bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying the Effects of Non‐Hydrostatic Stress on Single‐Component Polymorphs
Authors: Hess Benjamin L. , Ague Jay J. 
Published: April 2021

AbstractGibbs free energy, the fundamental thermodynamic potential used to calculate equilibrium mineral assemblages in geological systems, does not apply to non‐hydrostatically stressed solids. Consequently, there is debate over the significance of non‐hydrostatic stress in petrological and geophysical processes. To help resolve this debate, we consider the effects of non‐hydrostatic stress on the polymorph pairs kyanite/sillimanite, graphite/diamond, calcite/aragonite, and quartz/coesite. While these polymorphs are most relevant to metamorphic processes, the concepts developed are applicable to any single‐component solid reaction. We quantitatively show how stress variations normal to an interface alter equilibrium temperatures of polymorph pairs by approximately two orders of magnitude more than stress variations parallel to an interface. Thus, normal stress controls polymorph stability to first order. High‐pressure polymorphs are expected to preferentially nucleate normal to and grow parallel to the maximum stress and low‐pressure polymorphs, the minimum stress. Nonetheless, stress variations parallel to an interface allow for the surprising possibility that a high‐pressure polymorph can become more stable relative to a low‐pressure polymorph as stress decreases. The effects of non‐hydrostatic stress on mineral equilibrium are unlikely to be observed in systems with interconnected, fluid‐filled porosity, as fluid‐mediated reactions yield mineral assemblages at approximately constant pressures. In dry systems, however, reactions can occur directly between elastic solids, facilitating the direct application of non‐hydrostatic thermodynamics. Non‐hydrostatic stress is likely to be important to the evolution of metamorphic systems, as preferential orientations of polymorphic reactions can generate seismicity and may influence fundamental rock properties such as porosity and seismic anisotropy.
Nature, Origin, and Evolution of the Pyrenean‐Cantabrian Junction
Authors: Lescoutre R. , Manatschal G. , Muñoz J. A. 
Published: April 2021

AbstractWe investigate the present‐day orogenic architecture of the Pyrenean‐Cantabrian junction corresponding to a boundary between inverted rift segments using seismic interpretation, field data, and borehole information. This junction was formerly attributed to a major NNE‐SSW striking Pamplona transfer fault segmenting the Basque‐Cantabrian and Mauléon basins during both rifting and convergence. Our study shows that the orogenic architecture results from a strong decoupling between the thick‐skinned (basement‐involved) and the thin‐skinned (detached in the Upper Triassic evaporites) modes of deformation. The evaporites decoupling horizon was responsible for the transport and allochthony of the former rift basins over large distances on top of the Basque massifs and the Ebro and Aquitaine foreland basins. A crustal‐scale cross‐section depicts the allochthony of the Basque massifs forming a crustal wedge over the crusts of Iberian, Ebro, and Eurasian affinity. Three‐dimensional analysis of the present‐day architecture suggests that two phases of rifting and related basins can be recognized: the Late Jurassic‐Barremian and the Aptian‐Cenomanian basins. Furthermore, we show that during the Aptian‐Cenomanian, the Mauléon and Basque‐Cantabrian rift segments spatially overlapped north and south of the Basque massifs and were controlled by WNW‐ESE striking extensional faults. These results discard the existence of a major Pamplona transfer fault and argue for NNE‐SSW direction of extension during the mid‐Cretaceous. This study emphasizes the role of inheritance during rifting and reactivation and provides a new syn‐rift template, which controlled the Alpine reactivation. Finally, these results have major implications for the Iberia‐Eurasia plate boundary and the kinematics of the North Pyrenean basins.
The Role of Shortening in the Sevier Hinterland Within the U.S. Cordilleran Retroarc Thrust System: Insights From the Cretaceous Newark Canyon Formation in Central Nevada
Authors: Di Fiori Russell V. , Long Sean P. , Fetrow Anne C. , Snell Kathryn E. , Bonde Joshua W. , Vervoort Jeff D. 
Published: April 2021

