bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating Upper Atmospheric Joule Heating Using Cross‐Combination of Data for Two Moderate Substorm Cases
Authors: Kalafatoglu Eyiguler E. C. , Kaymaz Zerefsan , Frissell Nathaniel A. , Ruohoniemi J. M. , Rastätter Lutz 
Published: July 2018

AbstractIn this work, empirical relationships based on indices (AE, IL, and KP), an empirical model (Weimer‐2005), coupled space weather models (BATS‐R‐US+CRCM/RCM), and combinative methods (using data from SuperDARN for electric field and OVATION PRIME+IRI combination for the conductances) are employed to investigate the Joule heating (JH) variability during two isolated substorms on 8 March 2008. The results are compared according to substorm phases, magnetic local time sectors, magnetic latitudes, role of electric fields, ionospheric conductances, and neutral wind. Qualitatively, all methods exhibit similar variations in the estimated JH rates. AE‐dependent methods and the Weimer‐2005 model show the highest JH rates. The response of AE to the elevated Epsilon levels is found to be delayed up to 50 min, whereas the onsets and variations in the other methods are concurrent with Epsilon. The combination of OVATION Prime+IRI and SuperDARN provides values close to the (Foster et al., 1983, https://doi.org/10.1029/JA088iA06p04885) suggesting that it is representative enough to use for estimating the JH. The OVATION Prime+IRI and SuperDARN method can provide JH at any point in the solar cycle based on dynamic solar wind input. BATSRUS/CRCM conductances and electric fields are higher than BATSRUS/RCM leading to 2.5 times as much JH as estimated by BATSRUS/RCM on average. Neutral winds are found to comprise an overall 15% of total JH with a maximum of 25% in dusk sector during the expansion phase. We discuss that W05 and AE‐dependent methods overestimate the JH rates during the solar minimum since they are constructed using solar maximum data.
Cross-feeding modulates antibiotic tolerance in bacterial communities
Authors: Adamowicz Elizabeth M , Flynn Jeffrey , Hunter Ryan C , Harcombe William R 
Published: July 2018

Abstract
Microbes frequently rely on metabolites excreted by other bacterial species, but little is known about how this cross-feeding influences the effect of antibiotics. We hypothesized that when species rely on each other for essential metabolites, the minimum inhibitory concentration (MIC) for all species will drop to that of the “weakest link”—the species least resistant in monoculture. We tested this hypothesis in an obligate cross-feeding system that was engineered between Escherichia coli, Salmonella enterica, and Methylobacterium extorquens. The effect of tetracycline and ampicillin were tested on both liquid and solid media. In all cases, resistant species were inhibited at significantly lower antibiotic concentrations in the cross-feeding community than in monoculture or a competitive community. However, deviation from the “weakest link” hypothesis was also observed in cross-feeding communities apparently as result of changes in the timing of growth and cross-protection. Comparable results were also observed in a clinically relevant system involving facultative cross-feeding between Pseudomonas aeruginosa and an anaerobic consortium found in the lungs of cystic fibrosis patients. P. aeruginosa was inhibited by lower concentrations of ampicillin when cross-feeding than when grown in isolation. These results suggest that cross-feeding significantly alters tolerance to antibiotics in a variety of systems.
Bacterial community composition responds to changes in copepod abundance and alters ecosystem function in an Arctic mesocosm study
Authors: Tsagaraki Tatiana M , Pree Bernadette , Leiknes Øystein , Larsen Aud , Bratbak Gunnar , Øvreås Lise , Egge Jorun K , Spanek Roman , Paulsen Maria L , Olsen Yngvar , Vadstein Olav , Thingstad T F 
Published: July 2018

