bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coarsening Dynamics of 2D Subaqueous Dunes
Authors: Jarvis P. A. , Bacik K. A. , Narteau C. , Vriend N. M. 
Published: February 2022

AbstractFluid flow over an initially flat granular bed leads to the formation of a surface‐wave instability. The sediment bed profile coarsens and increases in amplitude and wavelength as disturbances develop from ripples into dunes. We perform experiments and numerical simulations to quantify both the temporal evolution of bed properties and the relationship between the initial growth rate and the friction velocity u∗. Experimentally, we study underwater bedforms originating from a thin horizontal particle layer in a narrow and counter‐rotating annular flume. We investigate the role of flow speed, flow depth and initial bed thickness on dune evolution. Bedforms evolve from small, irregular disturbances on the bed surface to rapidly growing connected terraces (2D equivalent of transverse dunes) before splitting into discrete dunes. Throughout much of this process, growth is controlled by dune collisions which are observed to result in either coalescence or ejection (mass exchange). We quantify the coarsening process by tracking the temporal evolution of the bed amplitude and wavelength. Additionally, we perform Large Eddy Simulations (LES) of the fluid flow inside the flume to relate the experimental conditions to u∗. By combining the experimental observations with the LES results, we find that the initial dune growth rate scales approximately as . These results can motivate models of finite‐amplitude dune growth from thin sediment layers that are important in both natural and industrial settings.
Eutrophication and Deoxygenation Forcing of Marginal Marine Organic Carbon Burial During the PETM
Authors: Papadomanolaki Nina M. , Sluijs Appy , Slomp Caroline P. 
Published: February 2022

AbstractThe Paleocene‐Eocene Thermal Maximum (PETM) is recognized globally by a negative excursion in stable carbon isotope ratios (δ13C) in sedimentary records, termed the carbon isotope excursion (CIE). Based on the CIE, the cause, duration, and mechanisms of recovery of the event have been assessed. Here, we focus on the role of increased organic carbon burial on continental margins as a key driver of CO2drawdown and global exogenic δ13C during the recovery phase. Using new and previously published sediment proxy data, we show evidence for widespread enhanced primary production, low oxygen waters, and high organic carbon (Corg) burial in marginal and restricted environments throughout the δ13C excursion. With a new biogeochemical box model for deep and marginal environments, we show that increased phosphorus availability and water column stratification on continental margins can explain the increased Corgburial during the PETM. Deoxygenation and recycling of phosphorus relative to Corgwere relatively mild, compared to modern day anoxic marine systems. Our model reproduces the conditions reconstructed by field data, resulting in a burial of 6,000 Pg across the PETM, in excess of late Paleocene burial, and ∼3,300 Pg C for the critical first 40 kyr of the recovery, primarily located on continental margins. This value is consistent with prior data and model estimates (∼2,000–3,000 Pg C). To reproduce global exogenic δ13C patterns, this Corgburial implies an injection of 5,000–10,000 Pg C during the first ∼100–150 kyr of the PETM, depending on the source's δ13C (−11‰ to −55‰).
Attention‐Based Machine Vision Models and Techniques for Solar Wind Speed Forecasting Using Solar EUV Images
Authors: Brown Edward J. E. , Svoboda Filip , Meredith Nigel P. , Lane Nicholas , Horne Richard B. 
Published: February 2022

AbstractExtreme ultraviolet images taken by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory make it possible to use deep vision techniques to forecast solar wind speed—a difficult, high‐impact, and unsolved problem. At a 4 day time horizon, this study uses attention‐based models and a set of methodological improvements to deliver an 11.1% lower RMSE and a 17.4% higher prediction correlation compared to the previous work testing on the period from 2010 to 2018. Our analysis shows that attention‐based models combined with our pipeline consistently outperform convolutional alternatives. Our study shows a large performance improvement by using a 30 min as opposed to a daily sampling frequency. Our model has learned relationships between coronal holes' characteristics and the speed of their associated high‐speed streams, agreeing with empirical results. Our study finds a strong dependence of our best model on the phase of the solar cycle, with the best performance occurring in the declining phase.
Integrated microfluidic single-cell immunoblotting chip enables high-throughput isolation, enrichment and direct protein analysis of circulating tumor cells
Authors: Abdulla Aynur , Zhang Ting , Li Shanhe , Guo Wenke , Warden Antony R. , Xin Yufang , Maboyi Nokuzola , Lou Jiatao , Xie Haiyang , Ding Xianting 
Published: February 2022

