bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Atmospheric CO2, CH4, and CO at Two Stations in the Tibetan Plateau of China
Authors: Guo Minrui , Fang Shuangxi , Liu Shuo , Liang Miao , Wu Hao , Yang Lulin , Li Zou , Liu Peng , Zhang Fang
Published: April 2020

The research of greenhouse gases on the Tibetan Plateau is of great importance since its unique topography as the third pole of our planet and profound response on the climate change. In this study, we compared the concurrent observations of atmospheric carbon dioxide (CO2), methane (CH4), and carbon monoxide (CO) during 2010–2016 from two stations located on the Tibetan Plateau, which are Mt. Waliguan station (WLG), the only World Meteorological Organization/Global Atmosphere Watch global station in the inland of Eurasia, and Shangri‐La station, a Chinese national station (XGLL). Although both stations are located at remote area, the atmospheric CO2, CH4, and CO concentrations are frequently influenced by regional sources, especially for XGLL throughout the year and WLG in summer. Due to the unique topography and regional conditions, the atmospheric CH4 and CO at both stations display different trends with other sites in China, with higher values in summer. The atmospheric CO2, CH4, and CO at the XGLL mainly represent the conditions in regional scale. As the only World Meteorological Organization/Global Atmosphere Watch global station in the inland of Eurasia, the observation results at WLG can be used to represent the conditions on the Tibetan Plateau, but some of them are frequently influenced by the emissions from the cities located on the east or north east, and some even can be affect by emissions from the Ganges basin in autumn and winter, which should be treated with caution. By subtracting the influences of the cities, we updated the growth rate of 2.45 ± 0.02 ppm yr−1 for CO2, 8.2 ± 0.1 ppb yr−1 for CH4, and −0.4 ± 0.1 ppb yr−1 for CO, compared to the prior estimation of 2.31 ± 0.02 ppm yr−1 for CO2, 8.1 ± 0.1 ppb yr−1 for CH4, and −0.6 ± 0.1 ppb yr−1 for CO on the Tibetan Plateau.
Observations of the Source Region of Whistler Mode Waves in Magnetosheath Mirror Structures
Authors: Kitamura N. , Omura Y. , Nakamura S. , Amano T. , Boardsen S. A. , Ahmadi N. , Le Contel O. , Lindqvist P.‐A. , Ergun R. E. , Saito Y. , Yokota S. , Gershman D. J. , Paterson W. R. , Pollock C. J. , Giles B. L. , Russell C. T. , Strangeway R. J. , Burch J. L.
Published: April 2020

In the magnetosheath, intense whistler mode waves, called “Lion roars,” are often detected in troughs of magnetic field intensity in mirror mode structures. Using data obtained by the four Magnetospheric Multiscale (MMS) spacecraft, we show that reversals of gradient of magnetic field intensity along the magnetic field correspond to reversals of the field‐aligned component of Poynting flux of whistler mode waves in the troughs. Such a characteristic is consistent with the idea that the whistler mode waves are effectively generated near the local minima of magnetic field intensity because of the smallest cyclotron resonance velocity and propagate toward regions of larger magnetic field intensity along the magnetic field lines on both sides. We use the reversal of the Poynting flux as an indicator of wave source regions. In these regions, we find that pancake or an outer edge of butterfly electron distributions above ~100 eV are good candidates for wave generation. Unclear correlations of phase difference and amplitude variations of whistler mode waves in cases of ~40 km spacecraft separation indicate that a simple plane wave approximation with a constant amplitude is not valid at this spatial scale that is much smaller than the ion gyroradius. The whistler mode waves consist of small coherent wave packets from multiple sources with spatial scales smaller than tens of electron gyroradii transverse to the background magnetic field in a mirror mode structure.
Calculating Effective Elastic Properties of Berea Sandstone Using the Segmentation‐Less Method Without Targets
Authors: Ikeda Ken , Goldfarb Eric J. , Tisato Nicola
Published: April 2020

We propose a new method to compute elastic properties of rocks from computed tomography (CT) images. A CT volume captures X‐ray attenuation, which is scaled in a CT number unit. Our method improves an existing segmentation‐less method where the CT volume is directly converted to elastic property arrays without using segmentation. A drawback of the existing segmentation‐less method is that it typically requires to scan physical targets of known density along with the sample. Targets map a CT volume into petrophysical property arrays by comparing the CT numbers of the sample with those of the targets. We introduce a segmentation‐less workflow that no longer requires targets but uses pseudotargets that are defined within the sample. Pseudotargets are composed of extrema CT numbers in the CT volume. We assume that regions containing extrema CT numbers represent pristine materials. The average CT numbers of such regions are paired to the pseudotarget densities to create a CT number‐to‐density conversion function. After density‐to‐porosity and porosity‐to‐elastic properties conversion, we simulate wave propagation on two Berea sandstone cores to estimate effective P and S wave velocities. To assess uncertainty, computed velocities are compared to laboratory measurements. We benchmark our technique against a segmentation‐less method, as well as the more commonly used segmentation‐based method. Among the three methods, the segmentation‐less method without targets yields the least absolute velocity error of 4.5%, whereas segmentation and segmentation‐less method yield +29% and +4.7% error, respectively. We conclude that the segmentation‐less method without targets can efficiently compute elastic properties of rocks from CT volumes, serving as a technique to create better subsurface models.
Atmospheric Dust Deposition Varies by Season and Elevation in the Colorado Front Range, USA
Authors: Heindel R. C. , Putman A. L. , Murphy S. F. , Repert D. A. , Hinckley E.‐L. S.
Published: April 2020