Abstract
Combining a minimum food web model with Arctic microbial community dynamics, we have suggested that top-down control by copepods can affect the food web down to bacterial consumption of organic carbon. Pursuing this hypothesis further, we used the minimum model to design and analyse a mesocosm experiment, studying the effect of high (+Z) and low (-Z) copepod density on resource allocation, along an organic-C addition gradient. In the Arctic, both effects are plausible due to changes in advection patterns (affecting copepods) and meltwater inputs (affecting carbon). The model predicts a trophic cascade from copepods via ciliates to flagellates, which was confirmed experimentally. Auto- and heterotrophic flagellates affect bacterial growth rate and abundance via competition for mineral nutrients and predation, respectively. In +Z, the model predicts low bacterial abundance and activity, and little response to glucose; as opposed to clear glucose consumption effects in –Z. We observed a more resilient bacterial response to high copepods and demonstrate this was due to changes in bacterial community equitability. Species able to use glucose to improve their competitive and/or defensive properties, became predominant. The observed shift from a SAR11-to a Psychromonodaceae – dominated community suggests the latter was pivotal in this modification of ecosystem function. We argue that this group used glucose to improve its defensive or its competitive abilities (or both). Adding such flexibility in bacterial traits to the model, we show how it creates the observed resilience to top-down manipulations observed in our experiment.
Single cell genomic and transcriptomic evidence for the use of alternative nitrogen substrates by anammox bacteria
Authors: Ganesh Sangita , Bertagnolli Anthony D , Bristow Laura A , Padilla Cory C , Blackwood Nigel , Aldunate Montserrat , Bourbonnais Annie , Altabet Mark A , Malmstrom Rex R , Woyke Tanja , Ulloa Osvaldo , Konstantinidis Konstantinos T , Thamdrup Bo , Stewart Frank J 
Published: July 2018

Abstract
Anaerobic ammonium oxidation (anammox) contributes substantially to ocean nitrogen loss, particularly in anoxic marine zones (AMZs). Ammonium is scarce in AMZs, raising the hypothesis that organic nitrogen compounds may be ammonium sources for anammox. Biochemical measurements suggest that the organic compounds urea and cyanate can support anammox in AMZs. However, it is unclear if anammox bacteria degrade these compounds to ammonium themselves, or rely on other organisms for this process. Genes for urea degradation have not been found in anammox bacteria, and genomic evidence for cyanate use for anammox is limited to a cyanase gene recovered from the sediment bacterium Candidatus Scalindua profunda. Here, analysis of Ca. Scalindua single amplified genomes from the Eastern Tropical North Pacific AMZ revealed genes for urea degradation and transport, as well as for cyanate degradation. Urease and cyanase genes were transcribed, along with anammox genes, in the AMZ core where anammox rates peaked. Homologs of these genes were also detected in meta-omic datasets from major AMZs in the Eastern Tropical South Pacific and Arabian Sea. These results suggest that anammox bacteria from different ocean regions can directly access organic nitrogen substrates. Future studies should assess if and under what environmental conditions these substrates contribute to the ammonium budget for anammox.
miR-34a exerts as a key regulator in the dedifferentiation of osteosarcoma via PAI-1–Sox2 axis
Authors: Zhang Yu , Pan Yubin , Xie Chunyuan , Zhang Yan 
Published: July 2018

