bluuebunny/crossref_metadata_2025_split huggingface dataset:
Logjams and Channel Morphology Influence Sediment Storage, Transformation of Organic Matter, and Carbon Storage Within Mountain Stream Corridors
Authors: Sutfin Nicholas A. , Wohl Ellen , Fegel Timothy , Day Natalie , Lynch Laurel 
Published: May 2021

AbstractThe flow of organic matter (OM) along rivers and retention within floodplains contributes significantly to terrestrial carbon storage and ecosystem function. The storage and cycling of OM largely depend upon hydrogeomorphic characteristics of streams and valleys, including channel geometry and the connectivity of water across and within the floodplain. To examine the role of river morphology on carbon dynamics in mountain streams, we (a) quantify organic carbon (OC) storage in fine sediment, litter, and wood along 24 forested gravel‐bed stream reaches in the Rocky Mountains of CO, USA, (b) examine morphological factors that regulate sediment and OC storage (e.g., channel width, slope, logjams), and (c) utilize fluorescence spectroscopy to examine how the composition of fluorescent dissolved OM in surface water and floodplain fine sediment are influenced by channel morphology. Multivariate regression of the study reaches, which have varying degrees of confinement, slope, and elevation, indicates that OC storage per area is higher in less confined valleys, in lower gradient stream reaches, and at higher elevations. Within unconfined valleys, limited storage of fine sediment and greater microbial transformation of OM in multithread channel reaches decreases OC storage per area (252 ± 39 Mg C ha−1) relative to single‐thread channel reaches (346 ± 177 Mg C ha−1). Positive feedbacks between channel morphology and persistent channel‐spanning logjams that divert flow into multiple channels may limit the aggradation of floodplain fine sediment. Although multithread stream reaches are less effective OC reservoirs, they are hotspots for OM decomposition and provide critical resources to downstream food webs.
Simulated Southern Ocean Upwelling at the Last Glacial Maximum and Early Deglaciation: The Role of Eddy‐Induced Overturning Circulation
Authors: Chen Changlin , Wang Guihua 
Published: May 2021

AbstractWe explore the changes in Southern Ocean upwelling patterns during the last glacial maximum (LGM) and early deglaciation using a fully coupled climate model with ocean eddies parameterized via the Gent‐McWilliams scheme. Relative to the preindustrial climate, the model simulates an equatorward shift of the upwelling of the residual circulation in the Southern Ocean during the LGM, which is consistent with paleo‐evidence of export production. This change in upwelling primarily arose from an altered eddy‐induced meridional overturning circulation (MOC) that resulted from the expanded sea ice and enhanced buoyancy loss around Antarctica during the LGM, which modulated the slope of buoyancy surface in the Southern Ocean. We have also found that there was a poleward shift of the upwelling of the residual circulation in the Southern Ocean during the early deglaciation, which was different than the change in the wind‐driven upwelling and primarily driven by variations in the eddy‐induced MOC.
Rapid Injections of MeV Electrons and Extremely Fast Step‐Like Outer Radiation Belt Enhancements
Authors: Kim H.‐J. , Lee D.‐Y. , Wolf R. , Bortnik J. , Kim K.‐C. , Lyons L. , Choe W. , Noh S.‐J. , Choi K.‐E. , Yue C. , Li J. 
Published: May 2021

AbstractRapid injection of MeV electrons associated with strong substorm dipolarization has been suggested as a potential explanation for some radiation belt enhancement events. However, it has been difficult to quantify the contribution of MeV electron injections to radiation belt enhancements. This paper presents two isolated MeV electron injection events for which we quite precisely quantify how the entire outer‐belt immediately changed with the injections. Tracking detailed outer‐belt evolution observed by Van Allen Probes, for both events, we identify large step‐like relativistic electron enhancements (roughly 1 order of magnitude increase for ∼2 MeV electron fluxes) for L ≳ 3.8 and L ≳ 4.6, respectively, that occurred on ∼30‐min time scales nearly instantaneously with the injections. The enhancements occurred almost simultaneously for 10s keV to multi‐MeV electrons, with the lowest L of enhancement region located farther out for higher energy. The outer‐belt stayed at these new levels for ≳several hours without substantial subsequent enhancements.
On the Relevance of Geodetic Deformation Rates to Earthquake Potential
Authors: Wang Kelin , Zhu Yijie , Nissen Edwin , Shen Zheng‐Kang 
Published: May 2021