As atmospheric dust deposition continues to increase across the southwestern United States, it has the potential to alter ecosystem productivity and structure by delivering nutrients, base cations, and pollutants to remote mountain sites. Due to the sparse distribution of dust monitoring sites, open questions remain about the spatial and temporal variability of dust fluxes and composition across mountainous terrain. We present a 1 year (November 2017 to November 2018) record of seasonal dust fluxes and composition from an elevation transect across the Colorado Front Range extending from the urban plains to the remote alpine. At all nine sites, dust was enriched in the essential nutrient phosphorus and the metals copper, zinc, lead, and cadmium, elements that are enriched in dust deposited at sites across the Rocky Mountain West. We observed a seasonal pattern in dust composition, with the highest concentrations of zinc and cadmium during the summer, when back trajectory modeling suggested a greater contribution of dust from local urban and agricultural regions to the east of the collection sites. During the summer, there was also a trend of higher dust fluxes at lower elevations; dust fluxes ranged from 18.9 ± 0.1 g m−2 yr−1 on the plains to 5.9 ± 0.2 g m−2 yr−1 in the alpine. Our results suggest that urban and agricultural land east of the Colorado Front Range is an important source of nutrients and pollutants to all elevations of the mountain range.
Detrital Thermochronometry Reveals That the Topography Along the Antarctic Peninsula is Not a Pleistocene Landscape
Authors: Clinger Anna E. , Fox Matthew , Balco Greg , Cuffey Kurt , Shuster David L.
Published: April 2020

Using offshore detrital apatite (U‐Th)/He thermochronometry and 3D thermo‐kinematic modeling of the catchment topography, we constrain the timing of major topographic change at Bourgeois Fjord, Antarctic Peninsula (AP). While many mid‐latitude glacial landscapes developed primarily in response to global cooling over the last ~2.6 Ma, we find that kilometer‐scale landscape evolution at Bourgeois Fjord began ~30–12 Ma ago and <2 km of valley incision has occurred since ~16 Ma. This early onset of major topographic change occurred following the initiation of alpine glaciation at this location and prior to the development of a regional polythermal ice sheet inferred from sedimentary evidence offshore of the AP. We hypothesize that topographic change relates to (i) feedbacks between an evolving topography and glacial erosion processes, (ii) effects of glacial‐interglacial variability, and (iii) the prevalence of subglacial meltwater. The timing and inferred spatial patterns of long‐term exhumation at Bourgeois Fjord are consistent with a hypothesis that glacial erosion processes were suppressed at the AP during global Plio‐Pleistocene cooling, rather than enhanced. Our study examines the long‐term consequences of glacial processes on catchment‐wide erosion as the local climate cooled. Our findings support the hypothesis that landscapes at different latitudes had different responses to global cooling. Our results also suggest that erosion is enhanced along the plateau flanks of Bourgeois Fjord today, which may be due to periglacial processes or mantling via subglacial till. If regional warming persists and meltwater becomes more pronounced, we predict that enhanced erosion along the plateau flank will accelerate topographic change.
Evaluation of Spatio‐Temporal Characteristics of Different Zenith Tropospheric Delay Models in Antarctica
Authors: Li Fei , Zhang Qingchuan , Zhang Shengkai , Lei Jintao , Li Wenhao
Published: April 2020

Zenith tropospheric delay (ZTD) is one of the main error sources in space geodetic techniques, such as Global Positioning System (GPS) and satellite altimetry. To qualitatively and quantitatively determine the most suitable model for Antarctica, we analyze the accuracy and applicability of nine models (UNB3m, EGNOS, GPT2 + Saastamoinen, GPT2w + Saastamoinen, GPT3 + Saastamoinen, GPT2 + Hopfield, GPT2w + Hopfield, GPT3 + Hopfield, and IGGtropSH) in Antarctica using 8 years of GPS‐derived ZTD time series from 65 stations. The results show that the GPT2/2w/3 + SAAS models are better than the other six models, with a bias of 0.2, −0.22, and −0.29 cm and root mean square (RMS) of 2.33, 2.31, and 2.36 cm. Based on the decimeter bias and RMS, the UNB3m model and EGNOS model present the worst performance in Antarctica. There are regional characteristics of bias and RMS in the nine models. The GPT2/2w/3 + SAAS models have the smallest regional deviation, and the bias and RMS between subregions (Antarctic Peninsula, Amundsen Sea Embayment, Ross Ice Shelf, Inland area of West Antarctica, Filchner‐Ronne Ice Shelf, and coastal East Antarctica) are all at the 0.2 and 0.7 cm levels, respectively. The GPT2/2w/3 + HOP models have the largest regional deviation, with regional bias and RMS at the levels of 8 and 6 cm, respectively. Our results suggest that the uncertainty of ice sheet elevation derived from satellite altimetry may be partly caused by the spatial‐related bias and error in the ZTD corrections. The bias and RMS of six GPT combined models and the IGGtropSH model present limited seasonal changes, indicating that these models can simulate the seasonal characteristics of ZTD better. The time series of the bias and RMS values of the EGNOS and UNB3m models show obvious seasonal characteristics, which may contaminate the annual ice sheet elevation by approximately 5 cm if used as ZTD corrections.
Integrating Water Management Instruments to Reconcile a Hydro‐Economic Water Allocation Strategy With Other Water Preferences
Authors: Dalcin Ana Paula , Fernandes Marques Guilherme
Published: April 2020