AbstractOsteosarcoma (OS) is a malignant bone cancer with severe chromosomal abnormalities and genetic aberrations. Our previous work reported the dedifferentiation of OS, which is related to poor prognosis. However, the molecular mechanism that regulates OS dedifferentiation is still a subject of exploration. Emerging evidence has suggested that microRNAs (miRNAs) are associated with the pathogenesis of OS and could potentially be developed for use as diagnostic biomarkers and therapeutic strategies. In the present study, we intended to illustrate the role of miR-34a in the dedifferentiation of OS. Upregulation of miR-34a was observed while OS cells were induced into stem-like phenotype. Notably, inhibition of miR-34a could promote the reprogramming transition of OS. Further exploration on the downstream network of miR-34a identified that blocking plasminogen activator inhibitor-1 (PAI-1) expression could restrain OS dedifferentiation into cancer stem-like cells by downregulating SRY-related-HMG box (Sox) 2. We also showed that Sox2 overexpression rescued the suppression phenotype driven by PAI-1 inhibition. Conversely, PAI-1 inhibitor (PAI-039) could suppress the upregulation of Sox2 expression caused by miR-34a inhibition. Be applying bone extracellular matrix (BEM)-OS models, we demonstrated the phenotypic heterogeneity of OS cells, consistent with a strong concordance between PAI-1 and Sox2 expression levels. Taken together, our findings proved miR-34a to be a bona fide suppressor involved in the regulation of OS dedifferentiation. Targeting miR-34a or its direct target PAI-1 could offer new strategies for OS treatment.
The autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes
Authors: Chen Zi , Nie Sheng-Dan , Qu Min-Li , Zhou Di , Wu Liang-Yan , Shi Xia-Jie , Ma Ling-Ran , Li Xin , Zhou Shan-Lei , Wang Shan , Wu Jing 
Published: July 2018

AbstractThe accumulation of palmitic acid (PA), implicated in obesity, can induce apoptotic cell death and inflammation of astrocytes. Caveolin-1 (Cav-1), an essential protein for astrocytes survival, can be degraded by autophagy, which is a double-edge sword that can either promote cell survival or cell death. The aim of this study was to delineate whether the autophagic degradation of Cav-1 is involved in PA-induced apoptosis and inflammation in hippocampal astrocytes. In this study we found that: (1) PA caused apoptotic death and inflammation by autophagic induction; (2) Cav-1 was degraded by PA-induced autophagy and PA induced autophagy in a Cav-1-independent manner; (3) the degradation of Cav-1 was responsible for PA-induced autophagy-dependent apoptotic cell death and inflammation; (4) chronic high-fat diet (HFD) induced Cav-1 degradation, apoptosis, autophagy, and inflammation in the hippocampal astrocytes of rats. Our results suggest that the autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes. Therefore, Cav-1 may be a potential therapeutic target for central nervous system injuries caused by PA accumulation.
CCL5-deficiency enhances intratumoral infiltration of CD8+ T cells in colorectal cancer
Authors: Zhang Shengbo , Zhong Ming , Wang Chao , Xu Yanjie , Gao Wei-Qiang , Zhang Yan 
Published: July 2018

AbstractColorectal cancer (CRC) is the third most common solid tumor in the world and shows resistance to several immunotherapies, particularly immune checkpoint blockade which has therapeutic effects on many other types of cancer. Cytotoxic CD8+ T cell has been considered as one of the main populations of effector immune cells in antitumor immunity; however, the absence of CD8+ T cells in the central tumor area has become a major obstacle for solid tumor immunotherapy, particularly for CRC. Thus, novel therapeutic strategies that could promote CD8+ T cells to accumulate in the central tumor area are urgently needed. Here, we demonstrated that CCL5-deficiency delayed tumor growth and metastasis via facilitating CD8+ T cells to accumulate into tumor site in CRC mouse models. Furthermore, CCL5-deficiency could upregulate PD-1 and PD-L1 expression and reduce the resistance to anti-PD-1 antibody therapy in CRC mouse model. Mechanically, the results of RNA-sequencing, in vitro coculture system and hypoxia measurements demonstrated that knockdown of CCL5 could result in the metabolic disorders in CD11bhiF4/80low TAMs and suppress the expression of S100a9 to promote the migration of CD8+ T cells in the tumor microenvironment. These findings were verified by the data of clinical samples from CRC patients, suggesting that CCL5 may provide a potential therapeutic target for the combined PD-1-immunotherapy of CRC.
CUEDC2, a novel interacting partner of the SOCS1 protein, plays important roles in the leukaemogenesis of acute myeloid leukaemia
Authors: Wu Qing-Yun , Zhu Yuan-Yuan , Liu Yang , Wei Fang , Tong Yu-Xue , Cao Jiang , Zhou Ping , Niu Ming-Shan , Li Zhen-Yu , Zeng Ling-Yu , Li Feng , Xu Kai-Lin 
Published: July 2018

