bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Modeling Study of Nutrient Transport and Dynamics Over the Northern Slope of the South China Sea
Authors: Lu Zhongming , Gan Jianping 
Published: May 2023

AbstractUsing observed data and results from a numerical model, we investigate the coupled physical‐biogeochemical processes that result from water exchanges between the South China Sea (SCS) and the western Pacific Ocean (WPO) and between the shelf and deep basin along the biophysically active continental slope. We study the nutrient transport and dynamics over the northern slope of the SCS where the main branch of the SCS basin circulation facilitates water exchange between the SCS and the WPO. Our results show that the nutrient flux consistently flows year‐round into the slope region from the WPO and that the along‐slope and cross‐slope transports regulate the nutrient budget in the region. The nutrient transport concentrates mainly in the upper 1,000 m and exhibits significant seasonality. We found that cross‐isobath motion is key to fueling nutrients for biological production along the slope and throughout the SCS. When the persistent westward slope current interacts with the variable sloping topography, a unique upslope/downslope nutrient transport occurs along convex/concave isobaths. Vertical turbulent mixing becomes the main nutrient source in the upper mixed layer, and vertical advection becomes the major contributor of nutrients to the subsurface layer. Biological production dominates the nutrient sink in both layers. Horizontal advection is also an important sink in winter when the slope current is the strongest due to the enhanced northeasterly monsoon and the Kuroshio intrusion. Our findings provide an insightful understanding on the critical role of nutrient transport over the slope in the overall ecosystem dynamics of the marginal SCS.
Exceptional Wildfire Enhancements of PAN, C2H4, CH3OH, and HCOOH Over the Canadian High Arctic During August 2017
Authors: Wizenberg T. , Strong K. , Jones D. B. A. , Lutsch E. , Mahieu E. , Franco B. , Clarisse L. 
Published: May 2023

AbstractExtreme enhancements in the total columns of carbon monoxide (CO), peroxyacetyl nitrate (PAN), ethylene (C2H4), methanol (CH3OH), and formic acid (HCOOH) were observed over the Canadian high Arctic during the period of 17–22 August 2017 by a ground‐based Fourier transform infrared (FTIR) spectrometer at Eureka, Nunavut (80.05°N, 86.42°W), and by the Infrared Atmospheric Sounding Interferometer (IASI) satellite instruments. These enhancements have been attributed to wildfires in British Columbia (BC) and the Northwest Territories (NWT) of Canada, and represent the largest short‐term perturbations of PAN, C2H4, and HCOOH above ambient concentrations over the 14‐year (2006–2020) Eureka time‐series. Enhancement ratios, emission ratios, and emission factors relative to CO were calculated for all species for both FTIR and IASI observations. The C2H4 and HCOOH emission factors are significantly larger than previous studies, suggesting unusually high emissions from these fires. The wildfire plumes were also simulated using the GEOS‐Chem model. Initial GEOS‐Chem simulations displayed a severe under‐estimation relative to observations for these fire plumes resulting from the injection height scheme of the model. Sensitivity tests highlighted that injection heights of 12.5 km for BC (based on previous studies) and 10 km for the NWT fires yielded the strongest correlations with ground‐based measurements. Applying these injection heights to the model significantly improves the simulated plume transport and agreement with ground‐ and space‐based observations. GEOS‐Chem was also used to estimate the magnitude of secondary in‐plume production of CH3OH and HCOOH; it was found to be an important component (∼18%) of the enhanced HCOOH columns at Eureka.
Orographic Cirrus and Its Radiative Forcing in NCAR CAM6
Authors: Lyu Kai , Liu Xiaohong , Bacmeister Julio , Zhao Xi , Lin Lin , Shi Yang , Sourdeval Odran 
Published: May 2023

