bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climate Change in China Affects Runoff and Terrestrial Ecosystem Water Retention More Than Changes in Leaf Area Index and Land Use/Cover Over the Period 1982–2015
Authors: Zhai Ran , Tao Fulu 
Published: March 2021

AbstractClimate, land use/cover, and leaf area index (LAI) have changed notably in China since 1980, and these have had major impacts on river runoff and the terrestrial ecosystem water retention (TEWR) service in China. However, the mechanisms underlying the spatiotemporal changes of runoff and TEWR are not understood well. Here, meteorological, LAI, and land use/cover data were applied in a hydrological model (variable infiltration capacity) to quantify their contributions to runoff and TEWR changes during the 1980s, the 1990s, the 2000s, and 1982–2015, respectively. The results show that climate change, particularly precipitation change, was the dominant factor controlling runoff and TEWR changes. Between 1982 and 2015, climate change increased the runoff in large areas in northwestern and southwestern China and the Hai River (HR) basin and improved the TEWR in large areas in northwestern and northeastern China and the Huai River (HuR) basin. However, the magnitudes and signs of the climate change impact varied in different regions and time periods. The LAI increased extensively, which led to decreased runoff and increased TEWR in most of China from 1982 to 2015, especially in the Yellow River basin, HuR basin, and HR basin. The impacts of land use/cover change on runoff and TEWR were in general less than those of climate and LAI changes, nevertheless, they were important in some local areas. This study improves the understanding of the spatiotemporal patterns and the underlying mechanisms of runoff and TEWR changes across China between 1982 and 2015.
A Quarter Century ofWindSpacecraft Discoveries
Authors: Wilson Lynn B. , Brosius Alexandra L. , Gopalswamy Natchimuthuk , Nieves‐Chinchilla Teresa , Szabo Adam , Hurley Kevin , Phan Tai , Kasper Justin C. , Lugaz Noé , Richardson Ian G. , Chen Christopher H. K. , Verscharen Daniel , Wicks Robert T. , TenBarge Jason M. 
Published: March 2021

AbstractTheWindspacecraft, launched on November 1, 1994, is a critical element in NASA’s Heliophysics System Observatory (HSO)—a fleet of spacecraft created to understand the dynamics of the Sun‐Earth system. The combination of its longevity (>25 years in service), its diverse complement of instrumentation, and high resolution and accurate measurements has led to it becoming the “standard candle” of solar wind measurements.Windhas over 55 selectable public data products with over ∼1,100 total data variables (including OMNI data products) on SPDF/CDAWeb alone. These data have led to paradigm shifting results in studies of statistical solar wind trends, magnetic reconnection, large‐scale solar wind structures, kinetic physics, electromagnetic turbulence, the Van Allen radiation belts, coronal mass ejection topology, interplanetary and interstellar dust, the lunar wake, solar radio bursts, solar energetic particles, and extreme astrophysical phenomena such as gamma‐ray bursts. This review introduces the mission and instrument suites then discusses examples of the contributions byWindto these scientific topics that emphasize its importance to both the fields of heliophysics and astrophysics.
Determination of Auroral Electrodynamic Parameters From AMPERE Field‐Aligned Current Measurements
Authors: Robinson R. M. , Zanetti Larry , Anderson Brian , Vines Sarah , Gjerloev Jesper 
Published: March 2021

AbstractWe calculate high latitude electrodynamic parameters using global maps of field‐aligned currents from the Active Magnetosphere and Planetary Response Experiment (AMPERE). The model is based on previous studies that relate field‐aligned currents to auroral Pedersen and Hall conductances measured by incoherent scatter radar. The field‐aligned currents and conductances are used to solve for the electric potential at high latitudes from which electric fields are computed. The electric fields are then used with the conductances to calculate horizontal ionospheric currents. We validate the results by simulating the SuperMAG magnetic indices for 30 geomagnetically active days. The correlation coefficients between derived and actual magnetic indices were 0.68, 0.76, and 0.84 for the SMU, SML, and SME indices, respectively. We show examples of times when the simulations differ markedly from the measured indices and attribute them to either small‐scale, substorm‐related current structures or the effects of neutral winds. Overall, the performance of the model demonstrates that with few exceptions, auroral electrodynamic parameters can be accurately deduced from the global field‐aligned current distribution provided by AMPERE.
Cancer metastasis as a non-healing wound
Authors: Deyell Matthew , Garris Christopher S. , Laughney Ashley M. 
Published: March 2021

