bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling the Recent Changes of Phytoplankton Blooms Dynamics in the Arctic Ocean
Authors: Manizza Manfredi , Carroll Dustin , Menemenlis Dimitris , Zhang Hong , Miller Charles E. 
Published: May 2023

AbstractIn recent decades, Arctic Ocean (AO) sea ice has experienced intense climate‐related modifications, which coincide with earlier melting in spring and delayed formation in the fall. In this study, we use the ECCO2‐Darwin ocean biogeochemistry model to gain a mechanistic understanding of how changes in sea‐ice seasonality impact the phenology of AO phytoplankton blooms. We use a 2006–2013 simulation to show that early sea‐ice melt in 2007 and 2012 triggers earlier phytoplankton blooms (∼1 month earlier compared to other years) and that the blooms dissipate earlier due to more rapid nutrient depletion in the surface AO. Our simulation also confirms that delayed formation of sea ice during fall triggers second fall blooms, in agreement with observations. These results suggest that in a warmer and changing climate, further changes to sea‐ice extent could drastically impact AO phytoplankton, with important consequences for Arctic marine ecosystems.
Depth Distribution of Chlorine at Gale Crater, Mars, as Derived From the DAN and APXS Experiments Onboard the Curiosity Rover
Authors: Litvak M. L. , Mitrofanov I. G. , Gellert R. , Djachkova M. V. , Lisov D. I. , Vasavada A. R. , Czarnecki S. 
Published: May 2023

AbstractThe subsurface chlorine depth distribution at Gale crater has been studied using measurements from the Alpha Particle X‐ray Spectrometer (APXS) and Dynamic Albedo of Neutrons (DAN) instruments onboard NASA's Curiosity Mars rover. These measurements have been acquired at or near ∼30 drill holes made by Curiosity along its 30 km drive. APXS measured a ∼15 micron surface layer of bedrock and shallow depth of ∼5 cm of drill tailings. DAN is sensitive to the bulk (∼50 cm depth) chlorine abundance and that of other neutron absorbing elements. Joint analysis of APXS and DAN data shows that the chlorine distribution at Gale crater consists of two components: surficial chlorine with concentrations >1 wt.%, possibly controlled by aeolian deposition of Cl‐rich dust and surface alteration, and subsurface chlorine with concentrations <1 wt.%, likely a result of groundwater activity in the past.
Modeling Bankfull Channel Geometry Based on Watershed and Precipitation Characteristics Using Dimensionless Parameters
Authors: Bastola Hridaya , Diplas Panayiotis 
Published: May 2023

AbstractRegression models have consistently identified discharge as a suitable variable for capturing the systematic trends in channel geometry. Using a discharge‐based relation, however, does not reflect the more fundamental dependence of channel geometry on basic watershed properties and precipitation characteristics. To explore relations between bankfull channel geometry and watershed properties, we consider two sets of dimensionless regression models: (a) with bankfull discharge as an independent variable, and (b) with bankfull discharge as a dependent variable. While bankfull discharge is used as an input variable in the first set of regression analyses, average annual precipitation has been used in the second set. Other watershed and channel variables considered include drainage area, median sediment grain size, and valley slope. A data set of 538 sandy and gravel channel reaches from UK, and various physiographic provinces of the USA is considered. By representing bankfull discharge, width, depth and watershed variables in the form of dimensionless parameters, we specify the relationship between channel morphology and watershed and precipitation characteristics using an approach that is applicable to sandy and gravel streams from a range of climatic and physiographic regions. The formulation presented here is an effort toward the development of models that will be capable of predicting bankfull channel dimensions and discharge under modified average annual precipitation due to change in climate.
Evaluating the efficacy and cardiotoxicity of EGFR-TKI AC0010 with a novel multifunctional biosensor
Authors: Jiang Deming , Wei Xinwei , Zhu Yuxuan , Qiu Yong , Liu Xin , Kong Liubing , Li Fengheng , Liu Jingwen , Zhuang Liujing , Wan Hao , Ying Kejing , Wang Ping 
Published: May 2023