AbstractCirrus clouds play an important role in the Earth's radiative energy budget, thereby affecting the climate state and climate change. Orographic gravity wave (OGW)‐induced sub‐grid scale vertical velocity (i.e., cooling rate) is not resolved by large‐scale models and its impact on ice formation in cirrus clouds is not well quantified. In this study, one sub‐grid scale OGW scheme (e.g., McFarlane) is used in the Community Atmosphere Model version 6 (CAM6) to generate vertical velocity variance (σw) for cirrus formation. Results from the default model and simulations with the OGW‐induced σw are evaluated against the DOE ARM Small Particles in Cirrus (SPARTICUS) campaign observations. The OGW based on the McFarlane scheme increases the sub‐grid scale σw over mountains compared to the default model and improves the model agreement with the SPARTICUS observations. Larger σw due to OGWs can trigger more frequent homogeneous nucleation in orographic cirrus and generates a higher number concentration of ice crystals observed during the SPARTICUS campaign. Moreover, our evaluation of the model simulations against satellite observations indicates that the McFarlane scheme generates high in‐cloud ice number concentrations (>200 L−1) in the upper troposphere over mountains and high plateaus at mid‐ and high‐latitudes of the winter hemisphere as shown in the observations. More ice crystals with smaller sizes absorb more infrared radiation (+0.523 ± 0.125 W m−2). The net radiative cloud forcing change at the top of the atmosphere is +0.330 W m−2 due to the orographic cirrus.
Posterior Assessment of Parameters in a Time Domain Random Walk Model of Partitioning Tracer Tests in Two‐Phase Flow Scenarios
Authors: Janetti Emanuela Bianchi , Guadagnini Alberto , Riva Monica 
Published: May 2023

AbstractWe provide a reliable and efficient methodological framework for the interpretation of laboratory‐scale partitioning tracer test data under uncertainty. The proposed approach rests on a Time domain random walk (TDRW) particle tracking methodology. The range of applicability of the latter is extended to include transport of partitioning tracers upon considering retardation and trapping mechanisms. A classical maximum likelihood (ML) approach is applied considering the extensive set of experimental observations of Dwarakanath et al. (1999, https://doi.org/10.1021/es990082v). This yields best estimates of model parameters, including residual immobile phase saturation, the partition coefficient and the parameters of the memory function employed to simulate the impact of solute trapping. Experimental observations of the partition coefficient are included in the objective function upon relying on a regularization term. We show that considering these types of information, which are typically obtained through batch experiments, is important to attain joint estimates of the partition coefficient and of residual immobile phase saturation. Sample probability distributions of model parameters conditional on available data are then assessed through a stochastic inverse modeling approach. This step poses a signiﬁcant challenge in terms of computational effort and is performed through a reduced order surrogate model. Our results show that the TDRW‐based approach can effectively capture the key features of the observed breakthrough curves of the various partitioning tracers analyzed and provide satisfactory estimates of residual immobile phase saturation.
Tidal Response of Seismic Wave Velocity at Shallow Crust in Japan
Authors: Takano Tomoya , Nishida Kiwamu 
Published: May 2023

AbstractMicrocracks in geomaterials cause variations in the elastic moduli under applied strain, thereby creating seismic wave velocity variations. These are crucial for understanding the dynamic processes of the crust, such as fault‐zone damage, healing, and volcanic activities. Solid earth tides have been used to detect seismic velocity changes responding to crustal‐scale deformations. However, no prior research has explored the characteristics of the seismic velocity variations caused by large‐scale tidal deformation. To systematically evaluate the tidal response to velocity variations, we developed a new method that utilized the flexibility of a state‐space model. The tidal response was derived from hourly stacked noise autocorrelations using a seismic interferometry method throughout Japan. In particular, large tide‐induced seismic velocity changes were observed in the low S‐wave velocity region of the shallow crust. Overall, the tidal responses of velocity variations can provide new insights into the response mechanisms of the shallow crust to applied strain.
Revisiting Raindrop Axis Ratios Based on 3D Oblate Spheroidal Reconstruction: 2D Video Disdrometer Observations During Tropical Cyclone Passages
Authors: Zheng Hepeng , Zhang Yun , Li Haoran , Wu Zuhang , Zhou Zeming 
Published: May 2023

AbstractRaindrops are usually parameterized by oblate spheroids with axis ratios (ARs) determined from projected images. However, the adequacy of representing the 3‐Dimensional (3D) nature of raindrops with their 2‐Dimensional (2D) shadows remains an open question. This study reexamines raindrop AR parameterizations by applying a 3D oblate spheroidal reconstruction algorithm to 2D video disdrometer (2DVD) observations during the passages of 14 tropical cyclones. The results reveal an appreciable AR overestimation for large raindrops when retrieved from a single camera and especially for 2DVD raw products. This overestimation propagates into the simulated differential reflectivity (ZDR), resulting in an underestimation of ZDR by up to 0.5 dB at X‐band when large raindrops dominate the raindrop size distribution (RSD), which would introduce an underestimation of more than 20% for heavy rain rate (>60 mm hr−1) estimation by polarimetric radar. In precipitating systems with drastically changing RSDs, the importance of adopting more realistic ARs is warranted.
Different Magmatic‐Hydrothermal Fluids at the Same Magma Source Support Distinct Microbial Communities: Evidence From In Situ Detection
Authors: Xi Shichuan , Sun Qinglei , Huang Ruifang , Luan Zhendong , Du Zengfeng , Li Lianfu , Zhang Xin 
Published: May 2023