Increasing scarcity and pollution has called for changes in water policies, which should reflect society's preferences toward water use, development, and the environment. Water management is still limited in incorporating changing policies and in deriving directives to implement water instruments under long‐term planning. Some examples are water charges that do not reflect watershed externalities and water permits lacking future vision of allocation. Hydro‐economic modeling has explored trade‐offs of water allocation and improved water operations but still does not address instruments' integration. This paper proposes a modeling approach that identifies how to apply water management instruments integrated with each other to deliver a water allocation strategy reconciled with economic development projections and changing water use preferences. This improves our understanding on adjusting the implementation of water management instruments considering future outcomes and trade‐offs. The methodology combines discrete dynamic programming to determine increments in water permits, multiobjective linear programming to generate a Pareto set to model users' water preferences, and nonlinear programming to allocate water permits over different river reaches subject to water quality targets. The reconciliation allowed to identify sustainable water allocation strategies supported by a watershed, and instruments' integration to make it feasible. Strategies imposing limited water permits to economic users and watershed regions indicated where (and when) water conservation programs should be applied, along with quantitative targets (how much). The economic trade‐offs identified reference values for economic instruments to compensate the externalities. Finally, less strict water quality targets did not result in higher economic returns.
Measuring and Modeling Gravel Transport at Caspar Creek, CA, to Detect Changes in Sediment Supply, Storage, and Transport Efficiency
Authors: Richardson P. W. , Wagenbrenner J. W. , Sutherland D. G. , Lisle T. E.
Published: April 2020

We developed a technique for reconstructing annual gravel yields and generated a 55‐year record of gravel transport for the North Fork catchment of the Caspar Creek Experimental Watersheds in Northern California. The technique relies on field data collection including annual surveys of weir pond volumes and suspended sediment measurements, as well as an accounting for settling of suspended sediment and organic matter in the pond. We compared these annual yields to gravel yields predicted by the Wilcock two‐fraction bed load transport model, which we calibrated from measured values at Caspar Creek. We considered three velocity‐discharge relationships and found that values of hydraulic variables measured during storms produced the best fit between reconstructed and predicted annual gravel yields when years with large disturbances were excluded. We also compared predicted gravel transport rates to bed load transport rates measured from 1988 to 1995 with bed load pit samplers. We found that the calibrated model predictions agreed well with the field‐measured bed load transport rates. To investigate the role of supply and storage on gravel transport, we compared the reconstructed gravel yields to predicted gravel yields and found that increased occurrence of landslides and headcut erosion in the 1990s and early 2000s did not lead to an increase in gravel yields. Instead, input of large downed wood in the 1990s created storage space and decreased bed load delivery to the weir pond.
Preferential Flow Enhances Pumping‐Induced Saltwater Intrusion in Volcanic Aquifers
Authors: Geng Xiaolong , Michael Holly A.
Published: April 2020

Preferential flow can result in rapid contamination of groundwater resources. This is particularly true in aquifers with connected, high permeability geologic structures and in coastal systems where the oceanic source of contamination is ubiquitous. We consider saltwater intrusion due to pumping in volcanic aquifers with lava tubes represented as connected high‐K structures and compare salinization responses to those of heterogeneous aquifers with different structure and equivalent homogeneous systems. Three‐dimensional simulations of variable‐density groundwater flow and salt transport show that conduits formed by lava flows create preferential groundwater flow in volcanic aquifers. These conduits allow fresh groundwater to extend further offshore than in other systems. However, onshore pumping causes saltwater to migrate landward quickly through the conduits relative to the other models, resulting in more severe saltwater intrusion, particularly at shallow depths. The geometry of geologic heterogeneity in volcanic aquifers leads to increased risk of salinization of fresh groundwater as well as substantial uncertainty due to significant spatial variation in saltwater intrusion. The findings illustrate the importance of considering geologic heterogeneity in assessing the vulnerability of coastal freshwater resources in volcanic and other aquifers with connected high‐permeability geologic structures.
Evaluation of Cloud Microphysical Properties Derived From MODIS and Himawari‐8 Using In Situ Aircraft Measurements Over the Southern Ocean
Authors: Zhao Lijun , Zhao Chuanfeng , Wang Yang , Wang Yuan , Yang Yikun
Published: April 2020

Cloud microphysical properties from aircraft measurements during the Southern Ocean Clouds, Radiation, Aerosol Transport Experimental Study are used to evaluate the cloud products from the geostationary satellite Himawari‐8 (H‐8) and the polar‐orbiting satellite the Moderate Resolution Imaging Spectroradiometer (MODIS). Compared to the in situ aircraft observations when aircraft flew horizontally near cloud tops, the cloud droplet effective radius (re) and number concentration (Nd) from H‐8 (MODIS) are 33% (26%–31%) and 2% (9–13%) larger. Both the H‐8 and MODIS retrievals behave similarly for liquid‐only and mixed‐phase low‐level clouds, indicating the weak sensitivity of the satellite cloud retrieval performance to cloud phase. The re and Nd of the cloud profiles from aircraft measurements were also used to compare with the satellite product. It shows that H‐8 re and Nd agree better with aircraft measurements when considering only the in situ data acquired in the upper portions (highest 20%) of the clouds. Roughly, the re overestimation by H‐8 decreases from 18% to 3% when considering the upper portions of clouds compared to all cloud layer averages, except for one case with drizzles appeared. In addition, the performance of MODIS re and Nd is highly dependent on the wavelengths the retrieval method uses. The droplet re retrievals using wavelength of 1.6 μm have much larger biases than that using the other two channels. The potential effects of the cloud vertical variation and the photon penetration depth, the cloud heterogeneity, the cloud droplet size spectra, and the drizzle on satellite retrievals have also been discussed.
Urban Heat Islands Are Warming the Arctic
Authors: Katz Cheryl
Published: April 2020

