bluuebunny/crossref_metadata_2025_split huggingface dataset:
Color Ratios of Subauroral (STEVE) Arcs
Authors: Mende S. B. , Turner C. 
Published: June 2019

AbstractPhotos of a spectacular optical phenomenon, nicknamed STEVE, show finely structured, purple‐colored, east‐west arcs spanning the sky. These purple Sub‐auroral Arc Emissions are associated with Sub‐Auroral Ion Drifts, often accompanied by separate green arcs frequently displaying magnetic field aligned rays suggesting charge particle excitation. Both types of these arcs and polar auroras appear in some photos. Splitting the images into red, green, and blue channels allowed comparison of color ratios of the three phenomena. Wavelength calibration of the camera verified that the dominant atmospheric auroral emissions, 630.0 nm O(1D), O(1S) 557.7 nm, and N2+1N bands, were cleanly separated in the red, green, and blue channels of the camera. In the absence of a spectrogram the ratios between the color channels were interpreted in terms of possible excitation mechanisms. The purple arcs contained an excess of blue, presumably N2+1N intensity. This excess production could be due to the excitation of N2+ ions that were ionized through charge exchange with O+. The green companion arcs appear to be purely green (557.7) with almost no blue and minimal red suggesting excitation by low‐energy electrons excitation at altitudes >100 and <150 km.
Constraints on Appalachian Orogenesis and Continental Rifting in the Southeastern United States From Wide‐Angle Seismic Data
Authors: Marzen Rachel E. , Shillington Donna J. , Lizarralde Daniel , Harder Steven H. 
Published: June 2019

AbstractThe Southeastern United States is an ideal location to understand the interactions between mountain building, rifting, and magmatism. Line 2 of the Suwannee suture and Georgia Rift basin refraction seismic experiment in eastern Georgia extends 420 km from the Inner Piedmont to the Georgia coast. We model crustal and upper mantle VP and upper crustal VS. The most dramatic model transition occurs at the Higgins‐Zietz magnetic boundary, north of which we observe higher upper crustal VP and VS and lower VP/VS. These observations support the interpretation of the Higgins‐Zietz boundary as the Alleghanian suture. North of this boundary, we observe a low‐velocity zone less than 2 km thick at ~5‐km depth, consistent with a layer of sheared metasedimentary rocks that forms the Appalachian detachment. To the southeast, we interpret synrift sediments and decreasing crustal thickness to represent crustal thinning associated with the South Georgia Rift Basin and subsequent continental breakup. The correspondence of the northern limit of thinning with the interpreted suture location suggests that the orogenic suture zone and/or the Gondwanan crust to the south of the suture helped localize subsequent extension. Lower crustal VP and VP/VS preclude volumetrically significant mafic magmatic addition during rifting or associated with the Central Atlantic Magmatic Province. Structures formed during orogenesis and/or extension appear to influence seismicity in Georgia today; earthquakes localize along a steeply dipping zone that coincides with the northern edge of the South Georgia Basin and the change in upper crustal velocities at the Higgins‐Zietz boundary.
A global multi-hazard risk analysis of road and railway infrastructure assets
Authors: Koks E. E. , Rozenberg J. , Zorn C. , Tariverdi M. , Vousdoukas M. , Fraser S. A. , Hall J. W. , Hallegatte S. 
Published: June 2019

AbstractTransport infrastructure is exposed to natural hazards all around the world. Here we present the first global estimates of multi-hazard exposure and risk to road and rail infrastructure. Results reveal that ~27% of all global road and railway assets are exposed to at least one hazard and ~7.5% of all assets are exposed to a 1/100 year flood event. Global Expected Annual Damages (EAD) due to direct damage to road and railway assets range from 3.1 to 22 billion US dollars, of which ~73% is caused by surface and river flooding. Global EAD are small relative to global GDP (~0.02%). However, in some countries EAD reach 0.5 to 1% of GDP annually, which is the same order of magnitude as national transport infrastructure budgets. A cost-benefit analysis suggests that increasing flood protection would have positive returns on ~60% of roads exposed to a 1/100 year flood event.
Coordination mode engineering in stacked-nanosheet metal–organic frameworks to enhance catalytic reactivity and structural robustness
Authors: Huang Chuanhui , Dong Juncai , Sun Weiming , Xue Zhenjie , Ma Jun , Zheng Lirong , Liu Cong , Li Xiao , Zhou Kang , Qiao Xuezhi , Song Qian , Ma Wende , Zhang Lan , Lin Zhenyu , Wang Tie 
Published: June 2019