AbstractSubmarine magmatic‐hydrothermal systems are dominated by volcanism and generate unique biocenoses. However, the relationships between the microbial communities and the broad range of chemical and physical variability within the systems are poorly understood. Here, a high‐precision in situ Raman quantitative technique was used for the hydrothermal fluids at the Onsen site and a newly found site named Faxian in a magmatic‐hydrothermal system at the DESMOS caldera, Manus back‐arc basin. The maximum in situ H2 concentration (8.56 mmol/kg) at the Onsen site is the highest value ever reported in similar hydrothermal systems. In contrast, the diffuse fluid at the Faxian site was characterized by rich H2S (7.78 mmol/kg) but without H2. The differences in mixing contents of seawater induced different geochemical reactions and fluxes of hydrogen and hydrogen sulfide. Furthermore, the existence of hydrogen‐ and sulfide‐oxidizing genes suggests that the oxidation of hydrogen and hydrogen sulfide are the energy sources of the microbial communities at the two sites even within the same magma source. The in situ quantitative analyses of different types of fluids provide implications on the materials fluxes in the magmatic‐hydrothermal system, and the relationships between widespread submarine volcanic activities and life in early Earth.
m6A methylation regulates hypoxia-induced pancreatic cancer glycolytic metabolism through ALKBH5-HDAC4-HIF1α positive feedback loop
Authors: Liu Xiaoyan , Feng Maoxiao , Hao Xiaodong , Gao Zihan , Wu Zhaoxin , Wang Yuli , Du Lutao , Wang Chuanxin 
Published: May 2023

AbstractPancreatic cancer (PC) is the most hypoxic cancer type among solid tumors. The dynamic changes of RNA N6-methyl-adenosine (m6A) contribute to tumor cells adaption to hypoxic microenvironmental. However, the regulatory mechanisms of hypoxia response in PC remains elusive. Here, we reported that the m6A demethylase ALKBH5 mediated a decrease of total mRNA m6A modification during hypoxia. Subsequently, methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA sequencing (RNA-seq) revealed transcriptome-wide gene expression alteration and identified histone deacetylase type 4 (HDAC4) as a key target gene of m6A modification under hypoxic conditionds. Mechanistically, m6A methylation recognized by m6A reader-YTHDF2 enhanced the stability of HDAC4, and then promoted glycolytic metabolism and migration of PC cells. Our assays also demonstrated that hypoxia-induced HDAC4 enhanced HIF1a protein stability, and overexpressed HIF1a promoted transcription of ALKBH5 in hypoxic pancreatic cancer cells. Together, these results found a ALKBH5/HDAC4/HIF1α positive feedback loop for cellular response to hypoxia in pancreatic cancer. Our studies uncover the crosstalk between histone acetylation and RNA methylation modification on layer of epigenetic regulation.
miR-137–LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma
Authors: Yan Ruyu , Liu Dan , Wang Junjie , Liu Minxia , Guo Hongjuan , Bai Jing , Yang Shuo , Chang Jun , Yao Zhihong , Yang Zuozhang , Blom Tomas , Zhou Kecheng 
Published: May 2023

AbstractOsteosarcoma (OS) is a rare malignant bone tumor but is one leading cause of cancer mortality in childhood and adolescence. Cancer metastasis accounts for the primary reason for treatment failure in OS patients. The dynamic organization of the cytoskeleton is fundamental for cell motility, migration, and cancer metastasis. Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is an oncogene participating in various biological progress central to cancer biogenesis. However, the potential roles of LAPTM4B in OS and the related mechanisms remain unknown. Here, we established the elevated LAPTM4B expression in OS, and it is essential in regulating stress fiber organization through RhoA–LIMK–cofilin signaling pathway. In terms of mechanism, our data revealed that LAPTM4B promotes RhoA protein stability by suppressing the ubiquitin-mediated proteasome degradation pathway. Moreover, our data show that miR-137, rather than gene copy number and methylation status, contributes to the upregulation of LAPTM4B in OS. We report that miR-137 is capable of regulating stress fiber arrangement, OS cell migration, and metastasis via targeting LAPTM4B. Combining results from cells, patients’ tissue samples, the animal model, and cancer databases, this study further suggests that the miR-137–LAPTM4B axis represents a clinically relevant pathway in OS progression and a viable target for novel therapeutics.
Methadone alters transcriptional programs associated with synapse formation in human cortical organoids
Authors: Dwivedi Ila , Caldwell Andrew B. , Zhou Dan , Wu Wei , Subramaniam Shankar , Haddad Gabriel G. 
Published: May 2023