Even in the remote high latitudes, a new satellite study sees rising temperatures and spreading green belts around cities, with big impacts on soils and ecosystems.
Evidence Is Growing That Alternative Stable States in Semiarid Grasslands Are the Exception, Not the Rule
Authors: Kleinhesselink Andrew
Published: April 2020

Woody shrubs have increased in abundance in arid and semiarid grasslands around the globe. This can have negative consequences for communities dependent on grasses for grazing and other ecosystem services. A study by Zheng et al. (2020, https://doi.org/10.1029/2019JG005439) shows that grasslands in Inner Mongolia, China, which have long been invaded by shrubs, may naturally return to a grass‐dominated state when grazing is eliminated. This result emphasizes the primary importance of grazing in driving vegetation change in grasslands and argues against the existence of critical thresholds and alternative stable states in semiarid ecosystems.
Dysregulation of the EphrinB2−EphB4 ratio in pediatric cerebral arteriovenous malformations is associated with endothelial cell dysfunction in vitro and functions as a novel noninvasive biomarker in patients
Authors: Fehnel Katie Pricola , Penn David L. , Duggins-Warf Micah , Gruber Maxwell , Pineda Steven , Sesen Julie , Moses-Gardner Alexander , Shah Nishali , Driscoll Jessica , Zurakowski David , Orbach Darren B. , Smith Edward R.
Published: April 2020

We investigated (1) EphrinB2 and EphB4 receptor expression in cerebral AVMs, (2) the impact of an altered EphrinB2:EphB4 ratio on brain endothelial cell function and (3) potential translational applications of these data. The following parameters were compared between AVM endothelial cells (AVMECs) and human brain microvascular endothelial cells (HBMVECs): quantified EphrinB2 and EphB4 expression, angiogenic potential, and responses to manipulation of the EphrinB2:EphB4 ratio via pharmacologic stimulation/inhibition. To investigate the clinical relevance of these in vitro data, Ephrin expression was assessed in AVM tissue (by immunohistochemistry) and urine (by ELISA) from pediatric patients with AVM (n = 30), other cerebrovascular disease (n = 14) and control patients (n = 29), and the data were subjected to univariate and multivariate statistical analyses. Compared to HBMVECs, AVMECs demonstrated increased invasion (p = 0.04) and migration (p = 0.08), impaired tube formation (p = 0.06) and increased EphrinB2:EphB4 ratios. Altering the EphrinB2:EphB4 ratio (by increasing EphrinB2 or blocking EphB4) in HBMVECs increased invasion (p = 0.03 andp < 0.05, respectively). EphrinB2 expression was increased in AVM tissue, which correlated with increased urinary EphrinB2 levels in AVM patients. Using the optimal urinary cutoff value (EphrinB2 > 25.7 pg/μg), AVMs were detected with high accuracy (80% vs. controls) and were distinguished from other cerebrovascular disease (75% accuracy). Post-treatment urinary EphrinB2 levels normalized in an index patient. In summary, AVMECs have an EphrinB2:EphB4 ratio that is increased compared to that of normal HBMVECs. Changing this ratio in HBMVECs induces AVMEC-like behavior. EphrinB2 is clinically relevant, and its levels are increased in AVM tissue and patient urine. This work suggests that dysregulation of the EphrinB2:EphB4 signaling cascade and increases in EphrinB2 may play a role in AVM development, with potential utility as a diagnostic and therapeutic target.
Towards visible-wavelength passively mode-locked lasers in all-fibre format
Authors: Zou Jinhai , Dong Chuchu , Wang Hongjian , Du Tuanjie , Luo Zhengqian
Published: April 2020

Mode-locked fibre lasers (MLFLs) are fundamental building blocks of many photonic systems used in industrial, scientific and biomedical applications. To date, 1–2 μm MLFLs have been well developed; however, passively mode-locked fibre lasers in the visible region (380–760 nm) have never been reported. Here, we address this challenge by demonstrating an all-fibre visible-wavelength passively mode-locked picosecond laser at 635 nm. The 635 nm mode-locked laser with an all-fibre figure-eight cavity uses a Pr/Yb codoped ZBLAN fibre as the visible gain medium and a nonlinear amplifying loop mirror as the mode-locking element. First, we theoretically predict and analyse the formation and evolution of 635 nm mode-locked pulses in the dissipative soliton resonance (DSR) regime by solving the Ginzburg-Landau equation. Then, we experimentally demonstrate the stable generation of 635 nm DSR mode-locked pulses with a pulse duration as short as ~96 ps, a radio-frequency signal-to-noise ratio of 67 dB and a narrow spectral bandwidth of <0.1 nm. The experimental results are in excellent agreement with our numerical simulations. In addition, we also observe 635 nm noise-like pulse operation with a wide (>1 nm) and modulated optical spectrum. This work represents an important step towards miniaturized ultrafast fibre lasers in the visible spectral region.
Characterization of viruses in a tapeworm: phylogenetic position, vertical transmission, and transmission to the parasitized host
Authors: Hahn Megan A , Rosario Karyna , Lucas Pierrick , Dheilly Nolwenn M
Published: April 2020