AbstractDownregulation of suppressor of cytokine signalling-1 (SOCS1) is one of the vital reasons for JAK1-STAT3 pathway activation in acute myeloid leukaemia (AML). CUE domain-containing 2 (CUEDC2) was a novel interacting partner of SOCS1 and a positive correlation between the expression of CUEDC2 and SOCS1 was confirmed in primary AML cells and AML cell lines without SOCS1 promoter methylation. We aimed to explore roles of CUEDC2 in regulating ubiquitin-mediated degradation of SOCS1 in the leukaemogenesis of AML.According to in vitro experiments, CUEDC2 overexpression increased the level of SOCS1 protein, suppressed JAK1-STAT3 pathway activation. The suppression of this pathway inhibited AML cells’ proliferation by causing G1 arrest and enhanced AML cells’ sensitivity to cytarabine and idarubicin. Similarity, downregulation of CUEDC2 produced opposite results. Knockout or low expression of CUEDC2 in mouse or AML patients displayed lower overall survival and event-free survival rates, compared with these mouse and AML patients had high-CUEDC2 expression. Mechanistic studies revealed that CUEDC2 overexpression attenuated SOCS1 ubiquitination, facilitated its stabilisation by enhancing SOCS1, Elongin C and Cullin-2 (CUL2) interactions, thus inhibited JAK1-STAT3 pathway and leukaemogenesis of AML. Therefore, our novel findings indicated that CUEDC2 interacted with SOCS1 to suppress SOCS1’s ubiquitin-mediated degradation, JAK1-STAT3 pathway activation and leukaemogenesis of AML.
Deep RNA sequencing reveals the dynamic regulation of miRNA, lncRNAs, and mRNAs in osteosarcoma tumorigenesis and pulmonary metastasis
Authors: Xie Lin , Yao Zhihong , Zhang Ya , Li Dongqi , Hu Fengdi , Liao Yedan , Zhou Ling , Zhou Yonghong , Huang Zeyong , He Zewei , Han Lei , Yang Yihao , Yang Zuozhang 
Published: July 2018

AbstractOsteosarcoma (OS) is the most common pediatric malignant bone tumor, and occurrence of pulmonary metastasis generally causes a rapid and fatal outcome. Here we aimed to provide clues for exploring the mechanism of tumorigenesis and pulmonary metastasis for OS by comprehensive analysis of microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA expression in primary OS and OS pulmonary metastasis. In this study, deep sequencing with samples from primary OS (n = 3), pulmonary metastatic OS (n = 3), and normal controls (n = 3) was conducted and differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs), and mRNAs (DEmRNAs) between primary OS and normal controls as well as pulmonary metastatic and primary OS were identified. A total of 65 DEmiRNAs, 233 DElncRNAs, and 1405 DEmRNAs were obtained between primary OS and normal controls; 48 DEmiRNAs, 50 DElncRNAs, and 307 DEmRNAs were obtained between pulmonary metastatic and primary OS. Then, the target DEmRNAs and DElncRNAs regulated by the same DEmiRNAs were searched and the OS tumorigenesis-related and OS pulmonary metastasis-related competing endogenous RNA (ceRNA) networks were constructed, respectively. Based on these ceRNA networks and Venn diagram analysis, we obtained 3 DEmiRNAs, 15 DElncRNAs, and 100 DEmRNAs, and eight target pairs including miR-223-5p/(CLSTN2, AC009951.1, LINC01705, AC090673.1), miR-378b/(ALX4, IGSF3, SULF1), and miR-323b-3p/TGFBR3 were involved in both tumorigenesis and pulmonary metastasis of OS. The TGF-β superfamily co-receptor TGFBR3, which is regulated by miR-323b-3p, acts as a tumor suppressor in OS tumorigenesis and acts as a tumor promoter in pulmonary metastatic OS via activation of the epithelial–mesenchymal transition (EMT) program.In conclusion, the OS transcriptome (miRNA, lncRNA, and mRNA) is dynamically regulated. These analyses might provide new clues to uncover the molecular mechanisms and signaling networks that contribute to OS progression, toward patient-tailored and novel-targeted treatments.
Phenotypic screening identifies a new oxazolone inhibitor of necroptosis and neuroinflammation
Authors: Oliveira Sara R. , Dionísio Pedro A. , Brito Hugo , Franco Lídia , Rodrigues Catarina A. B. , Guedes Rita C. , Afonso Carlos A. M. , Amaral Joana D. , Rodrigues Cecília M. P. 
Published: July 2018