AbstractOpioid use disorder (OUD) among pregnant women has become an epidemic in the United States. Pharmacological interventions for maternal OUD most commonly involve methadone, a synthetic opioid analgesic that attenuates withdrawal symptoms and behaviors linked with drug addiction. However, evidence of methadone’s ability to readily accumulate in neural tissue, and cause long-term neurocognitive sequelae, has led to concerns regarding its effect on prenatal brain development. We utilized human cortical organoid (hCO) technology to probe how this drug impacts the earliest mechanisms of cortico-genesis. Bulk mRNA sequencing of 2-month-old hCOs chronically treated with a clinically relevant dose of 1 μM methadone for 50 days revealed a robust transcriptional response to methadone associated with functional components of the synapse, the underlying extracellular matrix (ECM), and cilia. Co-expression network and predictive protein-protein interaction analyses demonstrated that these changes occurred in concert, centered around a regulatory axis of growth factors, developmental signaling pathways, and matricellular proteins (MCPs). TGFβ1 was identified as an upstream regulator of this network and appeared as part of a highly interconnected cluster of MCPs, of which thrombospondin 1 (TSP1) was most prominently downregulated and exhibited dose-dependent reductions in protein levels. These results demonstrate that methadone exposure during early cortical development alters transcriptional programs associated with synaptogenesis, and that these changes arise by functionally modulating extra-synaptic molecular mechanisms in the ECM and cilia. Our findings provide novel insight into the molecular underpinnings of methadone’s putative effect on cognitive and behavioral development and a basis for improving interventions for maternal opioid addiction.
NAPE-PLD deletion in stress-TRAPed neurons results in an anxiogenic phenotype
Authors: Tevosian Margaryta , Todorov Hristo , Lomazzo Ermelinda , Bindila Laura , Ueda Natsuo , Bassetti Davide , Warm Davide , Kirischuk Sergei , Luhmann Heiko J. , Gerber Susanne , Lutz Beat 
Published: May 2023

AbstractAnandamide (AEA) is an endogenous ligand of the cannabinoid CB1 and CB2 receptors, being a component of the endocannabinoid signaling system, which supports the maintenance or regaining of neural homeostasis upon internal and external challenges. AEA is thought to play a protective role against the development of pathological states after prolonged stress exposure, including depression and generalized anxiety disorder. Here, we used the chronic social defeat (CSD) stress as an ethologically valid model of chronic stress in male mice. We characterized a genetically modified mouse line where AEA signaling was reduced by deletion of the gene encoding the AEA synthesizing enzyme N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD) specifically in neurons activated at the time of CSD stress. One week after the stress, the phenotype was assessed in behavioral tests and by molecular analyses. We found that NAPE-PLD deficiency in neurons activated during the last three days of CSD stress led to an increased anxiety-like behavior. Investigating the molecular mechanisms underlying this phenotype may suggest three main altered pathways to be affected: (i) desensitization of the negative feedback loop of the hypothalamic-pituitary-adrenal axis, (ii) disinhibition of the amygdala by the prefrontal cortex, and (iii) altered neuroplasticity in the hippocampus and prefrontal cortex.
Effects of the mGlu2/3 receptor agonist LY379268 on two models of disturbed auditory evoked brain oscillations in mice
Authors: Dormann Oana-Daniela , Schuelert Niklas , Rosenbrock Holger 
Published: May 2023

