bluuebunny/crossref_metadata_2025_split huggingface dataset:
PWD: A Petrological Workspace and Database tool
Authors: Schonwalder‐Angel Dayana , Albert Helena , Tuan Lam Ngoc , Phi Nguyen Xuan , Utami Sri Budhi , Li Weiran , Khanh Phung Minh , Widiwijayanti Christina , Costa Fidel 
Published: December 2019

AbstractThe Petrology Workspace and Database (PWD; https://petro.wovodat.org) is a web‐based data repository and interface that allows researchers to access, share, store, and manage petrological, mineralogical, and whole rock data in a contextualized manner. The uniqueness of the PWD is that it links images to different types of images and to compositional data providing a powerful visualization and framework of information at a wide range of scales, from the meter‐sized outcrop to a few micrometers of a thin rock section. The PWD archives various data types and formats, and it includes multilevel data sets with an interactive online interface. The database is linked with other databases for volcanic eruptions (Smithsonian' Global Volcanism Program (GVP)) and for whole rock chemistry (EarthChem). The tool has four main features: (1) storage and management of spatial‐referenced data (e.g., from fieldwork notes to lab geochemical analysis); (2) a hierarchical relationship between different types of data using the Workspace interactive tool; (3) graph plots to visualize the data; and (4) the possibility of data sharing in a database structure that is managed by authorization levels. The PWD is a practical and efficient database management system that facilitates effective contextualized data preservation and sharing among scientists. It also can serve as a Data Management Plan and provide a framework for auditing research integrity both of which are becoming the new standards of most funding agencies and journals.©2019. The Authors.
Impact of Iceberg Calving on the Retreat of Thwaites Glacier, West Antarctica Over the Next Century With Different Calving Laws and Ocean Thermal Forcing
Authors: Yu Hongju , Rignot Eric , Seroussi Helene , Morlighem Mathieu , Choi Youngmin 
Published: December 2019

AbstractThwaites Glacier, West Antarctica, has been a major contributor to global sea level rise over the past decades. Prior studies illustrated the critical role of ice shelf melt and iceberg calving based on cliff height in driving the retreat of Thwaites glacier. Here, we simulate its evolution with various calving laws and rates of frontal melt by the ocean in the absence of a buttressing ice shelf. Over the next century, we find that volume losses increase by 15–160% with a von Mises calving law compared to the case where the initial ice shelf is kept and the ice front is fixed at its current position, 10–20% with a buoyancy‐driven calving law, and 5–50% with frontal melt caused by ocean thermal forcing. Bed topography exerts the ultimate control on the evolution of Thwaites. In all simulations, once Thwaites Glacier retreats past the western subglacial ridge, the retreat becomes rapidly unstoppable.
Amplification of Australian Heatwaves via Local Land‐Atmosphere Coupling
Authors: Hirsch Annette L. , Evans Jason P. , Di Virgilio Giovanni , Perkins‐Kirkpatrick Sarah E. , Argüeso Daniel , Pitman Andrew J. , Carouge Claire C. , Kala Jatin , Andrys Julia , Petrelli Paola , Rockel Burkhardt 
Published: December 2019

Key Points

Spatial variability in the land‐atmosphere coupling defines local heatwave sensitivity to antecedent land surface conditions
Land‐driven coupling regions experience a higher heatwave day frequency with temperatures sensitive to prior soil moisture conditions
Antecedent soil moisture anomaly rather than drying rate 2 weeks prior to a heatwave has a longer impact on heatwave temperatures
The Role of Large Woody Debris in Beach‐Dune Interaction
Authors: Grilliot M. J. , Walker I. J. , Bauer B. O. 
Published: December 2019

AbstractCoastal foredune evolution involves complex processes and controls that result from the interaction of aeolian and nearshore dynamics. No studies to date have quantified and examined the role of large woody debris (LWD) as a modulator of sediment delivery across the backshore and as a control on foredune development and maintenance. Results from a 4‐year research initiative on a high‐energy, macrotidal beach, and foredune system show that storm events lead to wave‐induced erosion of the backshore and consequent reworking of the LWD matrix. The exposed LWD matrix subsequently traps wind‐blown sand on the upper beach, reducing sediment delivery to the foredune by 99% in some cases. In turn, deposition within the LWD matrix leads to rapid burial of the LWD, at least until the next reworking or dune erosion event occurs. Interannual observations at this site indicate that infilling of the accommodation space within the LWD matrix can be rapid, so sediment starvation of the foredune is typically a relatively short‐lived phase. This suggests that that the LWD matrix is a highly effective, yet ephemeral, sand‐trapping reservoir. Critical to these interactions is the frequency and magnitude of nearshore events that erode the beach periodically and reorganize the LWD matrix, which directly impacts the ability of LWD to modulate onshore sand transport to the foredune, store sediment in the backshore, and act as a buffer against erosive events. An empirically derived conceptual model explaining these relationships is presented.
Next‐Generation Biomass Mapping for Regional Emissions and Carbon Inventories: Incorporating Uncertainty in Wildland Fuel Characterization
Authors: Prichard Susan J. , Kennedy Maureen C. , Andreu Anne G. , Eagle Paige C. , French Nancy H. , Billmire Michael 
Published: December 2019