AbstractNon-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide. Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have dramatically improved the life expectancy of patients with NSCLC, concerns about TKI-induced cardiotoxicities have increased. AC0010, a novel third-generation TKI, was developed to overcome drug resistance induced by EGFR-T790M mutation. However, the cardiotoxicity of AC0010 remains unclear. To evaluate the efficacy and cardiotoxicity of AC0010, we designed a novel multifunctional biosensor by integrating microelectrodes (MEs) and interdigital electrodes (IDEs) to comprehensively evaluate cell viability, electrophysiological activity, and morphological changes (beating of cardiomyocytes). The multifunctional biosensor can monitor AC0010-induced NSCLC inhibition and cardiotoxicity in a quantitative, label-free, noninvasive, and real-time manner. AC0010 was found to significantly inhibit NCI-H1975 (EGFR-L858R/T790M mutation), while weak inhibition was found for A549 (wild-type EGFR). Negligible inhibition was found in the viabilities of HFF-1 (normal fibroblasts) and cardiomyocytes. With the multifunctional biosensor, we found that 10 μM AC0010 significantly affected the extracellular field potential (EFP) and mechanical beating of cardiomyocytes. The amplitude of EFP continuously decreased after AC0010 treatment, while the interval decreased first and then increased. We analyzed the change in the systole time (ST) and diastole time (DT) within a beating interval and found that the DT and DT/beating interval rate decreased within 1 h after AC0010 treatment. This result probably indicated that the relaxation of cardiomyocytes was insufficient, which may further aggravate the dysfunction. Here, we found that AC0010 significantly inhibited EGFR-mutant NSCLC cells and impaired cardiomyocyte function at low concentrations (10 μM). This is the first study in which the risk of AC0010-induced cardiotoxicity was evaluated. In addition, novel multifunctional biosensors can comprehensively evaluate the antitumor efficacy and cardiotoxicity of drugs and candidate compounds.
Vimentin is required for tumor progression and metastasis in a mouse model of non–small cell lung cancer
Authors: Berr Alexandra L. , Wiese Kristin , dos Santos Gimena , Koch Clarissa M. , Anekalla Kishore R. , Kidd Martha , Davis Jennifer M. , Cheng Yuan , Hu Yuan-Shih , Ridge Karen M. 
Published: May 2023

AbstractVimentin is highly expressed in metastatic cancers, and its expression correlates with poor patient prognoses. However, no causal in vivo studies linking vimentin and non–small cell lung cancer (NSCLC) progression existed until now. We use three complementary in vivo models to show that vimentin is required for the progression of NSCLC. First, we crossed LSL-KrasG12D; Tp53fl/fl mice (KPV+/+) with vimentin knockout mice (KPV−/−) to demonstrate that KPV−/− mice have attenuated tumor growth and improved survival compared with KPV+/+ mice. Next, we therapeutically treated KPV+/+ mice with withaferin A (WFA), an agent that disrupts vimentin intermediate filaments (IFs). We show that WFA suppresses tumor growth and reduces tumor burden in the lung. Finally, luciferase-expressing KPV+/+, KPV−/−, or KPVY117L cells were implanted into the flanks of athymic mice to track cancer metastasis to the lung. In KPVY117L cells, vimentin forms oligomers called unit-length filaments but cannot assemble into mature vimentin IFs. KPV–/– and KPVY117L cells fail to metastasize, suggesting that cell-autonomous metastasis requires mature vimentin IFs. Integrative metabolomic and transcriptomic analysis reveals that KPV–/– cells upregulate genes associated with ferroptosis, an iron-dependent form of regulated cell death. KPV–/– cells have reduced glutathione peroxidase 4 (GPX4) levels, resulting in the accumulation of toxic lipid peroxides and increased ferroptosis. Together, our results demonstrate that vimentin is required for rapid tumor growth, metastasis, and protection from ferroptosis in NSCLC.
A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors
Authors: Zhang Chao , Guo Qiang , Chen Lifeng , Wu Zheming , Yan Xiao-Jian , Zou Chengyang , Zhang Qiuxue , Tan Jiahong , Fang Tian , Rao Qunxian , Li Yang , Shen Shizhen , Deng Min , Wang Liewei , Gao Huanyao , Yu Jia , Li Hu , Zhang Cheng , Nowsheen Somaira , Kloeber Jake , Zhao Fei , Yin Ping , Teng Chunbo , Lin Zhongqiu , Song Kun , Yao Shuzhong , Yao Liangqing , Wu Lingying , Zhang Yong , Cheng Xiaodong , Gao Qinglei , Yuan Jian , Lou Zhenkun , Zhang Jin-San 
Published: May 2023

AbstractPoly (ADP-ribose) polymerase (PARP) inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination (HR) deficiency. However, many patients without apparent HR defects also respond well to PARP inhibitors/cisplatin. The biomarker responsible for this mechanism remains unclear. Here, we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient patients. PARP inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage (ATM) signaling-induced pro-apoptotic ribosomal stress, which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA damage. Therefore, the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/cisplatin. The gene panel as an independent biomarker was validated by multiple published clinical datasets, as well as by an ovarian cancer organoids library we established. More importantly, its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS data. Furthermore, we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell lines. These drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired resistance. Together, our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy.
SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication
Authors: Pan Pan , Ge Weiwei , Lei Zhiwei , luo Wei , Liu Yuqing , Guan Zhanwen , Chen Lumiao , Yu Zhenyang , Shen Miaomiao , Hu Dingwen , Xiang Qi , Wang Wenbiao , Wan Pin , Tian Mingfu , Yu Yang , Luo Zhen , Chen Xulin , Xiao Heng , Zhang Qiwei , Liang Xujing , Chen Xin , Li Yongkui , Wu Jianguo 
Published: May 2023