AbstractOptimising the supported modes of atom or ion dispersal onto substrates, to synchronously integrate high reactivity and robust stability in catalytic conversion, is an important yet challenging area of research. Here, theoretical calculations first show that three-coordinated copper (Cu) sites have higher activity than four-, two- and one-coordinated sites. A site-selective etching method is then introduced to prepare a stacked-nanosheet metal–organic framework (MOF, CASFZU-1)-based catalyst with precisely controlled coordination number sites on its surface. The turnover frequency value of CASFZU-1 with three-coordinated Cu sites, for cycloaddition reaction of CO2 with epoxides, greatly exceed those of other catalysts reported to date. Five successive catalytic cycles reveal the superior stability of CASFZU-1 in the stacked-nanosheet structure. This study could form a basis for the rational design and construction of highly efficient and robust catalysts in the field of single-atom or ion catalysis.
m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade
Authors: Yang Seungwon , Wei Jiangbo , Cui Yan-Hong , Park Gayoung , Shah Palak , Deng Yu , Aplin Andrew E. , Lu Zhike , Hwang Seungmin , He Chuan , He Yu-Ying 
Published: June 2019

AbstractMelanoma is one of the most deadly and therapy-resistant cancers. Here we show that N6-methyladenosine (m6A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma (IFNγ) and sensitizes melanoma to anti-PD-1 treatment in mice, depending on adaptive immunity. Our findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade may reduce the resistance to immunotherapy in melanoma.
Mechanisms of Ca2+/calmodulin-dependent kinase II activation in single dendritic spines
Authors: Chang Jui-Yun , Nakahata Yoshihisa , Hayano Yuki , Yasuda Ryohei 
Published: June 2019

AbstractCaMKIIα plays an essential role in decoding Ca2+ signaling in spines by acting as a leaky Ca2+ integrator with the time constant of several seconds. However, the mechanism by which CaMKIIα integrates Ca2+ signals remains elusive. Here, we imaged CaMKIIα-CaM association in single dendritic spines using a new FRET sensor and two-photon fluorescence lifetime imaging. In response to a glutamate uncaging pulse, CaMKIIα-CaM association increases in ~0.1 s and decays over ~3 s. During repetitive glutamate uncaging, which induces spine structural plasticity, CaMKIIα-CaM association did not show further increase but sustained at a constant level. Since CaMKIIα activity integrates Ca2+ signals over ~10 s under this condition, the integration of Ca2+ signal by CaMKIIα during spine structural plasticity is largely due to Ca2+/CaM-independent, autonomous activity. Based on these results, we propose a simple kinetic model of CaMKIIα activation in dendritic spines.
Mimicking immune signatures of flavivirus infection with targeted adjuvants improves dengue subunit vaccine immunogenicity
Authors: Bidet Katell , Ho Victor , Chu Collins Wenhan , Naim Ahmad Nazri Mohamed , Thazin Khaing , Chan Kuan Rong , Low Jenny G. H. , Choy Milly M. , Wong Lan Hiong , Florez de Sessions Paola , Lee Yie Hou , Hibberd Martin L. , Ooi Eng Eong , Fink Katja , Chen Jianzhu 
Published: June 2019

AbstractNeutralizing antibodies (nAbs) are a critical component for protection against dengue virus (DENV) infection, but little is known about the immune mechanisms governing their induction and whether such mechanisms can be harnessed for vaccine development. In this study, we profiled the early immune responses to flaviviruses in human peripheral blood mononuclear cells and screened a panel of toll-like receptor (TLR) agonists that stimulate the same immune signatures. Monocyte/macrophage-driven inflammatory responses and interferon responses were characteristics of flavivirus infection and associated with induction of nAbs in humans immunized with the yellow fever vaccine YF-17D. The signatures were best reproduced by the combination of TLR agonists Pam3CSK4 and PolyI:C (PP). Immunization of both mice and macaques with a poorly immunogenic recombinant DENV-2 envelope domain III (EDIII) induced more consistent nAb and CD4+ T-cell responses with PP compared to alum plus monophosphoryl lipid A. Induction of nAbs by PP required interferon-mediated signals in macrophages in mice. However, EDIII + PP vaccination only provided partial protection against viral challenge. These results provide insights into mechanisms underlying nAb induction and a basis for further improving antigen/adjuvant combinations for dengue vaccine development.
Neural and behavioral signature of human social perception
Authors: Saitovitch Ana , Lemaitre Hervé , Rechtman Elza , Vinçon-Leite Alice , Calmon Raphael , Grévent David , Dangouloff-Ros Volodia , Brunelle Francis , Boddaert Nathalie , Zilbovicius Monica 
Published: June 2019

