a subset of vCA1–BA synapses, which was prevented under anisomycin-induced retrograde amnesia. Moreover, a subpopulation of BA neurons receives stronger monosynaptic inputs from context-responding vCA1 neurons, whose activity was required for contextual fear learning and synaptic potentiation in the vCA1–BA pathway. Our study suggests that synaptic strengthening of vCA1 inputs conveying contextual information to a subset of BA neurons contributes to encoding adaptive fear memory for the threat-predictive context.
An ankyrin-repeat and WRKY-domain-containing immune receptor confers stripe rust resistance in wheat
Authors: Wang Huan , Zou Shenghao , Li Yiwen , Lin Fanyun , Tang Dingzhong 
Published: March 2020

AbstractPerception of pathogenic effectors in plants often relies on nucleotide-binding domain (NBS) and leucine-rich-repeat-containing (NLR) proteins. Some NLRs contain additional domains that function as integrated decoys for pathogen effector targets and activation of immune signalling. Wheat stripe rust is one of the most devastating diseases of crop plants. Here, we report the cloning of YrU1, a stripe rust resistance gene from the diploid wheat Triticum urartu, the progenitor of the A genome of hexaploid wheat. YrU1 encodes a coiled-coil-NBS-leucine-rich repeat protein with N-terminal ankyrin-repeat and C-terminal WRKY domains, representing a unique NLR structure in plants. Database searches identify similar architecture only in wheat relatives. Transient expression of YrU1 in Nicotiana benthamiana does not induce cell death in the absence of pathogens. The ankyrin-repeat and coiled-coil domains of YrU1 self-associate, suggesting that homodimerisation is critical for YrU1 function. The identification and cloning of this disease resistance gene sheds light on NLR protein function and may facilitate breeding to control the devastating wheat stripe rust disease.
Colossal oxygen vacancy formation at a fluorite-bixbyite interface
Authors: Lee Dongkyu , Gao Xiang , Sun Lixin , Jee Youngseok , Poplawsky Jonathan , Farmer Thomas O. , Fan Lisha , Guo Er-Jia , Lu Qiyang , Heller William T. , Choi Yongseong , Haskel Daniel , Fitzsimmons Michael R. , Chisholm Matthew F. , Huang Kevin , Yildiz Bilge , Lee Ho Nyung 
Published: March 2020

AbstractOxygen vacancies in complex oxides are indispensable for information and energy technologies. There are several means to create oxygen vacancies in bulk materials. However, the use of ionic interfaces to create oxygen vacancies has not been fully explored. Herein, we report an oxide nanobrush architecture designed to create high-density interfacial oxygen vacancies. An atomically well-defined (111) heterointerface between the fluorite CeO2 and the bixbyite Y2O3 is found to induce a charge modulation between Y3+ and Ce4+ ions enabled by the chemical valence mismatch between the two elements. Local structure and chemical analyses, along with theoretical calculations, suggest that more than 10% of oxygen atoms are spontaneously removed without deteriorating the lattice structure. Our fluorite–bixbyite nanobrush provides an excellent platform for the rational design of interfacial oxide architectures to precisely create, control, and transport oxygen vacancies critical for developing ionotronic and memristive devices for advanced energy and neuromorphic computing technologies.
Phosphoproteomics identifies a bimodal EPHA2 receptor switch that promotes embryonic stem cell differentiation
Authors: Fernandez-Alonso Rosalia , Bustos Francisco , Budzyk Manon , Kumar Pankaj , Helbig Andreas O. , Hukelmann Jens , Lamond Angus I. , Lanner Fredrik , Zhou Houjiang , Petsalaki Evangelia , Findlay Greg M. 
Published: March 2020

AbstractEmbryonic Stem Cell (ESC) differentiation requires complex cell signalling network dynamics, although the key molecular events remain poorly understood. Here, we use phosphoproteomics to identify an FGF4-mediated phosphorylation switch centred upon the key Ephrin receptor EPHA2 in differentiating ESCs. We show that EPHA2 maintains pluripotency and restrains commitment by antagonising ERK1/2 signalling. Upon ESC differentiation, FGF4 utilises a bimodal strategy to disable EPHA2, which is accompanied by transcriptional induction of EFN ligands. Mechanistically, FGF4-ERK1/2-RSK signalling inhibits EPHA2 via Ser/Thr phosphorylation, whilst FGF4-ERK1/2 disrupts a core pluripotency transcriptional circuit required for Epha2 gene expression. This system also operates in mouse and human embryos, where EPHA receptors are enriched in pluripotent cells whilst surrounding lineage-specified trophectoderm expresses EFNA ligands. Our data provide insight into function and regulation of EPH-EFN signalling in ESCs, and suggest that segregated EPH-EFN expression coordinates cell fate with compartmentalisation during early embryonic development.
Nucleosome positioning stability is a modulator of germline mutation rate variation across the human genome
Authors: Li Cai , Luscombe Nicholas M. 
Published: March 2020