AbstractDocumenting the spatio‐temporal progression of deformation within fold‐thrust belts is critical for understanding orogen dynamics. In the North American Cordillera, the geometry, magnitude, and timing of contractional deformation across a broad region of Nevada known as the “Sevier hinterland” has been difficult to characterize due to minimal exposures of syn‐contractional sedimentary rocks and overprinting of Cenozoic extension. To address this, we present geologic mapping and U‐Pb zircon geochronology from three exposures of the Cretaceous Newark Canyon Formation (NCF) in central Nevada. In the Cortez Mountains, NCF deposition between ∼119 and 110 Ma is hypothesized to be related to generation of relief by thrusting/folding to the west. In the Fish Creek Range, NCF deposition between ∼130 and 100 Ma was related to motion on an east‐vergent thrust fault. In the Pancake Range, NCF deposition is bracketed between ∼129 and 66 Ma and post‐dated east‐vergent folding. We incorporate these timing constraints into a compilation of deformation timing in the Sevier hinterland. Late Jurassic (∼165 and 155 Ma) shortening, which is largely post‐dated shortening in the Luning‐Fencemaker thrust belt to the west and pre‐dated initial deformation in the Sevier fold‐thrust belt to the east, is interpreted to represent diffuse, low‐magnitude deformation that accompanied eastward propagation of the basal Cordilleran décollement. Cretaceous (∼130 and 75 Ma) hinterland shortening, which includes deformation associated with NCF deposition, was contemporaneous with shortening in the Sevier fold‐thrust belt. This is interpreted to represent long‐duration strain partitioning between the foreland and hinterland during continued coupling above the basal décollement and the progressive westward underthrusting of thick North American lower‐middle crust.
Statistical Modeling of the Bering Strait Throughflow for Operational Sea Ice Forecasting in the Chukchi Sea
Authors: Lenetsky Jed E. , Serreze Mark C. 
Published: April 2021

AbstractWe utilize statistically modeled ocean heat transports through the Bering Strait along with additional predictors to create skillful predictions of sea ice retreat and advance dates in the Chukchi Sea. Interannual variability of June and September oceanic heat transports through the strait can be captured using modeled Ekman transports, surface winds, and sea surface temperatures. At one‐month leads, our models can explain 41% and 79% of sea ice retreat and advance date variance with root mean squared errors (RMSEs) of 10.2 and 12.8 days respectively. At 4‐month leads, our models can respectively capture 37% and 73% of sea ice retreat and advance date variance with RMSEs of 8.5 and 14.6 days. These findings offer a path toward operational forecasts of sea ice retreat and advance dates in the Chukchi Sea in the absence of direct, readily available observations of heat transports in the strait.
A Morphodynamic Model to Evaluate Long‐Term Sandbar Rebuilding Using Controlled Floods in the Grand Canyon
Authors: Mueller Erich R. , Grams Paul E. 
Published: April 2021

AbstractControlled floods released from dams have become a common restoration strategy in river systems worldwide. Here we present a morphodynamic model of sandbar volume change for a subset of sandbars of the Colorado River in Grand Canyon National Park, where controlled floods are part of a management strategy focused on sandbar maintenance. We simulate sandbars as a triangular wedge, where deposition and erosion are modeled using physically based approaches that are driven by nearly continuous observations of flow and suspended sand concentration. We optimize an eddy exchange coefficient and erosion rate parameter by comparing model predictions to measured bar volumes. The model captures most of the variability in observed volume changes, and demonstrates the importance of flood frequency and sand concentration on average bar size. The model is easily implemented and adaptable, providing a means for predicting the future behavior of sandbars under a variety of streamflow and sediment supply scenarios.
Sulfide Dissolution and Awaruite Formation in Continental Serpentinization Environments and Its Implications to Supporting Life
Authors: Schwarzenbach E. M. , Vrijmoed J. C. , Engelmann J. M. , Liesegang M. , Wiechert U. , Rohne R. , Plümper O. 
Published: April 2021