AbstractEffective capture and analysis of a single circulating tumor cell (CTC) is instrumental for early diagnosis and personalized therapy of tumors. However, due to their extremely low abundance and susceptibility to interference from other cells, high-throughput isolation, enrichment, and single-cell-level functional protein analysis of CTCs within one integrated system remains a major challenge. Herein, we present an integrated multifunctional microfluidic system for highly efficient and label-free CTC isolation, CTC enrichment, and single-cell immunoblotting (ieSCI). The ieSCI-chip is a multilayer microfluidic system that combines an inertia force-based cell sorter with a membrane filter for label-free CTC separation and enrichment and a thin layer of a photoactive polyacrylamide gel with microwell arrays at the bottom of the chamber for single-cell immunoblotting. The ieSCI-chip successfully identified a subgroup of apoptosis-negative (Bax-negative) cells, which traditional bulk analysis did not detect, from cisplatin-treated cells. Furthermore, we demonstrated the clinical application of the ieSCI-chip with blood samples from breast cancer patients for personalized CTC epithelial-to-mesenchymal transition (EMT) analysis. The expression level of a tumor cell marker (EpCAM) can be directly determined in isolated CTCs at the single-cell level, and the therapeutic response to anticancer drugs can be simultaneously monitored. Therefore, the ieSCI-chip provides a promising clinical translational tool for clinical drug response monitoring and personalized regimen development.
Deubiquitylase OTUD6B stabilizes the mutated pVHL and suppresses cell migration in clear cell renal cell carcinoma
Authors: Guo Kai , Wei Yinghua , Wang Ze , Zhang Xiaoli , Zhang Xin , Liu Xinxin , Wu Wenyong , Wu Zhengsheng , Zhang Lingqiang , Cui Chun-Ping 
Published: February 2022

AbstractVon Hippel-Lindau (VHL) is an important tumor suppressor, and its inactivation is a hallmark of inherited VHL disease and most sporadic clear cell renal cell carcinoma (ccRCC). VHL protein (pVHL) with missense point mutations are unstable and degraded by the proteasome because of the disruption of elongin binding. Deubiquitylase ovarian tumor domain-containing 6B (OTUD6B) had been documented to couple pVHL and elongin B to form stable VHL - elonginB - elonginC complex, which protects pVHL from degradation. However, whether OTUD6B governs the stability of pVHL wild type and the missense mutants in ccRCC remains largely elusive. Here, we reported that low OTUD6B level predicted poorer survival in ccRCC patients with VHL missense mutation, but not frameshift deletion and nonsense mutation. OTUD6B is able to interact with wild type pVHL and tumor-derived pVHL missense mutants, except for pVHL I151T, and decrease their ubiquitylation and proteasomal degradation in ccRCC cells. Functionally, we revealed that OTUD6B depletion enhanced cell migration and HIF-2α level in ccRCC cells in a pVHL dependent manner. In addition, OTUD6B depletion reduced the inhibitory effects of ectopic pVHL missense mutants on cell migration and HIF-2α level, except for pVHL I151T. Thus, we speculated that I151 residue might be one of key sites of pVHL binding to OTUD6B. These results suggested that OTUD6B is an important regulator for the stability of pVHL missense mutants, which provides a potential therapeutic strategy for ccRCC with VHL mutations.
Long non-coding RNA PAARH promotes hepatocellular carcinoma progression and angiogenesis via upregulating HOTTIP and activating HIF-1α/VEGF signaling
Authors: Wei Huamei , Xu Zuoming , Chen Liucui , Wei Qing , Huang Zihua , Liu Guoman , Li Wenchuan , Wang Jianchu , Tang Qianli , Pu Jian 
Published: February 2022