AbstractNecroptosis is a regulated form of necrosis, which may be critical in the pathogenesis of neurodegenerative diseases. Neuroinflammation, characterized by the activation of glial cells such as microglia, is closely linked with neurodegenerative pathways and constitutes a major mechanism of neural damage and disease progression. Importantly, inhibition of necroptosis results in disease improvement, unveiling an alternative approach for therapeutic intervention. In the present study, we screened a small library of new molecules, potentially inhibitors of necroptosis, using two cellular models of necroptosis. A new oxazolone, Oxa12, reduced tumour necrosis factor α (TNF-α)-induced necroptosis in mouse L929 fibrosarcoma cells. Notably, Oxa12 strongly inhibited zVAD-fmk-induced necroptosis in murine BV2 microglial cells. Moreover, Oxa12 blocked phosphorylation of mixed-lineage kinase domain-like protein (MLKL), and interfered with necrosome complex formation, indicating that Oxa12 targets components upstream of MLKL. In fact, in silico molecular docking studies revealed that Oxa12 is occupying a region similar to the 1-aminoisoquinoline type II kinase inhibitor inside the receptor-interacting protein 1 (RIP1) kinase domain. Finally, in microglial cells, Oxa12 attenuated zVAD-fmk- and lipopolysaccharide (LPS)-induced inflammatory processes, as revealed by a marked decrease of TNF-α and/or IL-1β expression. More specifically, Oxa12 negatively targeted c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways, as well as NF-κB activation. Overall, we identified a strong lead inhibitor of necroptosis that is also effective at reducing inflammation-associated events. Oxa12 is a promising candidate molecule for further development to target disease states dependent on RIP kinase activity.
Autophagic cell death participates in POMC-induced melanoma suppression
Authors: Wu Jian-Ching , Tsai Han-En , Liu Guei-Sheung , Wu Chieh-Shan , Tai Ming-Hong 
Published: July 2018

AbstractHypoxia in tumors is known to trigger the pro-survival pathways such as autophagy. Systemic proopiomelanocortin (POMC) gene therapy suppresses melanoma through apoptosis induction and neovascularization blockage. In this study, we investigated the crosstalk between autophagic and apoptotic signaling in POMC-mediated melanoma suppression. By histological and immunoblot analysis, it was shown that POMC-treated melanoma tissues exhibited the prominent LC3 immunostaining, which was correlated with reduced CD31-positive tumor vascularization. Such autophagy induction could be recapitulated in melanoma cells receiving POMC gene delivery and hypoxia-mimicking agent cobalt chloride (CoCl2). We then utilized the POMC-derived peptide α-MSH with CoCl2 to elicit the autophagy as well as apoptosis in cultured melanoma cells. To delineate the role of autophagy during cell death, application of autophagy-inducer rapamycin enhanced, whereas autophagy inhibitor 3-MA attenuated, the α-MSH-induced apoptosis in melanoma cells. Genetic silencing of ATG5, an autophagy regulator, by RNA interference perturbed the α-MSH-induced apoptosis in melanoma cells. Finally, it was delineated that α-MSH stimulated the HIF-1α signaling as well as the expression of BNIP3/BNIP3L, thereby promoting the autophagy and apoptosis in melanoma cells. Therefore, the present study unveiled a unique function of autophagy in promoting cell death during POMC-mediated melanoma suppression via α-MSH/HIF-1α/BNIP3/BNIP3L signaling pathway.
Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission
Authors: Tasaki Shinya , Suzuki Katsuya , Kassai Yoshiaki , Takeshita Masaru , Murota Atsuko , Kondo Yasushi , Ando Tatsuya , Nakayama Yusuke , Okuzono Yuumi , Takiguchi Maiko , Kurisu Rina , Miyazaki Takahiro , Yoshimoto Keiko , Yasuoka Hidekata , Yamaoka Kunihiro , Morita Rimpei , Yoshimura Akihiko , Toyoshiba Hiroyoshi , Takeuchi Tsutomu 
Published: July 2018