AbstractCognitive impairment is a core feature of schizophrenia and is poorly addressed by currently available medication. This is partly because the underlying circuits are insufficiently understood, and available animal models for brain dysfunction do not adequately mimic human pathology. To improve the translatability of animal studies and complement behavioral data, EEG measurements are being increasingly used in preclinical research. Brain oscillations are similar across species and can be impaired via several means. In this study, we used two approaches to impair early sensory processing and cortical oscillations in mice: a pharmacological model targeting NMDA receptor function in the whole brain via systemic MK-801 application and an optogenetic model targeting parvalbumin-positive (PV+) interneurons locally in the medial prefrontal cortex (mPFC). We evoked brain activity using auditory stimulation, a tool with high translatability from mouse to human. We then investigated the effect of LY379268, an agonist of mGlu2/3 receptors, a potential therapeutic target for schizophrenia, on single neuron and EEG responses. LY379268 was able to rescue MK-801-induced deficits for a variety of clinically relevant early sensory EEG biomarkers. Single neuron recordings revealed a strong effect of LY379268 on the signal-to-noise ratio during auditory stimulation and optogenetic inhibition of PV+ interneurons. Our results contribute to a better understanding of how group II metabotropic glutamate receptors modulate neuronal population and network activity under sensory stimulation while challenged pharmacologically or optogenetically.
Overexpression of EphB6 and EphrinB2 controls soma spacing of cortical neurons in a mutual inhibitory way
Authors: He Chun-Hui , Song Ning-Ning , Xie Pin-Xi , Wang Yu-Bing , Chen Jia-Yin , Huang Ying , Hu Ling , Li Zhao , Su Jun-Hui , Zhang Xiao-Qing , Zhang Lei , Ding Yu-Qiang 
Published: May 2023

AbstractTo establish functional circuitry, neurons settle down in a particular spatial domain by spacing their cell bodies, which requires proper positioning of the soma and establishing of a zone with unique connections. Deficits in this process are implicated in neurodevelopmental diseases. In this study, we examined the function of EphB6 in the development of cerebral cortex. Overexpression of EphB6 via in utero electroporation results in clumping of cortical neurons, while reducing its expression has no effect. In addition, overexpression of EphrinB2, a ligand of EphB6, also induces soma clumping in the cortex. Unexpectedly, the soma clumping phenotypes disappear when both of them are overexpressed in cortical neurons. The mutual inhibitory effect of EphB6/ EphrinB2 on preventing soma clumping is likely to be achieved via interaction of their specific domains. Thus, our results reveal a combinational role of EphrinB2/EphB6 overexpression in controlling soma spacing in cortical development.
Silencing Notch4 promotes tumorigenesis and inhibits metastasis of triple-negative breast cancer via Nanog and Cdc42
Authors: Tian Yuan , Zhang Peipei , Mou Yajun , Yang Wenxiu , Zhang Junhong , Li Qing , Dou Xiaowei 
Published: May 2023

AbstractElucidation of individual Notch protein biology in specific cancer is crucial to develop safe, effective, and tumor-selective Notch-targeting therapeutic reagents for clinical use [1]. Here, we explored the Notch4 function in triple-negative breast cancer (TNBC). We found that silencing Notch4 enhanced tumorigenic ability in TNBC cells via upregulating Nanog expression, a pluripotency factor of embryonic stem cells. Intriguingly, silencing Notch4 in TNBC cells suppressed metastasis via downregulating Cdc42 expression, a key molecular for cell polarity formation. Notably, downregulation of Cdc42 expression affected Vimentin distribution, but not Vimentin expression to inhibit EMT shift. Collectively, our results show that silencing Notch4 enhances tumorigenesis and inhibits metastasis in TNBC, indicating that targeting Notch4 may not be a potential strategy for drug discovery in TNBC.
Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment
Authors: Ma Weili , Oliveira-Nunes Maria Cecília , Xu Ke , Kossenkov Andrew , Reiner Benjamin C. , Crist Richard C. , Hayden James , Chen Qing 
Published: May 2023

AbstractCancer metastasis to the brain is a significant clinical problem. Metastasis is the consequence of favorable interactions between invaded cancer cells and the microenvironment. Here, we demonstrate that cancer-activated astrocytes create a sustained low-level activated type I interferon (IFN) microenvironment in brain metastatic lesions. We further confirm that the IFN response in astrocytes facilitates brain metastasis. Mechanistically, IFN signaling in astrocytes activates C-C Motif Chemokine Ligand 2 (CCL2) production, which further increases the recruitment of monocytic myeloid cells. The correlation between CCL2 and monocytic myeloid cells is confirmed in clinical brain metastasis samples. Lastly, genetically or pharmacologically inhibiting C-C Motif Chemokine Receptor 2 (CCR2) reduces brain metastases. Our study clarifies a pro-metastatic effect of type I IFN in the brain even though IFN response has been considered to have anti-tumor effects. Moreover, this work expands our understandings on the interactions between cancer-activated astrocytes and immune cells in brain metastasis.