Parasitic flatworms (Neodermata) infect all vertebrates and represent a significant health and economic burden worldwide due to the debilitating diseases they cause. This study sheds light for the first time into the virome of a tapeworm by describing six novel RNA virus candidate species associated with Schistocephalus solidus, including three negative-strand RNA viruses (order Jingchuvirales, Mononegavirales, and Bunyavirales) and three double-stranded RNA viruses. Using in vitro culture of S. solidus, controlled experimental infections and field sampling, we demonstrate that five of these viruses are vertically transmitted, and persist throughout the S. solidus complex life cycle. Moreover, we show that one of the viruses, named Schistocephalus solidus rhabdovirus (SsRV1), is excreted by the parasite and transmitted to parasitized hosts indicating that it may impact S. solidus–host interactions. In addition, SsRV1 has a basal phylogenetic position relative to vertebrate rhabdoviruses suggesting that parasitic flatworms could have contributed to virus emergence. Viruses similar to four of the S. solidus viruses identified here were found in geographically distant S. solidus populations through data mining. Further studies are necessary to determine if flatworm viruses can replicate in parasitized hosts, how they contribute to parasite infection dynamics and if these viruses could be targeted for treatment of parasitic disease.
Transcriptome signatures from discordant sibling pairs reveal changes in peripheral blood immune cell composition in Autism Spectrum Disorder
Authors: Filosi Michele , Kam-Thong Tony , Essioux Laurent , Muglia Pierandrea , Trabetti Elisabetta , Spooren Will , Müller-Myshok Bertram ,   Italian Autism Network, Alibrio Giovanni , Anchisi Laura , Andruccioli Milena , Benvenuto Arianna , Battistella Pier Antonio , Boscaini Flavio , Bravaccio Carmela , Ceppi Elisa , Cosentino Diego , Curatolo Paolo , Da Ros Lucio , Bernardina Bernardo Dalla , De Giacomo Andrea , Di Vita Giuseppa , Domenici Enrico , Elia Massimo , Gitti Filippo , Grittani Serenella , Lamanna Anna Linda , Mani Elisa , Manzi Barbara , Margari Lucia , Masi Gabriele , Molteni Massimo , Muglia Pierandrea , Nardocci Franco , Pascotto Antonio , Parmeggiani Antonia , Pignatti Pier Franco , Piroddi Tiziana , Prandini Paola , Ratti Emiliangelo , Rizzini Paolo , Russo Sebastiano , Scifo Renato , Tancredi Raffaella , Tiberti Alessandra , Trabetti Elisabetta , Zoccante Leonardo , Zuddas Alessandro , Domenici Enrico
Published: April 2020

Notwithstanding several research efforts in the past years, robust and replicable molecular signatures for autism spectrum disorders from peripheral blood remain elusive. The available literature on blood transcriptome in ASD suggests that through accurate experimental design it is possible to extract important information on the disease pathophysiology at the peripheral level. Here we exploit the availability of a resource for molecular biomarkers in ASD, the Italian Autism Network (ITAN) collection, for the investigation of transcriptomic signatures in ASD based on a discordant sibling pair design. Whole blood samples from 75 discordant sibling pairs selected from the ITAN network where submitted to RNASeq analysis and data analyzed by complementary approaches. Overall, differences in gene expression between affected and unaffected siblings were small. In order to assess the contribution of differences in the relative proportion of blood cells between discordant siblings, we have applied two different cell deconvolution algorithms, showing that the observed molecular signatures mainly reflect changes in peripheral blood immune cell composition, in particular NK cells. The results obtained by the cell deconvolution approach are supported by the analysis performed by WGCNA. Our report describes the largest differential gene expression profiling in peripheral blood of ASD subjects and controls conducted by RNASeq. The observed signatures are consistent with the hypothesis of immune alterations in autism and an increased risk of developing autism in subjects exposed to prenatal infections or stress. Our study also points to a potential role of NMUR1, HMGB3, and PTPRN2 in ASD.
IDH mutation in glioma: molecular mechanisms and potential therapeutic targets
Authors: Han Sue , Liu Yang , Cai Sabrina J. , Qian Mingyu , Ding Jianyi , Larion Mioara , Gilbert Mark R. , Yang Chunzhang
Published: April 2020

Isocitrate dehydrogenase (IDH) enzymes catalyse the oxidative decarboxylation of isocitrate and therefore play key roles in the Krebs cycle and cellular homoeostasis. Major advances in cancer genetics over the past decade have revealed that the genes encoding IDHs are frequently mutated in a variety of human malignancies, including gliomas, acute myeloid leukaemia, cholangiocarcinoma, chondrosarcoma and thyroid carcinoma. A series of seminal studies further elucidated the biological impact of the IDH mutation and uncovered the potential role of IDH mutants in oncogenesis. Notably, the neomorphic activity of the IDH mutants establishes distinctive patterns in cancer metabolism, epigenetic shift and therapy resistance. Novel molecular targeting approaches have been developed to improve the efficacy of therapeutics against IDH-mutated cancers. Here we provide an overview of the latest findings in IDH-mutated human malignancies, with a focus on glioma, discussing unique biological signatures and proceedings in translational research.
Identification of a novel tumor angiogenesis inhibitor targeting Shh/Gli1 signaling pathway in Non-small cell lung cancer
Authors: Lei Xueping , Zhong Yihang , Huang Lijuan , Li Songpei , Fu Jijun , Zhang Lingmin , Zhang Yu , Deng Qiudi , Yu Xiyong
Published: April 2020