AbstractSerpentinization environments are key locations that support microbial communities by the abiogenic formation of reduced species associated with peridotite alteration. Here we studied partially serpentinized peridotites from the Chimaera seeps (Turkey), an active continental serpentinization system that vents highly methane‐rich fluids, to investigate the impact of water‐rock interaction on the sulfide and metal mineralogy and its implications on supporting microbial communities. Using high‐resolution scanning electron microscopy, electron microprobe analysis, and transmission electron microscopy we found diverse pentlandite decomposition features with precipitation of secondary sulfides including millerite, heazlewoodite, as well as Cu‐bearing sulfides, native Cu, and awaruite (Ni3Fe). Awaruite forms dense veinlets to single crystal platelets tens of nanometers in size, which is formed by desulphurization of pentlandite. In addition, the nanometer‐sized awaruite platelets are intimately intergrown with serpentine suggesting its growth during peridotite alteration by a dissolution‐precipitation process, likely associated with the interaction of methane‐ and H2‐rich but highly sulfur‐undersaturated fluids. Based on sulfur isotope signatures we infer a mantle and mid‐ocean ridge origin of the sulfide minerals associated with the first stage of partial serpentinization and awaruite formation. Subsequent and ongoing continental fluid‐rock interaction causes significant sulfide decomposition resulting in the formation of porosity and the release of, amongst others, H2S and Fe. These species may likely provide a source of nutrients for active microbial communities in these comparatively nutrient‐starved, low‐temperature continental serpentinization environments.
The metastasis suppressor protein NM23-H1 modulates the PI3K-AKT axis through interaction with the p110α catalytic subunit
Authors: Pennino Francesco Paolo , Murakami Masanao , Zollo Massimo , Robertson Erle S. 
Published: April 2021

AbstractThe PI3K pathway is one of the most deregulated pathways in cancer, which is predominantly due to gain of function mutations or altered expression of the PI3KCA gene. This is codified by what is seen for the class I PI3K catalytic subunit p110α, a common feature of many cancers. The metastasis suppressor protein NM23-H1 (NME1), whose ability to suppress the metastasis activities of different tumors has been widely described and was previously reported to alter phosphatidylinositol signaling. Here, we show interaction of NM23-H1 with the p110α subunit and the functional consequence of this interaction. This interaction is predominantly localized at the plasma membrane with some signals seen in the cytoplasmic compartment. Analysis of NM23-H1 levels showed a negative correlation between NM23-H1 expression and Akt phosphorylation, the key marker of PI3K pathway activation. Investigating the functional consequence of this interaction using cell motility and clonogenicity assays showed that expression of NM23-H1 reversed the enhanced migration, invasion, adhesion, and filopodia structure formation in cells expressing the p110α catalytic subunit. A similar trend was seen in anchorage-independent assays. Notably, differential analyses using NM23-H1 mutants which lacked the enzymatic and metastasis suppressor activity, showed no detectable interaction between p110α and the NM23-H1 mutant proteins P96S, H118F, and S120G, as well as no dysregulation of the PI3K-AKT axis.
Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications
Authors: Salvetat Nicolas , Chimienti Fabrice , Cayzac Christopher , Dubuc Benjamin , Checa-Robles Francisco , Dupre Pierrick , Mereuze Sandie , Patel Vipul , Genty Catherine , Lang Jean-Philippe , Pujol Jean-François , Courtet Philippe , Weissmann Dinah 
Published: April 2021

AbstractMental health issues, including major depressive disorder, which can lead to suicidal behavior, are considered by the World Health Organization as a major threat to global health. Alterations in neurotransmitter signaling, e.g., serotonin and glutamate, or inflammatory response have been linked to both MDD and suicide. Phosphodiesterase 8A (PDE8A) gene expression is significantly decreased in the temporal cortex of major depressive disorder (MDD) patients. PDE8A specifically hydrolyzes adenosine 3′,5′-cyclic monophosphate (cAMP), which is a key second messenger involved in inflammation, cognition, and chronic antidepressant treatment. Moreover, alterations of RNA editing in PDE8A mRNA has been described in the brain of depressed suicide decedents. Here, we investigated PDE8A A-to-I RNA editing-related modifications in whole blood of depressed patients and suicide attempters compared to age-matched and sex-matched healthy controls. We report significant alterations of RNA editing of PDE8A in the blood of depressed patients and suicide attempters with major depression, for which the suicide attempt took place during the last month before sample collection. The reported RNA editing modifications in whole blood were similar to the changes observed in the brain of suicide decedents. Furthermore, analysis and combinations of different edited isoforms allowed us to discriminate between suicide attempters and control groups. Altogether, our results identify PDE8A as an immune response-related marker whose RNA editing modifications translate from brain to blood, suggesting that monitoring RNA editing in PDE8A in blood samples could help to evaluate depressive state and suicide risk.
Serum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ASK1-JNK/p38 MAPK pathways
Authors: Chen Xi , Ma Weijie , Yao Ye , Zhang Qi , Li Jinghua , Wu Xiaoling , Mei Chengjie , Jiang Xiang , Chen Yiran , Wang Ganggang , Wang Kunlei , Liu Yingyi , Guo Yonghua , Liu Zhisu , Yuan Yufeng 
Published: April 2021