AbstractSocial behavior is extremely variable among individuals, and the neural basis of this variability is still poorly understood. In this study, we aimed to investigate the neural basis of interindividual variability in the first step of social behavior, that is, social perception. For that purpose, we first used eye-tracking to measure social perception during the passive visualization of socially relevant movie clips. Second, we correlated eye-tracking data with measures of rest cerebral blood flow (CBF) obtained using arterial spin-labeling (ASL) MRI, an index of local rest brain function. The results showed a large interindividual variability in the number of fixations to the eyes of characters during passive visualization of movie clips displaying social interactions. Moreover, individual patterns remained stable across time, suggesting an individual signature of social behavior. Whole-brain analyses showed significant positive correlation between the number of fixations to the eyes and rest CBF: individuals who looked more to the eyes were those with higher rest CBF levels within the right superior temporal regions. Our results indicate the existence of a neural and behavioral signature associated with the interindividual variability in social perception.
Auditory metabolomics, an approach to identify acute molecular effects of noise trauma
Authors: Ji Lingchao , Lee Ho-Joon , Wan Guoqiang , Wang Guo-Peng , Zhang Li , Sajjakulnukit Peter , Schacht Jochen , Lyssiotis Costas A. , Corfas Gabriel 
Published: June 2019

AbstractAnimal-based studies have provided important insights into the structural and functional consequences of noise exposure on the cochlea. Yet, less is known about the molecular mechanisms by which noise induces cochlear damage, particularly at relatively low exposure levels. While there is ample evidence that noise exposure leads to changes in inner ear metabolism, the specific effects of noise exposure on the cochlear metabolome are poorly understood. In this study we applied liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS)-based metabolomics to analyze the effects of noise on the mouse inner ear. Mice were exposed to noise that induces temporary threshold shifts, synaptopathy and permanent hidden hearing loss. Inner ears were harvested immediately after exposure and analyzed by targeted metabolomics for the relative abundance of 220 metabolites across the major metabolic pathways in central carbon metabolism. We identified 40 metabolites differentially affected by noise. Our approach detected novel noise-modulated metabolites and pathways, as well as some already linked to noise exposure or cochlear function such as neurotransmission and oxidative stress. Furthermore, it showed that metabolic effects of noise on the inner ear depend on the intensity and duration of exposure. Collectively, our results illustrate that metabolomics provides a powerful approach for the characterization of inner ear metabolites affected by auditory trauma. This type of information could lead to the identification of drug targets and novel therapies for noise-induced hearing loss.
Genome-wide analysis of genetic variations between dominant and recessive NILs of glanded and glandless cottons
Authors: Zhao Tianlun , Li Cheng , Li Cong , Zhang Fan , Mei Lei , Chindudzi Elmon , Chen Jinhong , Zhu Shuijin 
Published: June 2019