Although angiogenesis inhibitors targeting VEGF/VEGFR2 have been applied for tumor therapy, the outcomes are still unsatisfactory. Thus, it is urgent to develop novel angiogenesis inhibitor for cancer therapy from new perspectives. Identification of novel angiogenesis inhibitor from natural products is believed to be one of most promising strategy. In this study, we showed that pristimerin, an active agent isolated from traditional Chinese herbal medicine Celastrus aculeatus Merr, was a novel tumor angiogenesis inhibitor that targeting sonic hedgehog (Shh)/glioma associated oncogene 1 (Gli1) signaling pathway in non-small cell lung cancer (NSCLC). We showed that pristimerin affected both the early- and late-stage of angiogenesis, suggesting by that pristimerin inhibited Shh-induced endothelial cells proliferation, migration, invasion as well as pericytes recruitment to the endothelial tubes, which is critical for the new blood vessel maturation. It also suppressed tube formation, vessel sprouts formation and neovascularization in chicken embryo chorioallantoic membrane (CAM). Moreover, it significantly decreased microvessel density (MVD) and pericyte coverage in NCI-H1299 xenografts, resulting in tumor growth inhibition. Further research revealed that pristimerin suppressed tumor angiogenesis by inhibiting the nucleus distribution of Gli1, leading to inactivation of Shh/Gli1 and its downstream signaling pathway. Taken together, our study showed that pristimerin was a promising novel anti-angiogenic agent for the NSCLC therapy and targeting Shh/Gli1 signaling pathway was an effective approach to suppress tumor angiogenesis.
Bacterial type III effector protein HopQ inhibits melanoma motility through autophagic degradation of vimentin
Authors: Park Seung-Ho , Yoon Sung-Jin , Choi Song , Kim Jun-Seob , Lee Moo-Seung , Lee Seon-Jin , Lee Sang-Hyun , Min Jeong-Ki , Son Mi-Young , Ryu Choong-Min , Yoo Jiyun , Park Young-Jun
Published: April 2020

Malignant melanoma is a fatal disease that rapidly spreads to the whole body. Treatments have limited efficiency owing to drug resistance and various side effects. Pseudomonas syringae pv. tomato (Pto) is a model bacterial pathogen capable of systemic infection in plants. Pto injects the effector protein HopQ into the plant cytosol via a type III secretion machinery and suppresses the host immunity. Intriguingly, host plant proteins regulated by HopQ are conserved even in humans and conferred in tumor metastasis. Nevertheless, the potential for HopQ to regulate human cancer metastasis was unknown. In this study, we addressed the suitability of HopQ as a possible drug against melanoma metastasis. In melanoma cells, overexpressed HopQ is phosphorylated and bound to 14-3-3 through its N-terminal domain, resulting in stronger interaction between HopQ and vimentin. The binding of HopQ to vimentin allowed for degradation of vimentin via p62-dependent selective autophagy. Attenuation of vimentin expression by HopQ inhibited melanoma motility and in vivo metastasis. These findings demonstrated that HopQ directly degraded vimentin in melanoma cells and could be applied to an inhibitor of melanoma metastasis.
Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction
Authors: Yin Mingzhu , Guo Ying , Hu Rui , Cai Wesley L. , Li Yao , Pei Shiyao , Sun Hongyin , Peng Cong , Li Jiali , Ye Rui , Yang Qiaohong , Wang Nenghui , Tao Yongguang , Chen Xiang , Yan Qin
Published: April 2020

Small molecule inhibitor of the bromodomain and extraterminal domain (BET) family proteins is a promising option for cancer treatment. However, current BET inhibitors are limited by their potency or oral bioavailability. Here we report the discovery and characterization of NHWD-870, a BET inhibitor that is more potent than three major clinical stage BET inhibitors BMS-986158, OTX-015, and GSK-525762. NHWD-870 causes tumor shrinkage or significantly suppresses tumor growth in nine xenograft or syngeneic models. In addition to its ability to downregulate c-MYC and directly inhibit tumor cell proliferation, NHWD-870 blocks the proliferation of tumor associated macrophages (TAMs) through multiple mechanisms, partly by reducing the expression and secretion of macrophage colony-stimulating factor CSF1 by tumor cells. NHWD-870 inhibits CSF1 expression through suppressing BRD4 and its target HIF1α. Taken together, these results reveal a mechanism by which BRD4 inhibition suppresses tumor growth, and support further development of NHWD-870 to treat solid tumors.
Imaging small molecule-induced endosomal escape of siRNA
Authors: Du Rietz Hampus , Hedlund Hampus , Wilhelmson Sten , Nordenfelt Pontus , Wittrup Anders
Published: April 2020

Small interfering RNAs (siRNAs) are a new class of promising therapeutic molecules that can be used for sequence-specific downregulation of disease-causing genes. However, endosomal entrapment of siRNA is a key hurdle for most delivery strategies, limiting the therapeutic effect. Here, we use live-cell microscopy and cytosolic galectin-9 as a sensor of membrane damage, to probe fundamental properties of endosomal escape of cholesterol-conjugated siRNA induced by endosome-disrupting compounds. We demonstrate efficient release of ligand-conjugated siRNA from vesicles damaged by small molecules, enhancing target knockdown up to ∼47-fold in tumor cells. Still, mismatch between siRNA-containing and drug-targeted endolysosomal compartments limits siRNA activity improvement. We also show widespread endosomal damage in macroscopic tumor spheroids after small molecule treatment, substantially improving siRNA delivery and knockdown throughout the spheroid. We believe the strategy to characterize endosomal escape presented here will be widely applicable, facilitating efforts to improve delivery of siRNA and other nucleic acid-based therapeutics.
Self-preservation strategy for approaching global warming targets in the post-Paris Agreement era
Authors: Wei Yi-Ming , Han Rong , Wang Ce , Yu Biying , Liang Qiao-Mei , Yuan Xiao-Chen , Chang Junjie , Zhao Qingyu , Liao Hua , Tang Baojun , Yan Jinyue , Cheng Lijing , Yang Zili
Published: April 2020