AbstractSerum deprivation-response protein (SDPR), a phosphatidylserine-binding protein, which is known to have a promising role in caveolar biogenesis and morphology. However, its function in hepatocellular carcinoma (HCC) was still largely unknown. In this study, we discussed the characterization and identification of SDPR, and to present it as a novel apoptosis candidate in the incidence of HCC. We identified 81 HCC cases with lower SDPR expression in the tumor tissues with the help of qRT-PCR assay, and lower SDPR expression was potentially associated with poor prognostication. The phenotypic assays revealed that cell proliferation, invasion, and migration were profoundly connected with SDPR, both in vivo and in vitro. The data obtained from the gene set enrichment analysis (GSEA) carried out on the liver hepatocellular carcinoma (LIHC), and also The Cancer Genome Atlas (TCGA) findings indicated that SDPR was involved in apoptosis and flow cytometry experiments further confirmed this. Furthermore, we identified the interaction between SDPR and apoptosis signal-regulating kinase 1 (ASK1), which facilitated the ASK1 N-terminus-mediated dimerization and increased ASK1-mediated signaling, thereby activating the JNK/p38 mitogen-activated protein kinases (MAPKs) and finally enhanced cell apoptosis. Overall, this work identified SDPR as a tumor suppressor, because it promoted apoptosis by activating ASK1-JNK/p38 MAPK pathways in HCC.
GSTZ1 sensitizes hepatocellular carcinoma cells to sorafenib-induced ferroptosis via inhibition of NRF2/GPX4 axis
Authors: Wang Qiujie , Bin Cheng , Xue Qiang , Gao Qingzhu , Huang Ailong , Wang Kai , Tang Ni 
Published: April 2021

AbstractIncreasing evidence supports that ferroptosis plays an important role in tumor growth inhibition. Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, has been shown to induce ferroptosis in hepatocellular carcinoma (HCC). However, some hepatoma cell lines are less sensitive to sorafenib-induced ferroptotic cell death. Glutathione S-transferase zeta 1 (GSTZ1), an enzyme in the catabolism of phenylalanine, suppresses the expression of the master regulator of cellular redox homeostasis nuclear factor erythroid 2-related factor 2 (NRF2). This study aimed to investigate the role and underlying molecular mechanisms of GSTZ1 in sorafenib-induced ferroptosis in HCC. GSTZ1 was significantly downregulated in sorafenib-resistant hepatoma cells. Mechanistically, GSTZ1 depletion enhanced the activation of the NRF2 pathway and increased the glutathione peroxidase 4 (GPX4) level, thereby suppressing sorafenib-induced ferroptosis. The combination of sorafenib and RSL3, a GPX4 inhibitor, significantly inhibited GSTZ1-deficient cell viability and promoted ferroptosis and increased ectopic iron and lipid peroxides. In vivo, the combination of sorafenib and RSL3 had a synergic therapeutic effect on HCC progression in Gstz1−/− mice. In conclusion, this finding demonstrates that GSTZ1 enhanced sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in HCC cells. Combination therapy of sorafenib and GPX4 inhibitor RSL3 may be a promising strategy in HCC treatment.
POU2F2 regulates glycolytic reprogramming and glioblastoma progression via PDPK1-dependent activation of PI3K/AKT/mTOR pathway
Authors: Yang Rui , Wang Mei , Zhang Guanghui , Li Yanping , Wang Lulin , Cui Hongjuan 
Published: April 2021