AbstractDespite the importance of viscoelasticity in the evolution of crustal stress/strain being widely recognized, the interpretation of interseismic geodetic measurements for assessing earthquake potential is still based overwhelmingly on elastic models. The reasons for this disparity include conflating deformation rates with deformation itself and the lack of a succinct representation of the seismic readiness of a locked fault in a viscoelastic Earth. Using a classical viscoelastic model for strike‐slip faults, we reiterate the commonly overlooked message that, if the recurrence interval is long, most of the strain energy for the next earthquake accrues early in the cycle, and low strain rates later in the cycle by no means indicate diminished rupture potential. Fault stress stays near failure for much of the late interseismic period which may explain why slow slip‐rate faults have more variable recurrence intervals than fast slip‐rate faults. We propose to use displacement deficit instead of slip deficit to represent seismic readiness.
Comprehensive Insights Into O3 Changes During the COVID‐19 From O3 Formation Regime and Atmospheric Oxidation Capacity
Authors: Zhu Shengqiang , Poetzscher James , Shen Juanyong , Wang Siyu , Wang Peng , Zhang Hongliang 
Published: May 2021

AbstractEconomic activities and the associated emissions have significantly declined during the 2019 novel coronavirus (COVID‐19) pandemic, which has created a natural experiment to assess the impact of the emitted precursor control policy on ozone (O3) pollution. In this study, we utilized comprehensive satellite, ground‐level observations, and source‐oriented chemical transport modeling to investigate the O3 variations during the COVID‐19 pandemic in China. Here, we found that the significant elevated O3 in the North China Plain (40%) and Yangtze River Delta (35%) were mainly attributed to the enhanced atmospheric oxidation capacity (AOC) in these regions, associated with the meteorology and emission reduction during lockdown. Besides, O3 formation regimes shifted from VOC‐limited regimes to NOx‐limited and transition regimes with the decline of NOx during lockdown. We suggest that future O3 control policies should comprehensively consider the effects of AOC on the O3 elevation and coordinated regulations of the O3 precursor emissions.
Postwildfire Soil‐Hydraulic Recovery and the Persistence of Debris Flow Hazards
Authors: Thomas Matthew A. , Rengers Francis K. , Kean Jason W. , McGuire Luke A. , Staley Dennis M. , Barnhart Katherine R. , Ebel Brian A. 
Published: May 2021

AbstractDeadly and destructive debris flows often follow wildfire, but understanding of changes in the hazard potential with time since fire is poor. We develop a simulation‐based framework to quantify changes in the hydrologic triggering conditions for debris flows as postwildfire infiltration properties evolve through time. Our approach produces time‐varying rainfall intensity‐duration thresholds for runoff‐ and infiltration‐generated debris flows with physics‐based hydrologic simulations that are parameterized with widely available hydroclimatic, vegetation reflectance, and soil texture data. When we apply our thresholding protocol to a test case in the San Gabriel Mountains (California, USA), the results are consistent with existing regional empirical thresholds and rainstorms that caused runoff‐ and infiltration‐generated debris flows soon after and three years following a wildfire, respectively. We find that the hydrologic triggering mechanisms for the two observed debris flow types are coupled with the effects of fire on the soil saturated hydraulic conductivity. Specifically, the rainfall intensity needed to generate debris flows via runoff increases with time following wildfire while the rainfall duration needed to produce debris flows via subsurface pore‐water pressures decreases. We also find that variations in soil moisture, rainfall climatology, median grain size, and root reinforcement could impact the median annual probability of postwildfire debris flows. We conclude that a simulation‐based method for calculating rainfall thresholds is a tractable approach to improve situational awareness of debris flow hazard in the years following wildfire. Further development of our framework will be important to quantify postwildfire hazard levels in variable climates, vegetation types, and fire regimes.
Targeting of adipose tissue macrophages by bee venom phospholipase A2 attenuates high-fat diet-induced obesity
Authors: Jeong Hyunju , Lee Chanju , Cheng Chenyu , Chou Hung Chun , Yang HyeJin , Bae Hyunsu 
Published: May 2021

Abstract
Background/objectives
Adipose tissue macrophages (ATMs) exist in either the M1 or M2 form. The anti-inflammatory M2 ATMs accumulate in lean individuals, whereas the pro-inflammatory M1 ATMs accumulate in obese individuals. Bee venom phospholipase A2 (bvPLA2), a major component in honeybee (Apis mellifera) venom, exerts potent anti-inflammatory effects via interactions with regulatory T cells (Treg) and macrophages. This study investigated the effects of bvPLA2 on a high-fat diet (HFD)-induced obesity in mice.