AbstractBiomass mapping is used in variety of applications including carbon assessments, emission inventories, and wildland fire and fuel planning. Single values are often applied to individual pixels to represent biomass of classified vegetation, but each biomass estimate has associated uncertainty that is generally not acknowledged nor quantified. In this study, we developed a geospatial database of wildland fuel biomass values to characterize the inherent variability within and across major vegetation types of the United States and Canada. For vegetation types that had sufficient quantification of biomass by fuel type (e.g., canopy, shrub, herbaceous, fine downed wood, coarse downed wood, and organic soil layers), we developed empirical distribution estimates. Based on available data, fitted distributions will be useful for informing the first‐generation biomass mapping that incorporates variability in loading by vegetation and fuel type and to evaluate potential errors in point estimates given in current map products. Because combustible biomass is a common input in fire and smoke models, variability estimated for fitted distributions can be used to inform data input uncertainty in predictions of wildland fuel consumption and emissions and to provide stochastic inputs of biomass to ensemble simulation models.
Excess Nitrate Export in Mountaintop Removal Coal Mining Watersheds
Authors: Brooks Alexander C. , Ross Matthew R. V. , Nippgen Fabian , McGlynn Brian L. , Bernhardt Emily S. 
Published: December 2019

AbstractThroughout the Central Appalachian ecoregion, mountaintop removal coal mining (MTM) is the predominant form of land use change. The streams draining MTM impacted watersheds have been reported to contain high stream nitrate (NO3−) concentrations, yet the source and persistence of elevated NO3−remains unknown. Here we compiled data from multiple sources to conduct a regional evaluation of the impact of mining on stream NO3−, examine NO3−persistence after mining cessation, and identify potential N sources. Using water quality data from six large watersheds, we observe elevated NO3−in watersheds with the highest active mining density. At four small MTM watersheds with repeat sampling, we found that high levels of NO3−concentrations declined after mining cessation but remain elevated above reference after several decades. At MTM watersheds, we found annual mass flux of NO3−was 3.68 to 26.4 kg N ha−1year−1, which is 1 to 2 orders of magnitude higher than a nearby forested reference watershed. Stream water NO3−isotopic ratios at these sites did not match previously suggested NO3−sources such as explosives used during mining and fertilizer applied during reclamation but were highly enriched in both δ15N and δ18O compared to the reference watershed suggesting high rates of NO3−retention. Explosive residue could account for the bulk of watershed NO3−export during active mining phases but other mining related N sources including fertilizer and rock‐derived N, the construction of valley fills, and alterations in watershed NO3‐cycling likely contribute to the persistence of elevated NO3−export observed in this study.
GABPA is a master regulator of luminal identity and restrains aggressive diseases in bladder cancer
Authors: Guo Yanxia , Yuan Xiaotian , Li Kailin , Dai Mingkai , Zhang Lu , Wu Yujiao , Sun Chao , Chen Yuan , Cheng Guanghui , Liu Cheng , Strååt Klas , Kong Feng , Zhao Shengtian , Bjorkhölm Magnus , Xu Dawei 
Published: December 2019