AbstractCotton is an important economic crop in worldwide. It produces fiber for the textile industry and provides cottonseeds with high-quality protein and oil. However, the presence of gossypol limits the utilization of cottonseed. Two pairs of cotton near isogenic lines (NILs) with different pigment glands, i.e., Coker 312 vs Coker 312 W and CCRI12 vs CCRI12W, exhibit different gossypol contents. The glandless traits of Coker 312 W and CCRI12W are controlled by recessive and dominant genes, respectively. However, knowledge regarding the genomic variations in the NILs is limited. Therefore, the NILs genomes were resequenced and the sequencing depths were greater than 34×. Compared with the TM-1 genome, numerous SNPs, Indels, SVs, and CNVs were discovered. KEGG pathway analysis revealed that genes with SNPs and Indels from the recessive NILs and genes with Indels from the dominant NILs shared only one enriched pathway, i.e., the sesquiterpenoid and triterpenoid biosynthesis pathway, which is relevant to gossypol biosynthesis. Expression analysis revealed that key genes with variations that participate in the gossypol biosynthesis and pigment gland formation pathways had different expression patterns among the dominant, recessive glandless and glanded plants. The expression levels in the glanded organs were higher than those in their NILs. Altogether, our results provide deeper insight into cotton NILs with different pigment glands.
Counterconditioning following memory retrieval diminishes the reinstatement of appetitive memories in humans
Authors: Gera Rani , Barak Segev , Schonberg Tom 
Published: June 2019

AbstractAppetitive memories play a crucial role in learning and behavior, but under certain circumstances, such memories become maladaptive and play a vital role in addiction and other psychopathologies. Recent scientific research has demonstrated that memories can be modified following their reactivation through memory retrieval in a process termed memory reconsolidation. Several nonpharmacological behavioral manipulations yielded mixed results in their capacity to alter maladaptive memories in humans. Here, we aimed to translate the promising findings observed in rodents to humans. We constructed a novel three-day procedure using aversive counterconditioning to alter appetitive memories after short memory retrieval. On the first day, we used appetitive conditioning to form appetitive memories. On the second day, we retrieved these appetitive memories in one group (Retrieval group) but not in a second group. Subsequently, all participants underwent counterconditioning. On the third day, we attempted to reinstate the appetitive memories from day one. We observed a significant reduction in the reinstatement of the original appetitive memory when counterconditioning was induced following memory retrieval. Here, we provide a novel human paradigm that models several memory processes and demonstrate memory attenuation when counterconditioned after its retrieval. This paradigm can be used to study complex appetitive memory dynamics, e.g., memory reconsolidation and its underlying brain mechanisms.
miR-20a suppresses chondrogenic differentiation of ATDC5 cells by regulating Atg7
Authors: Xu Rui , Wei Yuhao , Yin Xing , Shi Bing , Li Jingtao 
Published: June 2019

AbstractBoth the miR-17-92 cluster and autophagy have been suggested as critical regulators of bone development, but the potential correlation between the two factors is largely unknown. Hence, we investigated whether members of this cluster can regulate chondrogenesis through an autophagy-related signalling pathway. In this study, the expression of miR-17-92 cluster members and the level of autophagic activity were investigated during chondrogenic induction in ATDC5 cells. miR-17, miR-18a, miR-20a, and miR-92-1 showed significant changes, and the level of autophagic activity was enhanced. Among the miR-17-92 cluster members, miR-20a showed the most significant change. Histological, cellular and molecular analyses were performed after the regulation of miR-20a and autophagy. miR-20a and autophagy had the opposite effect on chondrogenic differentiation, and there was a negative correlation between them. Moreover, the expression of the autophagy regulatory gene Atg7 was inhibited by miR-20a. siRNA was then used to knock down Atg7, and the results further indicated that Atg7 might be a potential target of miR-20a in chondrogenic differentiation. In conclusion, miR-20a is a critical negative regulator of chondrogenic differentiation because it inhibits autophagy via Atg7. Other members of the miR-17-92 cluster may have a similar effect, but this hypothesis requires further investigation.
Reprogramming Escherichia coli for the production of prenylated indole diketopiperazine alkaloids
Authors: Dubois Pavlina , Correia Isabelle , Le Chevalier Fabien , Dubois Steven , Jacques Isabelle , Canu Nicolas , Moutiez Mireille , Thai Robert , Gondry Muriel , Lequin Olivier , Belin Pascal 
Published: June 2019