Subjects/methods
For in vivo experiments, male C57BL/6, CD206-deficient, and Treg-depleted mice models were fed either a normal diet 41.86 kJ (ND, 10 kcal% fat) or high-fat diet 251.16 kJ (HFD, 60 kcal% fat). Each group was i.p. injected with PBS or bvPLA2 (0.5 mg/kg) every 3 days for 11 weeks. Body weight and food intake were measured weekly. Histological changes in the white adipose tissue (WAT), liver, and kidney as well as the immune phenotypes of the WAT were examined. Immune cells, cytokines, and lipid profiles were also evaluated. The direct effects of bvPLA2 on 3T3-L1 pre-adipocytes and bone marrow-derived macrophages were measured in vitro.

Results
bvPLA2 markedly decreased bodyweight in HFD-fed mice. bvPLA2 treatment also decreased lipid accumulation in the liver and reduced kidney inflammation in the mice. It was confirmed that bvPLA2 exerted immunomodulatory effects through the CD206 receptor. In addition, bvPLA2 decreased M1 ATM and alleviated the M1/M2 imbalance in vivo. However, bvPLA2 did not directly inhibit adipogenesis in the 3T3-L1 adipose cells in vitro.

Conclusions
bvPLA2 is a potential therapeutic strategy for the management of obesity by regulating adipose tissue macrophage homeostasis.
WAPL induces cervical intraepithelial neoplasia modulated with estrogen signaling without HPV E6/E7
Authors: Kumagai Katsuyoshi , Takanashi Masakatsu , Ohno Shin-ichiro , Harada Yuichirou , Fujita Koji , Oikawa Keiki , Sudo Katsuko , Ikeda Shun-ichi , Nishi Hirotaka , Oikawa Kosuke , Kuroda Masahiko 
Published: May 2021

AbstractSince cervical cancer still afflicts women around the world, it is necessary to understand the underlying mechanism of cervical cancer development. Infection with HPV is essential for the development of cervical intraepithelial neoplasia (CIN). In addition, estrogen receptor signaling is implicated in the development of cervical cancer. Previously, we have isolated human wings apart-like (WAPL), which is expected to cause chromosomal instability in the process of HPV-infected precancerous lesions to cervical cancer. However, the role of WAPL in the development of CIN is still unknown. In this study, in order to elucidate the role of WAPL in the early lesion, we established WAPL overexpressing mice (WAPL Tg mice) and HPV E6/E7 knock-in (KI) mice. WAPL Tg mice developed CIN lesion without HPV E6/E7. Interestingly, in WAPL Tg mice estrogen receptor 1 (ESR1) showed reduction as compared with the wild type, but cell growth factors MYC and Cyclin D1 controlled by ESR1 expressed at high levels. These results suggested that WAPL facilitates sensitivity of ESR1 mediated by some kind of molecule, and as a result, affects the expression of MYC and Cyclin D1 in cervical cancer cells. To detect such molecules, we performed microarray analysis of the uterine cervix in WAPL Tg mice, and focused MACROD1, a co-activator of ESR1. MACROD1 expression was increased in WAPL Tg mice compared with the wild type. In addition, knockdown of WAPL induced the downregulation of MACROD1, MYC, and Cyclin D1 but not ESR1 expression. Furthermore, ESR1 sensitivity assay showed lower activity in WAPL or MACROD1 downregulated cells than control cells. These data suggested that WAPL increases ESR1 sensitivity by activating MACROD1, and induces the expression of MYC and Cyclin D1. Therefore, we concluded that WAPL not only induces chromosomal instability in cervical cancer tumorigenesis, but also plays a key role in activating estrogen receptor signaling in early tumorigenesis.
N6-methyladenosine demethylase FTO impairs hepatic ischemia–reperfusion injury via inhibiting Drp1-mediated mitochondrial fragmentation
Authors: Du Ying Dong , Guo Wen Yuan , Han Cong Hui , Wang Ying , Chen Xiao Song , Li Da Wei , Liu Jin Long , Zhang Ming , Zhu Nan , Wang Xin 
Published: May 2021