AbstractHepatocellular carcinoma (HCC) is one of the leading lethal malignancies and a hypervascular tumor. Although some long non-coding RNAs (lncRNAs) have been revealed to be involved in HCC. The contributions of lncRNAs to HCC progression and angiogenesis are still largely unknown. In this study, we identified a HCC-related lncRNA, CMB9-22P13.1, which was highly expressed and correlated with advanced stage, vascular invasion, and poor survival in HCC. We named this lncRNA Progression and Angiogenesis Associated RNA in HCC (PAARH). Gain- and loss-of function assays revealed that PAARH facilitated HCC cellular growth, migration, and invasion, repressed HCC cellular apoptosis, and promoted HCC tumor growth and angiogenesis in vivo. PAARH functioned as a competing endogenous RNA to upregulate HOTTIP via sponging miR-6760-5p, miR-6512-3p, miR-1298-5p, miR-6720-5p, miR-4516, and miR-6782-5p. The expression of PAARH was significantly positively associated with HOTTIP in HCC tissues. Functional rescue assays verified that HOTTIP was a critical mediator of the roles of PAARH in modulating HCC cellular growth, apoptosis, migration, and invasion. Furthermore, PAARH was found to physically bind hypoxia inducible factor-1 subunit alpha (HIF-1α), facilitate the recruitment of HIF-1α to VEGF promoter, and activate VEGF expression under hypoxia, which was responsible for the roles of PAARH in promoting angiogenesis. The expression of PAARH was positively associated with VEGF expression and microvessel density in HCC tissues. In conclusion, these findings demonstrated that PAARH promoted HCC progression and angiogenesis via upregulating HOTTIP and activating HIF-1α/VEGF signaling. PAARH represents a potential prognostic biomarker and therapeutic target for HCC.
Modulation of Hippo signaling by Mnat9 N-acetyltransferase for normal growth and tumorigenesis in Drosophila
Authors: Mok Jung-Wan , Choi Kwang-Wook 
Published: February 2022

AbstractHippo signaling is a conserved mechanism for controlling organ growth. Increasing evidence suggests that Hippo signaling is modulated by various cellular factors for normal development and tumorigenesis. Hence, identification of these factors is pivotal for understanding the mechanism for the regulation of Hippo signaling. Drosophila Mnat9 is a putative N-acetyltransferase that is required for cell survival by affecting JNK signaling. Here we show that Mnat9 is involved in the negative regulation of Hippo signaling. RNAi knockdown of Mnat9 in the eye disc suppresses the rough eye phenotype of overexpressing Crumbs (Crb), an upstream factor of the Hippo pathway. Conversely, Mnat9 RNAi enhances the eye phenotype caused by overexpressing Expanded (Ex) or Warts (Wts) that acts downstream to Crb. Similar genetic interactions between Mnat9 and Hippo pathway genes are found in the wing. The reduced wing phenotype of Mnat9 RNAi is suppressed by overexpression of Yorkie (Yki), while it is suppressed by knockdown of Hippo upstream factors like Ex, Merlin, or Kibra. Mnat9 co-immunoprecipitates with Mer, implying their function in a protein complex. Furthermore, Mnat9 overexpression together with Hpo knockdown causes tumorous overgrowth in the abdomen. Our data suggest that Mnat9 is required for organ growth and can induce tumorous growth by negatively regulating the Hippo signaling pathway.
BMI1 nuclear location is critical for RAD51-dependent response to replication stress and drives chemoresistance in breast cancer stem cells
Authors: Azzoni Violette , Wicinski Julien , Macario Manon , Castagné Martin , Finetti Pascal , Ambrosova Katerina , Rouault Célia D. , Sergé Arnaud , Farina Anne , Agavnian Emilie , Coslet Sergiu , Josselin Emmanuelle , Guille Arnaud , Adelaide José , Zacharioudakis Emmanouil , Castellano Rémy , Bertucci Francois , Birnbaum Daniel , Rodriguez Raphael , Charafe-Jauffret Emmanuelle , Ginestier Christophe 
Published: February 2022

AbstractReplication stress (RS) has a pivotal role in tumor initiation, progression, or therapeutic resistance. In this study, we depicted the mechanism of breast cancer stem cells’ (bCSCs) response to RS and its clinical implication. We demonstrated that bCSCs present a limited level of RS compared with non-bCSCs in patient samples. We described for the first time that the spatial nuclear location of BMI1 protein triggers RS response in breast cancers. Hence, in bCSCs, BMI1 is rapidly located to stalled replication forks to recruit RAD51 and activate homologous-recombination machinery, whereas in non-bCSCs BMI1 is trapped on demethylated 1q12 megasatellites precluding effective RS response. We further demonstrated that BMI1/RAD51 axis activation is necessary to prevent cisplatin-induced DNA damage and that treatment of patient-derived xenografts with a RAD51 inhibitor sensitizes tumor-initiating cells to cisplatin. The comprehensive view of replicative-stress response in bCSC has profound implications for understanding and improving therapeutic resistance.
The feedback loop of ANKHD1/lncRNA MALAT1/YAP1 strengthens the radioresistance of CRC by activating YAP1/AKT signaling
Authors: Yao Ping-an , Wu Yong , Zhao Kui , Li Yecheng , Cao Jianping , Xing Chungen 
Published: February 2022