AbstractSustained clinical remission (CR) without drug treatment has not been achieved in patients with rheumatoid arthritis (RA). This implies a substantial difference between CR and the healthy state, but it has yet to be quantified. We report a longitudinal monitoring of the drug response at multi-omics levels in the peripheral blood of patients with RA. Our data reveal that drug treatments alter the molecular profile closer to that of HCs at the transcriptome, serum proteome, and immunophenotype level. Patient follow-up suggests that the molecular profile after drug treatments is associated with long-term stable CR. In addition, we identify molecular signatures that are resistant to drug treatments. These signatures are associated with RA independently of known disease severity indexes and are largely explained by the imbalance of neutrophils, monocytes, and lymphocytes. This high-dimensional phenotyping provides a quantitative measure of molecular remission and illustrates a multi-omics approach to understanding drug response.
Anterior cingulate cortex and its input to the basolateral amygdala control innate fear response
Authors: Jhang Jinho , Lee Hyoeun , Kang Min Soo , Lee Han-Sol , Park Hyungju , Han Jin-Hee 
Published: July 2018

AbstractPrefrontal brain areas are implicated in the control of fear behavior. However, how prefrontal circuits control fear response to innate threat is poorly understood. Here, we show that the anterior cingulate cortex (ACC) and its input to the basolateral nucleus of amygdala (BLA) contribute to innate fear response to a predator odor in mice. Optogenetic inactivation of the ACC enhances freezing response to fox urine without affecting conditioned freezing. Conversely, ACC stimulation robustly inhibits both innate and conditioned freezing. Circuit tracing and slice patch recordings demonstrate a monosynaptic glutamatergic connectivity of ACC-BLA but no or very sparse ACC input to the central amygdala. Finally, our optogenetic manipulations of the ACC-BLA projection suggest its inhibitory control of innate freezing response to predator odors. Together, our results reveal the role of the ACC and its projection to BLA in innate fear response to olfactory threat stimulus.
Intrinsically ionic conductive cellulose nanopapers applied as all solid dielectrics for low voltage organic transistors
Authors: Dai Shilei , Chu Yingli , Liu Dapeng , Cao Fei , Wu Xiaohan , Zhou Jiachen , Zhou Bilei , Chen Yantao , Huang Jia 
Published: July 2018

AbstractBiodegradability, low-voltage operation, and flexibility are important trends for the future organic electronics. High-capacitance dielectrics are essential for low-voltage organic field-effect transistors. Here we report the application of environmental-friendly cellulose nanopapers as high-capacitance dielectrics with intrinsic ionic conductivity. Different with the previously reported liquid/electrolyte-gated dielectrics, cellulose nanopapers can be applied as all-solid dielectrics without any liquid or gel. Organic field-effect transistors fabricated with cellulose nanopaper dielectrics exhibit good transistor performances under operation voltage below 2 V, and no discernible drain current change is observed when the device is under bending with radius down to 1 mm. Interesting properties of the cellulose nanopapers, such as ionic conductivity, ultra-smooth surface (~0.59 nm), high transparency (above 80%) and flexibility make them excellent candidates as high-capacitance dielectrics for flexible, transparent and low-voltage electronics.