Abstract
TERT promoter mutations occur in the majority of glioblastoma, bladder cancer (BC), and other malignancies while the ETS family transcription factors GABPA and its partner GABPB1 activate the mutant TERT promoter and telomerase in these tumors. GABPA depletion or the disruption of the GABPA/GABPB1 complex by knocking down GABPB1 was shown to inhibit telomerase, thereby eliminating the tumorigenic potential of glioblastoma cells. GABPA/B1 is thus suggested as a cancer therapeutic target. However, it is unclear about its role in BC. Here we unexpectedly observed that GABPA ablation inhibited TERT expression, but robustly increased proliferation, stem, and invasive phenotypes and cisplatin resistance in BC cells, while its overexpression exhibited opposite effects, and inhibited in vivo metastasizing in a xenograft transplant model. Mechanistically, GABPA directly activates the transcription of FoxA1 and GATA3, key transcription factors driving luminal differentiation of urothelial cells. Consistently, TCGA/GEO dataset analyses show that GABPA expression is correlated positively with luminal while negatively with basal signatures. Luminal tumors express higher GABPA than do basal ones. Lower GABPA expression is associated with the GABPA gene methylation or deletion (especially in basal subtype of BC tumors), and predicted significantly shorter patient survival based on TCGA and our cohort of BC patient analyses. Taken together, GABPA dictates luminal identity of BC cells and inhibits aggressive diseases in BC by promoting cellular differentiation despite its stimulatory effect on telomerase/TERT activation. Given these biological functions and its frequent methylation and/or deletion, GABPA serves as a tumor suppressor rather than oncogenic factor in BC. The GABPA effect on oncogenesis is context-dependent and its targeting for telomerase inhibition in BC may promote disease metastasizing.
USP22-dependent HSP90AB1 expression promotes resistance to HSP90 inhibition in mammary and colorectal cancer
Authors: Kosinsky Robyn Laura , Helms Marlena , Zerche Maria , Wohn Luisa , Dyas Anna , Prokakis Evangelos , Kazerouni Zahra Basir , Bedi Upasana , Wegwitz Florian , Johnsen Steven A. 
Published: December 2019

AbstractAs a member of the 11-gene “death-from-cancer” gene expression signature, overexpression of the Ubiquitin-Specific Protease 22 (USP22) was associated with poor prognosis in various human malignancies. To investigate the function of USP22 in cancer development and progression, we sought to detect common USP22-dependent molecular mechanisms in human colorectal and breast cancer cell lines. We performed mRNA-seq to compare gene expression profiles of various colorectal (SW837, SW480, HCT116) and mammary (HCC1954 and MCF10A) cell lines upon siRNA-mediated knockdown of USP22. Intriguingly, while USP22 depletion had highly heterogeneous effects across the cell lines, all cell lines displayed a common reduction in the expression of Heat Shock Protein 90 Alpha Family Class B Member 1 (HSP90AB1). The downregulation of HSP90AB1 was confirmed at the protein level in these cell lines as well as in colorectal and mammary tumors in mice with tissue-specific Usp22 deletions. Mechanistically, we detected a significant reduction of H3K9ac on the HSP90AB1 gene in USP22-deficient cells. Interestingly, USP22-deficient cells displayed a high dependence on HSP90AB1 expression and diminishing HSP90 activity further using the HSP90 inhibitor Ganetespib resulted in increased therapeutic vulnerability in both colorectal and breast cancer cells in vitro. Accordingly, subcutaneously transplanted CRC cells deficient in USP22 expression displayed increased sensitivity towards Ganetespib treatment in vivo. Together, we discovered that HSP90AB1 is USP22-dependent and that cooperative targeting of USP22 and HSP90 may provide an effective approach to the treatment of colorectal and breast cancer.
Exploring the potential of BH3 mimetic therapy in squamous cell carcinoma of the head and neck
Authors: Carter Rachel J. , Milani Mateus , Butterworth Michael , Alotibi Ahoud , Harper Nicholas , Yedida Govindaraju , Greaves Georgia , Al-Zebeeby Aoula , Jorgensen Andrea L. , Schache Andrew G. , Risk Janet M. , Shaw Richard J. , Jones Terry M. , Sacco Joseph J. , Hurlstone Adam , Cohen Gerald M. , Varadarajan Shankar 
Published: December 2019

AbstractSquamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer worldwide, with overall survival of less than 50%. Current therapeutic strategies involving a combination of surgery, radiation, and/or chemotherapy are associated with debilitating side effects, highlighting the need for more specific and efficacious therapies. Inhibitors of BCL-2 family proteins (BH3 mimetics) are under investigation or in clinical practice for several hematological malignancies and show promise in solid tumors. In order to explore the therapeutic potential of BH3 mimetics in the treatment of SCCHN, we assessed the expression levels of BCL-2, BCL-XL, and MCL-1 via Western blots and immunohistochemistry, in cell lines, primary cells derived from SCCHN patients and in tissue microarrays containing tumor tissue from a cohort of 191 SCCHN patients. All preclinical models exhibited moderate to high levels of BCL-XL and MCL-1, with little or no BCL-2. Although expression levels of BCL-XL and MCL-1 did not correlate with patient outcome, a combination of BH3 mimetics to target these proteins resulted in decreased clonogenic potential and enhanced apoptosis in all preclinical models, including tumor tissue resected from patients, as well as a reduction of tumor volume in a zebrafish xenograft model of SCCHN. Our results show that SCCHN is dependent on both BCL-XL and MCL-1 for apoptosis evasion and combination therapy targeting both proteins may offer significant therapeutic benefits in this disease.
Association of N6-methyladenine DNA with plaque progression in atherosclerosis via myocardial infarction-associated transcripts
Authors: Wu Lianpin , Pei Yuqing , Zhu Yinhuan , Jiang Minghua , Wang Cheng , Cui Wei , Zhang Donghong 
Published: December 2019