A strategy that informs on countries’ potential losses due to lack of climate action may facilitate global climate governance. Here, we quantify a distribution of mitigation effort whereby each country is economically better off than under current climate pledges. This effort-sharing optimizing approach applied to a 1.5 °C and 2 °C global warming threshold suggests self-preservation emissions trajectories to inform NDCs enhancement and long-term strategies. Results show that following the current emissions reduction efforts, the whole world would experience a washout of benefit, amounting to almost 126.68–616.12 trillion dollars until 2100 compared to 1.5 °C or well below 2 °C commensurate action. If countries are even unable to implement their current NDCs, the whole world would lose more benefit, almost 149.78–791.98 trillion dollars until 2100. On the contrary, all countries will be able to have a significant positive cumulative net income before 2100 if they follow the self-preservation strategy.
Drought alters the biogeochemistry of boreal stream networks
Authors: Gómez-Gener Lluís , Lupon Anna , Laudon Hjalmar , Sponseller Ryan A.
Published: April 2020

Drought is a global phenomenon, with widespread implications for freshwater ecosystems. While droughts receive much attention at lower latitudes, their effects on northern river networks remain unstudied. We combine a reach-scale manipulation experiment, observations during the extreme 2018 drought, and historical monitoring data to examine the impact of drought in northern boreal streams. Increased water residence time during drought promoted reductions in aerobic metabolism and increased concentrations of reduced solutes in both stream and hyporheic water. Likewise, data during the 2018 drought revealed widespread hypoxic conditions and shifts towards anaerobic metabolism, especially in headwaters. Finally, long-term data confirmed that past summer droughts have led to similar metabolic alterations. Our results highlight the potential for drought to promote biogeochemical shifts that trigger poor water quality conditions in boreal streams. Given projected increases in hydrological extremes at northern latitudes, the consequences of drought for the health of running waters warrant attention.
SciBet as a portable and fast single cell type identifier
Authors: Li Chenwei , Liu Baolin , Kang Boxi , Liu Zedao , Liu Yedan , Chen Changya , Ren Xianwen , Zhang Zemin
Published: April 2020

Fast, robust and technology-independent computational methods are needed for supervised cell type annotation of single-cell RNA sequencing data. We present SciBet, a supervised cell type identifier that accurately predicts cell identity for newly sequenced cells with order-of-magnitude speed advantage. We enable web client deployment of SciBet for rapid local computation without uploading local data to the server. Facing the exponential growth in the size of single cell RNA datasets, this user-friendly and cross-platform tool can be widely useful for single cell type identification.
Obesity-induced overexpression of miR-802 impairs insulin transcription and secretion
Authors: Zhang Fangfang , Ma Dongshen , Zhao Wanli , Wang Danwei , Liu Tingsheng , Liu Yuhong , Yang Yue , Liu Yue , Mu Jinming , Li Bingbing , Zhang Yanfeng , Pan Yi , Guo Changying , Du Hong , Li Ling , Fu Xianghui , Cao Zhengyu , Jin Liang
Published: April 2020

B cell dysfunction due to obesity can be associated with alterations in the levels of micro-RNAs (miRNAs). However, the role of miRNAs in these processes remains elusive. Here, we show that miR-802 is increased in the pancreatic islets of obese mouse models and demonstrate that inducible transgenic overexpression of miR-802 in mice causes impaired insulin transcription and secretion. We identify Foxo1 as a transcription factor of miR-802 promoting its transcription, and NeuroD1 and Fzd5 as targets of miR-802-dependent silencing. Repression of NeuroD1 in β cell and primary islets impairs insulin transcription and reduction of Fzd5 in β cell, which, in turn, impairs Ca2+ signaling, thereby repressing calcium influx and decreasing insulin secretion. We functionally create a novel network between obesity and β cell dysfunction via miR-802 regulation. Elucidation of the impact of obesity on microRNA expression can broaden our understanding of pathophysiological development of diabetes.
Elevated protein synthesis in microglia causes autism-like synaptic and behavioral aberrations
Authors: Xu Zhi-Xiang , Kim Gyu Hyun , Tan Ji-Wei , Riso Anna E. , Sun Ye , Xu Ethan Y. , Liao Guey-Ying , Xu Haifei , Lee Sang-Hoon , Do Na-Young , Lee Chan Hee , Clipperton-Allen Amy E. , Kwon Soonwook , Page Damon T. , Lee Kea Joo , Xu Baoji
Published: April 2020

Mutations that inactivate negative translation regulators cause autism spectrum disorders (ASD), which predominantly affect males and exhibit social interaction and communication deficits and repetitive behaviors. However, the cells that cause ASD through elevated protein synthesis resulting from these mutations remain unknown. Here we employ conditional overexpression of translation initiation factor eIF4E to increase protein synthesis in specific brain cells. We show that exaggerated translation in microglia, but not neurons or astrocytes, leads to autism-like behaviors in male mice. Although microglial eIF4E overexpression elevates translation in both sexes, it only increases microglial density and size in males, accompanied by microglial shift from homeostatic to a functional state with enhanced phagocytic capacity but reduced motility and synapse engulfment. Consequently, cortical neurons in the mice have higher synapse density, neuroligins, and excitation-to-inhibition ratio compared to control mice. We propose that functional perturbation of male microglia is an important cause for sex-biased ASD.
Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines
Authors: Cano-Gamez Eddie , Soskic Blagoje , Roumeliotis Theodoros I. , So Ernest , Smyth Deborah J. , Baldrighi Marta , Willé David , Nakic Nikolina , Esparza-Gordillo Jorge , Larminie Christopher G. C. , Bronson Paola G. , Tough David F. , Rowan Wendy C. , Choudhary Jyoti S. , Trynka Gosia
Published: April 2020