AbstractNucleosome organization has been suggested to affect local mutation rates in the genome. However, the lack of de novo mutation and high-resolution nucleosome data has limited the investigation of this hypothesis. Additionally, analyses using indirect mutation rate measurements have yielded contradictory and potentially confounding results. Here, we combine data on >300,000 human de novo mutations with high-resolution nucleosome maps and find substantially elevated mutation rates around translationally stable (‘strong’) nucleosomes. We show that the mutational mechanisms affected by strong nucleosomes are low-fidelity replication, insufficient mismatch repair and increased double-strand breaks. Strong nucleosomes preferentially locate within young SINE/LINE transposons, suggesting that when subject to increased mutation rates, transposons are then more rapidly inactivated. Depletion of strong nucleosomes in older transposons suggests frequent positioning changes during evolution. The findings have important implications for human genetics and genome evolution.
Locally-adapted reproductive photoperiodism determines population vulnerability to climate change in burying beetles
Authors: Tsai Hsiang-Yu , Rubenstein Dustin R. , Fan Yu-Meng , Yuan Tzu-Neng , Chen Bo-Fei , Tang Yezhong , Chen I-Ching , Shen Sheng-Feng 
Published: March 2020

AbstractUnderstanding how phenotypic traits vary among populations inhabiting different environments is critical for predicting a species’ vulnerability to climate change. Yet, little is known about the key functional traits that determine the distribution of populations and the main mechanisms—phenotypic plasticity vs. local adaptation—underlying intraspecific functional trait variation. Using the Asian burying beetleNicrophorus nepalensis, we demonstrate that mountain ranges differing in elevation and latitude offer unique thermal environments in which two functional traits—thermal tolerance and reproductive photoperiodism—interact to shape breeding phenology. We show that populations on different mountain ranges maintain similar thermal tolerances, but differ in reproductive photoperiodism. Through common garden and reciprocal transplant experiments, we confirm that reproductive photoperiodism is locally adapted and not phenotypically plastic. Accordingly, year-round breeding populations on mountains of intermediate elevation are likely to be most susceptible to future warming because maladaptation occurs when beetles try to breed at warmer temperatures.
Small molecule regulated sgRNAs enable control of genome editing in E. coli by Cas9
Authors: Iwasaki Roman S. , Ozdilek Bagdeser A. , Garst Andrew D. , Choudhury Alaksh , Batey Robert T. 
Published: March 2020

AbstractCRISPR-Cas9 has led to great advances in gene editing for a broad spectrum of applications. To further the utility of Cas9 there have been efforts to achieve temporal control over its nuclease activity. While different approaches have focused on regulation of CRISPR interference or editing in mammalian cells, none of the reported methods enable control of the nuclease activity in bacteria. Here, we develop RNA linkers to combine theophylline- and 3-methylxanthine (3MX)-binding aptamers with the sgRNA, enabling small molecule-dependent editing in Escherichia coli. These activatable guide RNAs enable temporal and post-transcriptional control of in vivo gene editing. Further, they reduce the death of host cells caused by cuts in the genome, a major limitation of CRISPR-mediated bacterial recombineering.
Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors
Authors: Barry Devin M. , Liu Xue-Ting , Liu Benlong , Liu Xian-Yu , Gao Fang , Zeng Xiansi , Liu Juan , Yang Qianyi , Wilhelm Steven , Yin Jun , Tao Ailin , Chen Zhou-Feng 
Published: March 2020

AbstractGastrin-releasing peptide (GRP) functions as a neurotransmitter for non-histaminergic itch, but its site of action (sensory neurons vs spinal cord) remains controversial. To determine the role of GRP in sensory neurons, we generated a floxed Grp mouse line. We found that conditional knockout of Grp in sensory neurons results in attenuated non-histaminergic itch, without impairing histamine-induced itch. Using a Grp-Cre knock-in mouse line, we show that the upper epidermis of the skin is exclusively innervated by GRP fibers, whose activation via optogeneics and chemogenetics in the skin evokes itch- but not pain-related scratching or wiping behaviors. In contrast, intersectional genetic ablation of spinal Grp neurons does not affect itch nor pain transmission, demonstrating that spinal Grp neurons are dispensable for itch transmission. These data indicate that GRP is a neuropeptide in sensory neurons for non-histaminergic itch, and GRP sensory neurons are dedicated to itch transmission.