AbstractInnate radioresistance substantially limits the effectiveness of radiotherapy for colorectal cancer (CRC); thus, a strategy to enhance the radiosensitivity of CRC is urgently needed. Herein, we reported that ankyrin repeat and KH domain containing 1 (ANKHD1) serves as a key regulator of radioresistance in CRC. ANKHD1 was highly expressed in CRC tissues and was highly correlated with Yes-associated protein 1 (YAP1) in CRC. Our results first revealed that ANKHD1 knockdown could increase the radiosensitivity of CRC by regulating DNA-damage repair, both in vitro and in vivo. Furthermore, the interactive regulation between ANKHD1 or YAP1 and lncRNA MALAT1 was revealed by RIP and RNA pull-down assays. Moreover, our results also demonstrated that MALAT1 silencing can radiosensitize CRC cells to IR through YAP1/AKT axis, similar to ANKHD1 silencing. Taken together, we report a feedback loop of ANKHD1/MALAT1/YAP1 that synergistically promotes the transcriptional coactivation of YAP1 and in turn enhances the radioresistance of CRC by regulating DNA-damage repair, probably via the YAP1/AKT axis. Our results suggested that targeting the YAP1/AKT axis downstream of ANKHD1/MALAT1/YAP1 may enhance the radiosensitivity of CRC.
Mesencephalic astrocyte-derived neurotrophic factor reprograms macrophages to ameliorate acetaminophen-induced acute liver injury via p38 MAPK pathway
Authors: Hou Xin , Liu Qi , Gao Yimin , Yong Liang , Xie Huiyuan , Li Wenting , Zhou Yuping , Liu Jun , Feng Lijie , Xu Long , Shen Yuxian , Wang Hua 
Published: February 2022

AbstractAcetaminophen (APAP)-induced liver injury (AILI) is the most frequent cause of acute liver failure; but the underlying mechanisms still remain obscure. Macrophages and endoplasmic reticulum (ER) stress play an important role in the pathogenesis of AILI. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a newly identified 18-kDa soluble protein, whose expression and secretion are stimulated by ER stress. To investigate the role of myeloid cell MANF in the pathogenesis of AILI, we assayed serum and liver samples from AILI model mice and patients with drug-induced liver injury (DILI). We demonstrated that the levels of MANF were elevated in patients with DILI and in mice with AILI. Moreover, myeloid-specific MANF knockout mice were generated and used. It was observed that a delayed liver recovery from myeloid-specific MANF gene knockout mice following APAP overdose compared to that from wild-type mice. MANF deficiency in myeloid cells resulted in increased infiltrating monocyte-derived macrophages (MoMFs) but reduced restorative Ly6Clow macrophages after APAP treatment. MANF supplementation increased restorative Ly6Clow macrophages and subsequently alleviated liver injury. Moreover, MANF could enhance IL-10 expression and phagocytosis in macrophages via p38 MAPK pathway. Altogether, MANF seems to be a critical immune modulator in promoting liver repair via reducing and reprogramming MoMFs. MANF perhaps promoted the phenotype conversion of pro-inflammatory MoMFs to pro-restorative Ly6Clow MoMFs via p38 MAPK pathway, particularly through enhancing IL-10 and phagocytosis.
NR4A1 promotes LEF1 expression in the pathogenesis of papillary thyroid cancer
Authors: Jiang Cen , He Jianli , Xu Sunwang , Wang Qi , Cheng Jinke 
Published: February 2022

AbstractThe morbidity of papillary thyroid cancer (PTC) is on the rise, but its pathogenesis is still poorly understood. NR4A1 is a transcription factor primarily involving a wide range of pathophysiological responses, but its relationship with PTC malignancy remains unclear. This study demonstrates that high NR4A1 expression is strongly associated with poor survival outcomes in PTC patients. The depletion of NR4A1 significantly inhibited the proliferation of PTC cells by negating the LEF1-mediated oncogenic alteration. Mechanistically, NR4A1 directly binds to the promoter region of LEF1 and leads to crosstalk with histone acetylation and DNA demethylation to transcriptionally upregulate LEF1 expression, subsequently promoting downstream growth-related genes expressions in PTC. In the light of our findings, NR4A1 may be an emerging driving factor in PTC pathogenesis and progression.
Constitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate
Authors: Parichha Arpan , Suresh Varun , Chatterjee Mallika , Kshirsagar Aditya , Ben-Reuven Lihi , Olender Tsviya , Taketo M. Mark , Radosevic Velena , Bobic-Rasonja Mihaela , Trnski Sara , Holtzman Michael J. , Jovanov-Milosevic Nataša , Reiner Orly , Tole Shubha 
Published: February 2022