AbstractMost cancer deaths are caused by metastasis: recurrence of disease by disseminated tumour cells at sites distant from the primary tumour. Large numbers of disseminated tumour cells are released from the primary tumour, even during the early stages of tumour growth. However, only a minority survive as potential seeds for future metastatic outgrowths. These cells must adapt to a relatively inhospitable microenvironment, evade immune surveillance and progress from the micro- to macro-metastatic stage to generate a secondary tumour. A pervasive driver of this transition is chronic inflammatory signalling emanating from tumour cells themselves. These signals can promote migration and engagement of stem and progenitor cell function, events that are also central to a wound healing response. In this review, we revisit the concept of cancer as a non-healing wound, first introduced by Virchow in the 19th century, with a new tumour cell-intrinsic perspective on inflammation and focus on metastasis. Cellular responses to inflammation in both wound healing and metastasis are tightly regulated by crosstalk with the surrounding microenvironment. Targeting or restoring canonical responses to inflammation could represent a novel strategy to prevent the lethal spread of cancer.
USP42 drives nuclear speckle mRNA splicing via directing dynamic phase separation to promote tumorigenesis
Authors: Liu Shuyan , Wang Taishu , Shi Yulin , Bai Lu , Wang Shanshan , Guo Dong , Zhang Yang , Qi Yangfan , Chen Chaoqun , Zhang Jinrui , Zhang Yingqiu , Liu Quentin , Yang Qingkai , Wang Yang , Liu Han 
Published: March 2021

AbstractLiquid–liquid phase separation is considered a generic approach to organize membrane-less compartments, enabling the dynamic regulation of phase-separated assemblies to be investigated and pivotal roles of protein posttranslational modifications to be demonstrated. By surveying the subcellular localizations of human deubiquitylases, USP42 was identified to form nuclear punctate structures that are associated with phase separation properties. Bioinformatic analysis demonstrated that the USP42 C-terminal sequence was intrinsically disordered, which was further experimentally confirmed to confer phase separation features. USP42 is distributed to SC35-positive nuclear speckles in a positively charged C-terminal residue- and enzymatic activity-dependent manner. Notably, USP42 directs the integration of the spliceosome component PLRG1 into nuclear speckles, and its depletion interferes with the conformation of SC35 foci. Functionally, USP42 downregulation deregulates multiple mRNA splicing events and leads to deterred cancer cell growth, which is consistent with the impact of PLRG1 repression. Finally, USP42 expression is strongly correlated with that of PLRG1 in non-small-cell lung cancer samples and predicts adverse prognosis in overall survival. As a deubiquitylase capable of dynamically guiding nuclear speckle phase separation and mRNA splicing, USP42 inhibition presents a novel anticancer strategy by targeting phase separation.
Targeting the autophagy promoted antitumor effect of T-DM1 on HER2-positive gastric cancer
Authors: Zhang Jinghui , Fan Jiajun , Zeng Xian , Nie Mingming , Chen Wei , Wang Yichen , Luan Jingyun , Zhu Zeguo , Chang Xusheng , Ju Dianwen , Feng Li , Yin Kai 
Published: March 2021

AbstractTrastuzumab emtansine (T-DM1), an antibody-drug conjugate consisted of the HER2-targeted monoclonal antibody trastuzumab and the tubulin inhibitor emtansine, has shown potent therapeutic value in HER2-positive breast cancer (BC). However, a clinical trial indicated that T-DM1 exerts a limited effect on HER2-positive gastric cancer (GC), but the underlying mechanism is inconclusive. Our research attempted to reveal the probable mechanism and role of autophagy in T-DM1-treated HER2-positive GC. In this study, our results showed that T-DM1 induced apoptosis and exhibited potent therapeutic efficacy in HER2-positive GC cells. In addition, autophagosomes were observed by transmission electron microscopy. Autophagy was markedly activated and exhibited the three characterized gradations of autophagic flux, consisting of the formation of autophagosomes, the fusion of autophagosomes with lysosomes, and the deterioration of autophagosomes in autolysosomes. More importantly, autophagic inhibition by the suppressors 3-methyladenine (3-MA) and LY294002 significantly potentiated cytotoxicity and apoptosis in HER2-positive GC cells in vitro, while the combined use of LY294002 and T-DM1 elicited potent anti-GC efficacy in vivo. In mechanistic experiments, immunoblot analysis indicated the downregulated levels of Akt, mTOR, and P70S6K and confocal microscopy analysis clearly showed that autophagic inhibition promoted the fusion of T-DM1 molecules with lysosomes in GC cells. In conclusion, our research demonstrated that T-DM1 induced apoptosis as well as cytoprotective autophagy, and autophagic inhibition could potentiate the antitumor effect of T-DM1 on HER2-positive GC. Furthermore, autophagic inhibition might increase the fusion of T-DM1 with lysosomes, which might accelerate the release of the cytotoxic molecule emtansine from the T-DM1 conjugate. These findings highlight a promising therapeutic strategy that combines T-DM1 with an autophagy inhibitor to treat HER-positive GC more efficiently.
RNA decay in processing bodies is indispensable for adipogenesis
Authors: Maeda Ryotaro , Kami Daisuke , Shikuma Akira , Suzuki Yosuke , Taya Toshihiko , Matoba Satoaki , Gojo Satoshi 
Published: March 2021