AbstractPrenylated indole diketopiperazine (DKP) alkaloids are important bioactive molecules or their precursors. In the context of synthetic biology, efficient means for their biological production would increase their chemical diversification and the discovery of novel bioactive compounds. Here, we prove the suitability of the Escherichia coli chassis for the production of prenylated indole DKP alkaloids. We used enzyme combinations not found in nature by co-expressing bacterial cyclodipeptide synthases (CDPSs) that assemble the DKP ring and fungal prenyltransferases (PTs) that transfer the allylic moiety from the dimethylallyl diphosphate (DMAPP) to the indole ring of tryptophanyl-containing cyclodipeptides. Of the 11 tested combinations, seven resulted in the production of eight different prenylated indole DKP alkaloids as determined by LC-MS/MS and NMR characterization. Two were previously undescribed. Engineering E. coli by introducing a hybrid mevalonate pathway for increasing intracellular DMAPP levels improved prenylated indole DKP alkaloid production. Purified product yields of 2–26 mg/L per culture were obtained from culture supernatants. Our study paves the way for the bioproduction of novel prenylated indole DKP alkaloids in a tractable chassis that can exploit the cyclodipeptide diversity achievable with CDPSs and the numerous described PT activities.
Terpene Synthase Genes Originated from Bacteria through Horizontal Gene Transfer Contribute to Terpenoid Diversity in Fungi
Authors: Jia Qidong , Chen Xinlu , Köllner Tobias G. , Rinkel Jan , Fu Jianyu , Labbé Jessy , Xiong Wangdan , Dickschat Jeroen S. , Gershenzon Jonathan , Chen Feng 
Published: June 2019

AbstractFungi are successful eukaryotes of wide distribution. They are known as rich producers of secondary metabolites, especially terpenoids, which are important for fungi-environment interactions. Horizontal gene transfer (HGT) is an important mechanism contributing to genetic innovation of fungi. However, it remains unclear whether HGT has played a role in creating the enormous chemical diversity of fungal terpenoids. Here we report that fungi have acquired terpene synthase genes (TPSs), which encode pivotal enzymes for terpenoid biosynthesis, from bacteria through HGT. Phylogenetic analysis placed the majority of fungal and bacterial TPS genes from diverse taxa into two clades, indicating ancient divergence. Nested in the bacterial TPS clade is a number of fungal TPS genes that are inferred as the outcome of HGT. These include a monophyletic clade of nine fungal TPS genes, designated as BTPSL for bacterial TPS-like genes, from eight species of related entomopathogenic fungi, including seven TPSs from six species in the genus Metarhizium. In vitro enzyme assays demonstrate that all seven BTPSL genes from the genus Metarhizium encode active enzymes with sesquiterpene synthase activities of two general product profiles. By analyzing the catalytic activity of two resurrected ancestral BTPSLs and one closely related bacterial TPS, the trajectory of functional evolution of BTPSLs after HGT from bacteria to fungi and functional divergence within Metarhizium could be traced. Using M. brunneum as a model species, both BTPSLs and typical fungal TPSs were demonstrated to be involved in the in vivo production of terpenoids, illustrating the general importance of HGT of TPS genes from bacteria as a mechanism contributing to terpenoid diversity in fungi.
CD163+ immune cell infiltrates and presence of CD54+ microvessels are prognostic markers for patients with embryonal rhabdomyosarcoma
Authors: Kather Jakob Nikolas , Hörner Christian , Weis Cleo-Aron , Aung Thiha , Vokuhl Christian , Weiss Christel , Scheer Monika , Marx Alexander , Simon-Keller Katja 
Published: June 2019

AbstractRhabdomyosarcomas (RMS) are rare and often lethal diseases. It is assumed that the tumor microenvironment (TME) of RMS exerts an immunosuppressive function, but there is currently no systematic analysis of the immune cells infiltrating sarcoma tissue. Focusing on two common types of RMS (alveolar [RMA] and embryonal [RME]), we performed a comprehensive immunohistochemical analysis of tumor-infiltrating immune cells in the TME. We performed a qualitative estimation of infiltrating immune cells in the tumor microenvironment by an experienced pathologist as well as a quantitative digital pathology analysis. We found that (1) manual and automatic quantification of tumor-infiltrating immune cells were consistent; (2) RME tumors showed a higher degree of immune cell infiltration than RMA tumors but (3) the number of tumor infiltrating lymphocytes was low compared to other solid tumor types; (4) microvascular density correlated with immune cell infiltration and (5) CD163 positive macrophages as well as CD54 positive microvessels were more often detected in RME than in RMA and correlated with patient overall and event free survival. Our systematic analysis provides a comprehensive view of the immune landscape of RMS which needs to be taken into account for developing immunotherapies for this rare type of cancer.