Naïve CD4+T cells coordinate the immune response by acquiring an effector phenotype in response to cytokines. However, the cytokine responses in memory T cells remain largely understudied. Here we use quantitative proteomics, bulk RNA-seq, and single-cell RNA-seq of over 40,000 human naïve and memory CD4+T cells to show that responses to cytokines differ substantially between these cell types. Memory T cells are unable to differentiate into the Th2 phenotype, and acquire a Th17-like phenotype in response to iTreg polarization. Single-cell analyses show that T cells constitute a transcriptional continuum that progresses from naïve to central and effector memory T cells, forming an effectorness gradient accompanied by an increase in the expression of chemokines and cytokines. Finally, we show that T cell activation and cytokine responses are influenced by the effectorness gradient. Our results illustrate the heterogeneity of T cell responses, furthering our understanding of inflammation.
Single-atom-layer traps in a solid electrolyte for lithium batteries
Authors: Zhu Feng , Islam Md Shafiqul , Zhou Lin , Gu Zhenqi , Liu Ting , Wang Xinchao , Luo Jun , Nan Ce-Wen , Mo Yifei , Ma Cheng
Published: April 2020

In order to fully understand the lithium-ion transport mechanism in solid electrolytes for batteries, not only the periodic lattice but also the non-periodic features that disrupt the ideal periodicity must be comprehensively studied. At present only a limited number of non-periodic features such as point defects and grain boundaries are considered in mechanistic studies. Here, we discover an additional type of non-periodic feature that significantly influences ionic transport; this feature is termed a “single-atom-layer trap” (SALT). In a prototype solid electrolyte Li0.33La0.56TiO3, the single-atom-layer defects that form closed loops, i.e., SALTs, are found ubiquitous by atomic-resolution electron microscopy. According to ab initio calculations, these defect loops prevent large volumes of materials from participating in ionic transport, and thus severely degrade the total conductivity. This discovery points out the urgency of thoroughly investigating different types of non-periodic features, and motivates similar studies for other solid electrolytes.
Limiting oxidative DNA damage reduces microbe-induced colitis-associated colorectal cancer
Authors: Irrazabal Thergiory , Thakur Bhupesh K. , Kang Mingsong , Malaise Yann , Streutker Catherine , Wong Erin O. Y. , Copeland Julia , Gryfe Robert , Guttman David S. , Navarre William W. , Martin Alberto
Published: April 2020

Inflammatory bowel disease patients have a greatly increased risk of developing colitis-associated colon cancer (CAC); however, the basis for inflammation-induced genetic damage requisite for neoplasia is unclear. Using three models of CAC, we find that sustained inflammation triggers 8-oxoguanine DNA lesions. Strikingly, antioxidants or iNOS inhibitors reduce 8-oxoguanine and polyps in CAC models. Because the mismatch repair (MMR) system repairs 8-oxoguanine and is frequently defective in colorectal cancer (CRC), we test whether 8-oxoguanine mediates oncogenesis in a Lynch syndrome (MMR-deficient) model. We show that microbiota generates an accumulation of 8-oxoguanine lesions in MMR-deficient colons. Accordingly, we find that 8-oxoguanine is elevated in neoplastic tissue of Lynch syndrome patients compared to matched untransformed tissue or non-Lynch syndrome neoplastic tissue. While antioxidants reduce 8-oxoguanine, they do not reduce CRC in Lynch syndrome models. Hence, microbe-induced oxidative/nitrosative DNA damage play causative roles in inflammatory CRC models, but not in Lynch syndrome models.
Climate change rapidly warms and acidifies Australian estuaries
Authors: Scanes Elliot , Scanes Peter R. , Ross Pauline M.
Published: April 2020

Climate change is impacting ecosystems worldwide. Estuaries are diverse and important aquatic ecosystems; and yet until now we have lacked information on the response of estuaries to climate change. Here we present data from a twelve-year monitoring program, involving 6200 observations of 166 estuaries along >1100 kilometres of the Australian coastline encompassing all estuary morphologies. Estuary temperatures increased by 2.16 °C on average over 12 years, at a rate of 0.2 °C year−1, with waters acidifying at a rate of 0.09 pH units and freshening at 0.086 PSU year−1. The response of estuaries to climate change is dependent on their morphology. Lagoons and rivers are warming and acidifying at the fastest rate because of shallow average depths and limited oceanic exchange. The changes measured are an order of magnitude faster than predicted by global ocean and atmospheric models, indicating that existing global models may not be useful to predict change in estuaries.
Invasive earthworms unlock arctic plant nitrogen limitation
Authors: Blume-Werry Gesche , Krab Eveline J. , Olofsson Johan , Sundqvist Maja K. , Väisänen Maria , Klaminder Jonatan
Published: April 2020

Arctic plant growth is predominantly nitrogen (N) limited. This limitation is generally attributed to slow soil microbial processes due to low temperatures. Here, we show that arctic plant-soil N cycling is also substantially constrained by the lack of larger detritivores (earthworms) able to mineralize and physically translocate litter and soil organic matter. These new functions provided by earthworms increased shrub and grass N concentration in our common garden experiment. Earthworm activity also increased either the height or number of floral shoots, while enhancing fine root production and vegetation greenness in heath and meadow communities to a level that exceeded the inherent differences between these two common arctic plant communities. Moreover, these worming effects on plant N and greening exceeded reported effects of warming, herbivory and nutrient addition, suggesting that human spreading of earthworms may lead to substantial changes in the structure and function of arctic ecosystems.