AbstractThe choroid plexus secretes cerebrospinal fluid and is critical for the development and function of the brain. In the telencephalon, the choroid plexus epithelium arises from the Wnt- expressing cortical hem. Canonical Wnt signaling pathway molecules such as nuclear β-CATENIN are expressed in the mouse and human embryonic choroid plexus epithelium indicating that this pathway is active. Point mutations in human β-CATENIN are known to result in the constitutive activation of canonical Wnt signaling. In a mouse model that recapitulates this perturbation, we report a loss of choroid plexus epithelial identity and an apparent transformation of this tissue to a neuronal identity. Aspects of this phenomenon are recapitulated in human embryonic stem cell derived organoids. The choroid plexus is also disrupted when β-Catenin is conditionally inactivated. Together, our results indicate that canonical Wnt signaling is required in a precise and regulated manner for normal choroid plexus development in the mammalian brain.
Buxus and Tetracentron genomes help resolve eudicot genome history
Authors: Chanderbali Andre S. , Jin Lingling , Xu Qiaoji , Zhang Yue , Zhang Jingbo , Jian Shuguang , Carroll Emily , Sankoff David , Albert Victor A. , Howarth Dianella G. , Soltis Douglas E. , Soltis Pamela S. 
Published: February 2022

AbstractAncient whole-genome duplications (WGDs) characterize many large angiosperm lineages, including angiosperms themselves. Prominently, the core eudicot lineage accommodates 70% of all angiosperms and shares ancestral hexaploidy, termed gamma. Gamma arose via two WGDs that occurred early in eudicot history; however, the relative timing of these is unclear, largely due to the lack of high-quality genomes among early-diverging eudicots. Here, we provide complete genomes for Buxus sinica (Buxales) and Tetracentron sinense (Trochodendrales), representing the lineages most closely related to core eudicots. We show that Buxus and Tetracentron are both characterized by independent WGDs, resolve relationships among early-diverging eudicots and their respective genomes, and use the RACCROCHE pipeline to reconstruct ancestral genome structure at three key phylogenetic nodes of eudicot diversification. Our reconstructions indicate genome structure remained relatively stable during early eudicot diversification, and reject hypotheses of gamma arising via inter-lineage hybridization between ancestral eudicot lineages, involving, instead, only stem lineage core eudicot ancestors.
Immunomodulatory matrix-bound nanovesicles mitigate acute and chronic pristane-induced rheumatoid arthritis
Authors: Crum Raphael J. , Hall Kelsey , Molina Catalina Pineda , Hussey George S. , Graham Emma , Li Hongshuai , Badylak Stephen F. 
Published: February 2022

AbstractRheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and destruction of synovial joints affecting ~7.5 million people worldwide. Disease pathology is driven by an imbalance in the ratio of pro-inflammatory vs. anti-inflammatory immune cells, especially macrophages. Modulation of macrophage phenotype, specifically an M1 to M2, pro- to anti-inflammatory transition, can be induced by biologic scaffold materials composed of extracellular matrix (ECM). The ECM-based immunomodulatory effect is thought to be mediated in part through recently identified matrix-bound nanovesicles (MBV) embedded within ECM. Isolated MBV was delivered via intravenous (i.v.) or peri-articular (p.a.) injection to rats with pristane-induced arthritis (PIA). The results of MBV administration were compared to intraperitoneal (i.p.) administration of methotrexate (MTX), the clinical standard of care. Relative to the diseased animals, i.p. MTX, i.v. MBV, and p.a. MBV reduced arthritis scores in both acute and chronic pristane-induced arthritis, decreased synovial inflammation, decreased adverse joint remodeling, and reduced the ratio of synovial and splenic M1 to M2 macrophages (p < 0.05). Both p.a. and i.v. MBV reduced the serum concentration of RA and PIA biomarkers CXCL10 and MCP-3 in the acute and chronic phases of disease (p < 0.05). Flow-cytometry revealed the presence of a systemic CD43hi/His48lo/CD206+, immunoregulatory monocyte population unique to p.a. and i.v. MBV treatment associated with disease resolution. The results show that the therapeutic efficacy of MBV is equal to that of MTX for the management of acute and chronic pristane-induced arthritis and, further, this effect is associated with modulation of local synovial macrophages and systemic myeloid populations.