AbstractThe POU Class Homeobox 2 (POU2F2) is a member of POU transcription factors family, which involves in cell immune response by regulating B cell proliferation and differentiation genes. Recent studies have shown that POU2F2 acts as tumor-promoting roles in some cancers, but the underlying mechanism remains little known. Here, we identified that the highly expressed POU2F2 significantly correlated with poor prognosis of glioblastoma (GBM) patients. POU2F2 promoted cell proliferation and regulated glycolytic reprogramming. Mechanistically, the AKT/mTOR signaling pathway played important roles in the regulation of POU2F2-mediated aerobic glycolysis and cell growth. Furthermore, we demonstrated that POU2F2 activated the transcription of PDPK1 by directly binding to its promoter. Reconstituted the expression of PDPK1 in POU2F2-knockdown GBM cells reactivated AKT/mTOR pathway and recovered cell glycolysis and proliferation, whereas this effect was abolished by the PDPK1/AKT interaction inhibitor. In addition, we showed that POU2F2-PDPK1 axis promoted tumorigenesis by regulating glycolysis in vivo. In conclusion, our findings indicate that POU2F2 leads a metabolic shift towards aerobic glycolysis and promotes GBM progression in PDPK1-dependent activation of PI3K/AKT/mTOR pathway.
A clinical transcriptome approach to patient stratification and therapy selection in acute myeloid leukemia
Authors: Docking T. Roderick , Parker Jeremy D. K. , Jädersten Martin , Duns Gerben , Chang Linda , Jiang Jihong , Pilsworth Jessica A. , Swanson Lucas A. , Chan Simon K. , Chiu Readman , Nip Ka Ming , Mar Samantha , Mo Angela , Wang Xuan , Martinez-Høyer Sergio , Stubbins Ryan J. , Mungall Karen L. , Mungall Andrew J. , Moore Richard A. , Jones Steven J. M. , Birol İnanç , Marra Marco A. , Hogge Donna , Karsan Aly 
Published: April 2021

AbstractAs more clinically-relevant genomic features of myeloid malignancies are revealed, it has become clear that targeted clinical genetic testing is inadequate for risk stratification. Here, we develop and validate a clinical transcriptome-based assay for stratification of acute myeloid leukemia (AML). Comparison of ribonucleic acid sequencing (RNA-Seq) to whole genome and exome sequencing reveals that a standalone RNA-Seq assay offers the greatest diagnostic return, enabling identification of expressed gene fusions, single nucleotide and short insertion/deletion variants, and whole-transcriptome expression information. Expression data from 154 AML patients are used to develop a novel AML prognostic score, which is strongly associated with patient outcomes across 620 patients from three independent cohorts, and 42 patients from a prospective cohort. When combined with molecular risk guidelines, the risk score allows for the re-stratification of 22.1 to 25.3% of AML patients from three independent cohorts into correct risk groups. Within the adverse-risk subgroup, we identify a subset of patients characterized by dysregulated integrin signaling andRUNX1orTP53mutation. We show that these patients may benefit from therapy with inhibitors of focal adhesion kinase, encoded byPTK2, demonstrating additional utility of transcriptome-based testing for therapy selection in myeloid malignancy.
Cut-like homeobox 1 (CUX1) tumor suppressor gene haploinsufficiency induces apoptosis evasion to sustain myeloid leukemia
Authors: Supper Emmanuelle , Rudat Saskia , Iyer Vivek , Droop Alastair , Wong Kim , Spinella Jean-François , Thomas Patrick , Sauvageau Guy , Adams David J. , Wong Chi C. 
Published: April 2021

AbstractWhile oncogenes promote tumorigenesis, they also induce deleterious cellular stresses, such as apoptosis, that cancer cells must combat by coopting adaptive responses. Whether tumor suppressor gene haploinsufficiency leads to such phenomena and their mechanistic basis is unclear. Here, we demonstrate that elevated levels of the anti-apoptotic factor, CASP8 and FADD-like apoptosis regulator (CFLAR), promotes apoptosis evasion in acute myeloid leukemia (AML) cells haploinsufficient for the cut-like homeobox 1 (CUX1) transcription factor, whose loss is associated with dismal clinical prognosis. Genome-wide CRISPR/Cas9 screening identifies CFLAR as a selective, acquired vulnerability in CUX1-deficient AML, which can be mimicked therapeutically using inhibitor of apoptosis (IAP) antagonists in murine and human AML cells. Mechanistically, CUX1 deficiency directly alleviates CUX1 repression of the CFLAR promoter to drive CFLAR expression and leukemia survival. These data establish how haploinsufficiency of a tumor suppressor is sufficient to induce advantageous anti-apoptosis cell survival pathways and concurrently nominate CFLAR as potential therapeutic target in these poor-prognosis leukemias.