AbstractThe RNA decay pathway plays key regulatory roles in cell identities and differentiation processes. Although adipogenesis is transcriptionally and epigenetically regulated and has been thoroughly investigated, how RNA metabolism that contributes to the stability of phenotype-shaping transcriptomes participates in differentiation remains elusive. In this study, we investigated Ddx6, an essential component of processing bodies (PBs) that executes RNA decay and translational repression in the cytoplasm and participates in the cellular transition of reprogramming. Upon adipogenic induction, Ddx6 dynamically accumulated to form PBs with a binding partner, 4E-T, at the early phase prior to emergence of intracellular lipid droplets. In contrast, preadipocytes with Ddx6 knockout (KO) or 4E-T knockdown (KD) failed to generate PBs, resulting in significant suppression of adipogenesis. Transcription factors related to preadipocytes and negative regulators of adipogenesis that were not expressed under adipogenic stimulation were maintained in Ddx6-KO and 4E-T-KD preadipocytes under adipogenic induction. Elimination of Dlk1, a major negative regulator of adipogenesis, in 3T3L1 Ddx6-KO cells did not restore adipogenic differentiation capacity to any extent. Similar to murine cells, human primary mesenchymal stem cells, which can differentiate into adipocytes upon stimulation with adipogenic cocktails, required DDX6 to maturate into adipocytes. Therefore, RNA decay of the entire parental transcriptome, rather than removal of a strong negative regulator, could be indispensable for adipogenesis.
The emerging role of ferroptosis in intestinal disease
Authors: Xu Shu , He Yao , Lin Lihui , Chen Peng , Chen Minhu , Zhang Shenghong 
Published: March 2021

AbstractFerroptosis is a newly recognised type of regulated cell death (RCD) characterised by iron-dependent accumulation of lipid peroxidation. It is significantly distinct from other RCDs at the morphological, biochemical, and genetic levels. Recent reports have implicated ferroptosis in multiple diseases, including neurological disorders, kidney injury, liver diseases, and cancer. Ferroptotic cell death has also been associated with dysfunction of the intestinal epithelium, which contributes to several intestinal diseases. Research on ferroptosis may provide a new understanding of intestinal disease pathogenesis that benefits clinical treatment. In this review, we provide an overview of ferroptosis and its underlying mechanisms, then describe its emerging role in intestinal diseases, including intestinal ischaemia/reperfusion (I/R) injury, inflammatory bowel disease (IBD), and colorectal cancer (CRC).
Splicing reprogramming of TRAIL/DISC-components sensitizes lung cancer cells to TRAIL-mediated apoptosis
Authors: Voss Oliver H. , Arango Daniel , Tossey Justin C. , Villalona Calero Miguel A. , Doseff Andrea I. 
Published: March 2021

AbstractTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selective killing of cancer cells underlines its anticancer potential. However, poor tolerability and resistance underscores the need to identify cancer-selective TRAIL-sensitizing agents. Apigenin, a dietary flavonoid, sensitizes lung cancer cell lines to TRAIL. It remains unknown, however, whether apigenin sensitizes primary lung cancer cells to TRAIL and its underlying mechanisms. Here we show that apigenin reprograms alternative splicing of key TRAIL/death-inducing-signaling-complex (DISC) components: TRAIL Death Receptor 5 (DR5) and cellular-FLICE-inhibitory-protein (c-FLIP) by interacting with the RNA-binding proteins hnRNPA2 and MSI2, resulting in increased DR5 and decreased c-FLIPS protein levels, enhancing TRAIL-induced apoptosis of primary lung cancer cells. In addition, apigenin directly bound heat shock protein 70 (Hsp70), promoting TRAIL/DISC assembly and triggering apoptosis. Our findings reveal that apigenin directs alternative splicing and inhibits Hsp70 enhancing TRAIL anticancer activity. These findings underscore impactful synergies between diet and cancer treatments opening new avenues for improved cancer treatments.
hnRNPK-regulated LINC00263 promotes malignant phenotypes through miR-147a/CAPN2
Authors: Lee Woo Joo , Shin Chang Hoon , Ji Haein , Jeong Seong Dong , Park Mi-So , Won Hong-Hee , Pandey Poonam R. , Tsitsipatis Dimitrios , Gorospe Myriam , Kim Hyeon Ho 
Published: March 2021