AbstractDespite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia–reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro. Moreover, dynamin-related protein 1 (Drp1) was a downstream target of FTO in the progression of HIRI. FTO contributed to the hepatic protective effect via demethylating the mRNA of Drp1 and impairing the Drp1-mediated mitochondrial fragmentation. Collectively, our findings demonstrated the functional importance of FTO-dependent hepatic m6A methylation during HIRI and provided valuable insights into the therapeutic mechanisms of FTO.
Circular RNA hsa_circ_0006401 promotes proliferation and metastasis in colorectal carcinoma
Authors: Zhang Chenjing , Zhou Xiaolu , Geng Xiaoge , Zhang Yu , Wang Jingya , Wang Yanan , Jing Jiyong , Zhou Xuelong , Pan Wensheng 
Published: May 2021

AbstractDysregulation of circular RNA (circRNA) expression is involved in the progression of cancer. Here, we aimed to study the potential function of hsa_circ_0006401 in colorectal cancer (CRC). CircRNA hsa_circ_0006401 expression levels in CRC and adjacent nontumor tissues were analyzed by real-time quantitative PCR (qRT-PCR) and circRNA in situ hybridization (RNA-ISH). Then, CRC cell proliferation was assessed by cell counting. Wound-healing and transwell assays were utilized to detect the effect of hsa_circ_0006401 on CRC migration. A circRNA-ORF construct was created, and a specific antibody against the splice junction of hsa_circ_0006401 was prepared. Finally, the proteins directly binding to hsa_circ_0006401 peptides were identified by immunoprecipitation combined with mass spectrometry. In our study, we found hsa_circ_0006401 was closely related to CRC metastasis and exhibited upregulated expression in metastatic CRC tissue samples. Proliferation and migration were inhibited in vitro when hsa_circ_0006401 expression was silenced. Downregulation of hsa_circ_0006401 expression decreased CRC proliferation and liver metastasis in vivo. A 198-aa peptide was encoded by sequences of the splice junction absent from col6a3. Hsa_circ_0006401 promoted CRC proliferation and migration by encoding the hsa_circ_0006401 peptide. Hsa_circ_0006401 peptides decreased the mRNA and protein level of the host gene col6a3 by promoting col6a3 mRNA stabilation. In conclusion, our study revealed that circRNAs generated from col6a3 that contain an open-reading frame (ORF) encode a novel 198-aa functional peptide and hsa_circ_0006401 peptides promote stability of the host gene col6a3 mRNA to promote CRC proliferation and metastasis.
Interrogation of gender disparity uncovers androgen receptor as the transcriptional activator for oncogenic miR-125b in gastric cancer
Authors: Liu Ben , Zhou Meng , Li Xiangchun , Zhang Xining , Wang Qinghua , Liu Luyang , Yang Meng , Yang Da , Guo Yan , Zhang Qiang , Zheng Hong , Wang Qiong , Li Lian , Chu Xinlei , Wang Wei , Li Haixin , Song Fengju , Pan Yuan , Zhang Wei , Chen Kexin 
Published: May 2021

AbstractThere is a male preponderance in gastric cancer (GC), which suggests a role of androgen and androgen receptor (AR). However, the mechanism of AR signaling in GC especially in female patients remains obscure. We sought to identify the AR signaling pathway that might be related to prognosis and examine the potential clinical utility of the AR antagonist for treatment. Deep learning and gene set enrichment analysis was used to identify potential critical factors associated with gender bias in GC (n = 1390). Gene expression profile analysis was performed to screen differentially expressed genes associated with AR expression in the Tianjin discovery set (n = 90) and TCGA validation set (n = 341). Predictors of survival were identified via lasso regression analyses and validated in the expanded Tianjin cohort (n = 373). In vitro and in vivo experiments were established to determine the drug effect. The GC gender bias was attributable to sex chromosome abnormalities and AR signaling dysregulation. The candidates for AR-related gene sets were screened, and AR combined with miR-125b was associated with poor prognosis, particularly among female patients. AR was confirmed to directly regulatemiR-125bexpression. AR-miR-125b signaling pathway inhibited apoptosis and promoted proliferation. AR antagonist, bicalutamide, exerted anti-tumor activities and induced apoptosis both in vitro and in vivo, using GC cell lines and female patient-derived xenograft (PDX) model. We have shed light on gender differences by revealing a hormone-regulated oncogenic signaling pathway in GC. Our preclinical studies suggest that AR is a potential therapeutic target for this deadly cancer type, especially in female patients.
GIPC2 is an endocrine-specific tumor suppressor gene for both sporadic and hereditary tumors of RET- and SDHB-, but not VHL-associated clusters of pheochromocytoma/paraganglioma
Authors: Dong Yeqing , Huang Yongsheng , Fan Chengyan , Wang Liang , Zhang Ran , Li Wenhua , Guo Zhengguang , Wang Dong , Zheng Zhi 
Published: May 2021