AbstractModification of the novel N6-methyladenine (m6A) DNA implicates this epigenetic mark in human malignant disease, but its role in atherosclerosis (AS) is largely unknown. Here, we found that the leukocyte level of m6A but not 5mC DNA modification was decreased with increasing of carotid plaque size and thickness in 207 AS patients as compared with 142 sex- and age-matched controls. Serum low-density lipoprotein (LDL) and leukocyte m6A levels were associated with the progression of carotid plaque size and thickness. Both LDL level and plaque thickness were also independently and negatively related to m6A level. Reduced m6A level was further confirmed in leukocytes and endothelium in western diet-induced AS mice and in oxidized-LDL (ox-LDL)-treated human endothelium and monocyte cells. Decreased m6A level was closely related to the upregulation of AlkB homolog 1 (ALKBH1), the demethylase of m6A. Silencing of ALKBH1 or hypoxia-inducible factor 1α (HIF1α) could rescue the ox-LDL–increased level of MIAT, a hypoxia-response gene. Mechanically, ox-LDL induced HIF1α for transfer into the nucleus. Nuclear HIF1α bound to the ALKBH1-demethylated MIAT promoter and transcriptionally upregulated its expression. Therefore, elevated ALKBH1 level in endothelium and leukocytes reduced m6A level, which is a novel and sensitive biomarker for AS progression.
Reciprocal regulation of miR-1205 and E2F1 modulates progression of laryngeal squamous cell carcinoma
Authors: Li Pei , Lin Xi-Jun , Yang Yang , Yang An-Kui , Di Jin-Ming , Jiang Qi-Wei , Huang Jia-Rong , Yuan Meng-Ling , Xing Zi-Hao , Wei Meng-Ning , Li Yao , Yuan Xiao-Hui , Shi Zhi , Liu Hui , Ye Jin 
Published: December 2019

AbstractThe burgeoning functions of many microRNAs (miRs) have been well study in cancer. However, the level and function of miR-1205 in laryngeal squamous cell cancer remains unknown. In the current research, we validated that miR-1205 was notably downregulated in human laryngeal squamous cell carcinoma (LSCC) samples in comparison with tissues adjacent to LSCC, and correlated with T stage, lymph node metastasis, and clinical stage. Using Kaplan–Meier analysis indicates that high expression of miR-1205 has a favorable prognosis for patients with LSCC. Functional assays show that enforced miR-1205 expression attenuates the migration, growth, and invasion of LSCC cells. And E2F1 is verified to be a target of miR-1205, while E2F1 binds to miR-1205 promoter and transcriptionally inhibits miR-1205 expression. Overexpression of E2F1 reverses the inhibitory impacts of miR-1205 on LSCC cells in part. Importantly, E2F1 is abnormally increased in LSCC tissues, and its protein levels were inversely relevant to miR-1205 expression. High E2F1 protein level is in connection with clinical stage, T stage, lymph node metastasis, and poor prognosis. Consequently, reciprocal regulation of miR-1205 and E2F1 plays a crucial role in the progression of LSCC, suggesting a new miR-1205/E2F1-based clinical application for patients of LSCC.
Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K/AKT activation in B-cell lymphoid malignancies
Authors: Kapoor Isha , Li Yue , Sharma Arishya , Zhu Huayuan , Bodo Juraj , Xu Wei , Hsi Eric D. , Hill Brian T. , Almasan Alexandru 
Published: December 2019