AbstractMalignant characteristics of cancers, represented by rapid cell proliferation and high metastatic potential, are a major cause of high cancer-related mortality. As a multifunctional RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK) is closely associated with cancer progression in various types of cancers. In this study, we sought to identify hnRNPK-regulated long intergenic non-coding RNAs (lincRNAs) that play a critical role in the regulation of cancer malignancy. We found that hnRNPK controlled malignant phenotypes including invasiveness, proliferation, and clonogenicity. RNA sequencing and functional studies revealed that LINC00263, a novel target of hnRNPK, is involved in the oncogenic functions of hnRNPK. Knockdown of LINC00263 mitigated the malignant capabilities. Conversely, increased malignant phenotypes were observed in LINC00263-overexpressing cells. Since LINC00263 was mainly localized in the cytosol and highly enriched in Argonaute 2-immunoprecipitation (Ago2-IP), we hypothesized that LINC00263 acts as a competitive endogenous RNA (ceRNA), and thus sought to identify LINC00263-associated microRNAs. Using small RNA sequencing followed by antisense oligonucleotide pull-down, miR-147a was selected for further study. We found that miR-147a negatively regulates LINC00263 via direct interaction, thus suppressing malignant capabilities. Moreover, knockdown of hnRNPK and LINC00263 upregulated miR-147a, indicating that LINC00263 serves as a ceRNA for miR-147a. By analyzing RNA sequencing data and miRNA target prediction, calpain 2 (CAPN2) was identified as a putative target of miR-147a. Ago2-IP and luciferase reporter assay revealed that miR-147a suppressed CAPN2 expression by directly binding to the 3′UTR of CAPN2 mRNA. In addition, we found that the weakened malignant capabilities following knockdown of hnRNPK or LINC00263 were restored by miR-147a inhibition or CAPN2 overexpression. Furthermore, our findings were validated in various other types of cancer cells including lung cancer, colorectal cancer, neuroblastoma, and melanoma. Collectively, we demonstrate that hnRNPK-regulated LINC00263 plays an important role in cancer malignancy by acting as a miR-147a decoy and thus upregulating CAPN2.
Inhibition of eIF5A hypusination reprogrammes metabolism and glucose handling in mouse kidney
Authors: Cougnon Marc , Carcy Romain , Melis Nicolas , Rubera Isabelle , Duranton Christophe , Dumas Karine , Tanti Jean-François , Pons Catherine , Soubeiran Nicolas , Shkreli Marina , Hauet Thierry , Pellerin Luc , Giraud Sébastien , Blondeau Nicolas , Tauc Michel , Pisani Didier F. 
Published: March 2021

AbstractInhibition of the eukaryotic initiation factor 5A activation by the spermidine analogue GC7 has been shown to protect proximal cells and whole kidneys against an acute episode of ischaemia. The highlighted mechanism involves a metabolic switch from oxidative phosphorylation toward glycolysis allowing cells to be transiently independent of oxygen supply. Here we show that GC7 decreases protein expression of the renal GLUT1 glucose transporter leading to a decrease in transcellular glucose flux. At the same time, GC7 modifies the native energy source of the proximal cells from glutamine toward glucose use. Thus, GC7 acutely and reversibly reprogrammes function and metabolism of kidney cells to make glucose its single substrate, and thus allowing cells to be oxygen independent through anaerobic glycolysis. The physiological consequences are an increase in the renal excretion of glucose and lactate reflecting a decrease in glucose reabsorption and an increased glycolysis. Such a reversible reprogramming of glucose handling and oxygen dependence of kidney cells by GC7 represents a pharmacological opportunity in ischaemic as well as hyperglycaemia-associated pathologies from renal origin.
Splicing factor USP39 promotes ovarian cancer malignancy through maintaining efficient splicing of oncogenic HMGA2
Authors: Wang Shourong , Wang Zixiang , Li Jieyin , Qin Junchao , Song Jianping , Li Yingwei , Zhao Ling , Zhang Xiyu , Guo Haiyang , Shao Changshun , Kong Beihua , Liu Zhaojian 
Published: March 2021