AbstractPheochromocytoma/paraganglioma (PPGL) is an endocrine tumor of the chromaffin cells in the adrenal medulla or the paraganglia. Currently, about 70% of PPGLs can be explained by germline or somatic mutations in several broadly expressed susceptibility genes including RET, VHL, and SDHB, while for the remaining, mainly sporadic cases, the pathogenesis is still unclear. Even for known susceptible genes, how mutations in these mostly ubiquitous genes result in tissue-specific pathogenesis remains unanswered, and why RET-mutated tumors almost always occur in the adrenal while SDHB-mutated tumors mostly occur extra-adrenal remains a mystery. By analyzing 22 sporadic PPGLs using SNP 6.0 genotyping arrays combined with expression profiling of 4 normal and 4 tumor tissues, we identified GIPC2, a gene located at 1p31.1 with preferential expression in adrenal and inducible by adrenal glucocorticoid, as a novel putative tumor suppressor gene for PPGLs. Copy number deletion and GIPC2 promoter hypermethylation but not GIPC2 mutation, accompanied with reduced GIPC2 expression, were observed in 39 of 55 PPGLs in our cohort. Examination of a published expression database consisting of 188 PPGLs found little GIPC2 expression in Cluster 1A (SDHx-associated) and Cluster 2A (NF1/RET-associated) tumors, but less pronounced reduction of GIPC2 expression in Cluster 1B (VHL-associated) and Cluster 2B/2C tumors. GIPC2 induced p27, suppressed MAPK/ERK and HIF-1ɑ pathways as well as cancer cell proliferation. Overexpressing GIPC2 in PC12 cells inhibited tumor growth in nude mice. We found GIPC2 interacted with the nucleoprotein NONO and both proteins regulated p27 transcription through the same GGCC box on p27 promoter. Significantly, low expression of both GIPC2 and p27 was associated with shorter disease-free survival time of PPGLs patients in the TCGA database. We found that PPGL-causing mutations in RET and in SDHB could lead to primary rat adrenal chromaffin cell proliferation, ERK activation, and p27 downregulation, all requiring downregulating GIPC2. Notably, the RET-mutant effect required the presence of dexamethasone while the SDHB-mutant effect required its absence, providing a plausible explanation for the tumor location preference. In contrast, the PPGL-predisposing VHL mutations had no effect on proliferation and GIPC2 expression but caused p53 downregulation and reduced apoptosis in chromaffin cells compared with wild-type VHL. Thus, our study raises the importance of cortical hormone in PPGL development, and GIPC2 as a novel tumor suppressor provides a unified molecular mechanism for the tumorigenesis of both sporadic and hereditary tumors of Clusters 1A and 2A concerning SDHB and RET, but not tumors of Cluster 1B concerning VHL and other clusters.
Attenuation of inhibitory PAS domain protein-induced cell death by synthetic peptides derived from Mcl-1 transmenbrane domain
Authors: Kasai Shuya , Yasumoto Ken-ichi , Sogawa Kazuhiro 
Published: May 2021

AbstractExpression of Inhibitory PAS domain protein (IPAS) induces apoptosis by inhibiting the anti-apoptotic activity of mitochondrial pro-survival proteins including Bcl-xL and Mcl-1 through direct binding. Analysis to examine the IPAS-binding region in Bcl-xL demonstrated that the C-terminal transmembrane (TM) domain is indispensable for the specific binding. A chimeric protein composed of the TM domain of Mcl-1 fused to the C-terminus of Citrine also exhibited a binding affinity to IPAS, and markedly attenuated apoptosis caused by the overexpression of Cerulean-IPAS in SH-SY5Y cells. HIV-1 TAT cell-penetrating peptide-conjugated synthetic peptides that cover whole or parts of the Mcl-1 TM domain showed anti-apoptotic activity in the CoCl2-induced cell death in PC12 cells. Administration of these highly effective anti-apoptotic peptides to mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that produces a reliable mouse model of Parkinson’s disease (PD) decreased neuronal cell loss in the substantia nigra pars compacta. Therefore, the peptides may be considered promising therapeutic agents for neurodegenerative disorders such as PD and stroke.