AbstractChronic activation of the Bruton’s tyrosine kinase (BTK)-mediated B-cell receptor (BCR) signaling is a hallmark of many B-cell lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL). Ibrutinib, an FDA approved, orally administered BTK inhibitor, has demonstrated high response rates, however, complete responses are infrequent and acquired resistance to BTK inhibition can emerge. In this study, we generated ibrutinib-resistant (IB-R) cell lines by chronic exposure of CLL and activated B-cell (ABC)-DLBCL cells to ibrutinib in order to investigate the mechanism of acquired resistance to ibrutinib. IB-R cell lines demonstrated downregulation of FOXO3a and PTEN levels and activation of AKT, with their levels being low in the nuclei of resistant cells in comparison to the sensitive counterparts. Inhibition of PI3K and AKT using idelalisib and MK2206, respectively increased ibrutinib-induced apoptosis in IB-R cells by downregulation of pAKT473 and restoring FOXO3a levels, demonstrating the importance of these cell survival factors for ibrutinib-resistance. Notably, the exportin 1 inhibitor, selinexor synergized with ibrutinib in IB-R cells and restored nuclear abundance of FOXO3a and PTEN, suggesting that nuclear accumulation of FOXO3a and PTEN facilitates increase in ibrutinib-induced apoptosis in IB-R cells. These data demonstrate that reactivation of FOXO3a nuclear function enhances the efficacy of ibrutinib and overcomes acquired resistance to ibrutinib. Together, these findings reveal a novel mechanism that confers ibrutinib resistance via aberrant nuclear/cytoplasmic subcellular localization of FOXO3a and could be exploited by rational therapeutic combination regimens for effectively treating lymphoid malignancies.
eIF2α signaling regulates autophagy of osteoblasts and the development of osteoclasts in OVX mice
Authors: Li Jie , Li Xinle , Liu Daquan , Hamamura Kazunori , Wan Qiaoqiao , Na Sungsoo , Yokota Hiroki , Zhang Ping 
Published: December 2019

AbstractBone loss in postmenopausal osteoporosis is induced chiefly by an imbalance of bone-forming osteoblasts and bone-resorbing osteoclasts. Salubrinal is a synthetic compound that inhibits de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Phosphorylation of eIF2α alleviates endoplasmic reticulum (ER) stress, which may activate autophagy. We hypothesized that eIF2α signaling regulates bone homeostasis by promoting autophagy in osteoblasts and inhibiting osteoclast development. To test the hypothesis, we employed salubrinal to elevate the phosphorylation of eIF2α in an ovariectomized (OVX) mouse model and cell cultures. In the OVX model, salubrinal prevented abnormal expansion of rough ER and decreased the number of acidic vesiculars. It regulated ER stress-associated signaling molecules such as Bip, p-eIF2α, ATF4 and CHOP, and promoted autophagy of osteoblasts via regulation of eIF2α, Atg7, LC3, and p62. Salubrinal markedly alleviated OVX-induced symptoms such as reduction of bone mineral density and bone volume fraction. In primary bone-marrow-derived cells, salubrinal increased the differentiation of osteoblasts, and decreased the formation of osteoclasts by inhibiting nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). Live cell imaging and RNA interference demonstrated that suppression of osteoclastogenesis is in part mediated by Rac1 GTPase. Collectively, this study demonstrates that ER stress-autophagy axis plays an important role in OVX mice. Bone-forming osteoblasts are restored by maintaining phosphorylation of eIF2α, and bone-resorbing osteoclasts are regulated by inhibiting NFATc1 and Rac1 GTPase.
miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4
Authors: Du Feiya , Yu Ling , Wu Ying , Wang Shuqian , Yao Jia , Zheng Xiaoxiao , Xie Shangzhi , Zhang Shufeng , Lu Xuemei , Liu Yu , Chen Wei 
Published: December 2019

AbstractAcquired resistance to chemotherapy is a major obstacle in breast cancer (BC) treatment. Accumulated evidence has uncovered that microRNAs (miRNAs) are vital regulators of chemoresistance in cancer. Growing studies reveal that miR-137 acts as a suppressor in tumor progression. However, it remains obscure the role of miR-137 in modulating the sensitivity of BC cells to doxorubicin (DOX). In this study, we demonstrate that miR-137 exerts a significant effect on repressing the development of chemoresistance of BC cells in response to DOX via attenuating epithelial-mesenchymal transition (EMT) of tumor cells in vitro and in vivo. MiR-137 overexpression dramatically elevated the sensitivity of BC cells to DOX as well as impaired the DOX-promoted EMT of tumor cells. Mechanistically, miR-137 directly targeted dual-specificity phosphatase 4 (DUSP4) to impact on the EMT and chemoresistance of BC cells upon DOX treatment. Consistently, decreased DUSP4 efficiently enhanced the sensitivity of BC cells to DOX while overexpressed DUSP4 significantly diminished the beneficial effect of miR-137 on BC cells chemoresistance. Moreover, the increased miR-137 heightened the sensitivity of BC cells-derived tumors to DOX through targeting DUSP4 in vivo. Together, our results provide a novel insight into the DOX resistance of BC cells and miR-137 may serve as a new promising therapeutic target for overcoming chemoresistance in BC.