AbstractAberrant expression of splicing factors was found to promote tumorigenesis and the development of human malignant tumors. Nevertheless, the underlying mechanisms and functional relevance remain elusive. We here show that USP39, a component of the spliceosome, is frequently overexpressed in high-grade serous ovarian carcinoma (HGSOC) and that an elevated level of USP39 is associated with a poor prognosis. USP39 promotes proliferation/invasion in vitro and tumor growth in vivo. Importantly, USP39 was transcriptionally activated by the oncogene protein c-MYC in ovarian cancer cells. We further demonstrated that USP39 colocalizes with spliceosome components in nuclear speckles. Transcriptomic analysis revealed that USP39 deletion led to globally impaired splicing that is characterized by skipped exons and overrepresentation of introns and intergenic regions. Furthermore, RNA immunoprecipitation sequencing showed that USP39 preferentially binds to exon-intron regions near 5′ and 3′ splicing sites. In particular, USP39 facilitates efficient splicing of HMGA2 and thereby increases the malignancy of ovarian cancer cells. Taken together, our results indicate that USP39 functions as an oncogenic splicing factor in ovarian cancer and represents a potential target for ovarian cancer therapy.
Islet neogenesis associated protein (INGAP) protects pancreatic β cells from IL-1β and IFNγ-induced apoptosis
Authors: Nano Eni , Petropavlovskaia Maria , Rosenberg Lawrence 
Published: March 2021

AbstractThe goal of this study was to determine whether recombinant Islet NeoGenesis Associated Protein (rINGAP) and its active core, a pentadecapeptide INGAP104–118 (Ingap-p), protect β cells against cytokine-induced death. INGAP has been shown to induce islet neogenesis in diabetic animals, to stimulate β-cell proliferation and differentiation, and to improve islet survival and function. Importantly, Ingap-p has shown promising results in clinical trials for diabetes (phase I/II). However, the full potential of INGAP and its mechanisms of action remain poorly understood. Using rat insulinoma cells RINm5F and INS-1 treated with interleukin-1β (IL-1β) and interferon‐gamma (IFN‐γ), we demonstrate here that both rINGAP and Ingap-p inhibit apoptosis, Caspase-3 activation, inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, and explore the related signaling pathways. As expected, IL-1β induced nuclear factor kappa B (NF-κB), p38, and JNK signaling, whereas interferon‐gamma (IFN‐γ) activated the JAK2/STAT1 pathway and potentiated the IL-1β effects. Both rINGAP and Ingap-p decreased phosphorylation of IKKα/β, IkBα, and p65, although p65 nuclear translocation was not inhibited. rINGAP, used for further analysis, also inhibited STAT3, p38, and JNK activation. Interestingly, all inhibitory effects of rINGAP were observed for the cytokine cocktail, not IL-1β alone, and were roughly equal to reversing the potentiating effects of INFγ. Furthermore, rINGAP had no effect on IL-1β/NF-κB-induced gene expression (e.g., Ccl2, Sod2) but downregulated several IFNγ-stimulated (Irf1, Socs1, Socs3) or IFNγ-potentiated (Nos2) genes. This, however, was observed again only for the cytokine cocktail, not IFNγ alone, and rINGAP did not inhibit the IFNγ-induced JAK2/STAT1 activation. Together, these intriguing results suggest that INGAP does not target either IL-1β or IFNγ individually but rather inhibits the signaling crosstalk between the two, the exact mechanism of which remains to be investigated. In summary, our study characterizes the anti-inflammatory effects of INGAP, both protein and peptide, and suggests a new therapeutic utility for INGAP in the treatment of diabetes.
Control of quantum electrodynamical processes by shaping electron wavepackets
Authors: Wong Liang Jie , Rivera Nicholas , Murdia Chitraang , Christensen Thomas , Joannopoulos John D. , Soljačić Marin , Kaminer Ido 
Published: March 2021

AbstractFundamental quantum electrodynamical (QED) processes, such as spontaneous emission and electron-photon scattering, encompass phenomena that underlie much of modern science and technology. Conventionally, calculations in QED and other field theories treat incoming particles as single-momentum states, omitting the possibility that coherent superposition states, i.e., shaped wavepackets, can alter fundamental scattering processes. Here, we show that free electron waveshaping can be used to design interferences between two or more pathways in a QED process, enabling precise control over the rate of that process. As an example, we show that free electron waveshaping modifies both spatial and spectral characteristics of bremsstrahlung emission, leading for instance to enhancements in directionality and monochromaticity. The ability to tailor general QED processes opens up additional avenues of control in phenomena ranging from optical excitation (e.g., plasmon and phonon emission) in electron microscopy to free electron lasing in the quantum regime.