AbstractViral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn’t. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.
Inhibition of extranodal NK/T-cell lymphoma by Chiauranib through an AIF-dependent pathway and its synergy with L-asparaginase
Authors: Gao Tianxiao , Huang Jieye , Yin Haofan , Huang Jiajia , Xie Jinye , Zhou Ti , Fan Wei , Yang Xia , Gao Guoquan , Li Zhiming 
Published: May 2023

AbstractExtranodal NK/T-cell lymphoma (NKTL) is a rare and aggressive form of extranodal lymphoma with a poor prognosis. Currently, there are very limited treatment options for patients with advanced-stage disease or those with relapsed/recurrent disease. Here we show that Chiauranib, an orally small molecule inhibitor of select serine-threonine kinases (aurora B, VEGFRs, PDGFR, CSF1R, c-Kit), inhibited NKTL cell proliferation, induced cell cycle arrest, as well as suppressed the microvessel density in vitro and in vivo similar as in other types of cancer cells. Surprisingly, Chiauranib unfolded a new effect to induce apoptosis of NKTL cells by triggering AIF-dependent apoptosis other than the traditional cyt-c/caspase mitochondrial apoptosis pathway. The knockdown of AIF in vitro and in vivo dramatically blocked the efficacy of Chiauranib on NKTL. Mechanistically, the release of AIF from mitochondria is due to the upregulation of VDAC1 by the AKT-GSK3β pathway and activation of calcium-dependent m-calpain, which promotes the cleavage of VDAC1 and therefore permits the release of AIF. Notably, the low expression of Bax in both NKTL cells and patient tissues restrained the cyt-c release. It resulted in the inhibition of cyt-c/caspase mitochondrial pathway, suggesting that drugs targeting this traditional pathway may not be effective in NKTL. Furthermore, we found that L-asparaginase triggered CD95 (Fas/Apo-1)-caspase 8-caspase 3 apoptotic pathway in NKTL cells, and combination of Chiauranib and L-asparaginase exhibited a synergistic effect, suggesting a feasibility to combine these two drugs for effective treatment of NKTL. This study demonstrates Chiauranib’s positive efficacy toward NKTL through the activation of the AIF-dependent apoptosis pathway for the first time. The novel and multi-targets of Chiauranib and the synergistic effect with L-asparaginase may provide a promising therapy for NKTL patients.
Serum amyloid protein A in inflammatory bowel disease: from bench to bedside
Authors: Chen Rirong , Chen Qia , Zheng Jieqi , Zeng Zhirong , Chen Minhu , Li Li , Zhang Shenghong 
Published: May 2023

AbstractInflammatory bowel diseases (IBD) is featured by gastrointestinal inflammation and a disease course with alternating recurrence and remission. The global burden caused by IBD has significantly boosted in recent years, necessitating treatment optimization. Serum amyloid A (SAA) is a class of 104 amino acid conservative acute-phase proteins, which is essential in immune-mediated inflammatory processes, like IBD. The SAA monomeric structure is composed of four α-helical regions and a C-terminal amorphous tail. Its disordered structure enables multiple bindings to different ligands and permits multiple functions. It has been proven that SAA has dual roles in the inflammatory process. SAA stimulates the pro-inflammatory cytokine expression and promotes the pathogenic differentiation of TH17 cells. In addition, SAA can remove toxic lipids produced during inflammatory responses and membrane debris from dead cells, redirect HDL, and recycle cholesterol for tissue repair. In IBD, SAA acts on gut epithelium barriers, induces T-cell differentiation, and promotes phagocytosis of Gram-negative bacteria. Owing to the tight connection between SAA and IBD, several clinical studies have taken SAA for a biomarker for diagnosis, assessing disease activity, and predicting prognosis in IBD. Furthermore, 5-MER peptide, a drug specifically targeting SAA, has shown anti-inflammatory effects in some SAA-dependent animal models, providing novel insights into the therapeutic targets of IBD.
Soft, miniaturized, wireless olfactory interface for virtual reality
Authors: Liu Yiming , Yiu Chun Ki , Zhao Zhao , Park Wooyoung , Shi Rui , Huang Xingcan , Zeng Yuyang , Wang Kuan , Wong Tsz Hung , Jia Shengxin , Zhou Jingkun , Gao Zhan , Zhao Ling , Yao Kuanming , Li Jian , Sha Chuanlu , Gao Yuyu , Zhao Guangyao , Huang Ya , Li Dengfeng , Guo Qinglei , Li Yuhang , Yu Xinge 
Published: May 2023

AbstractRecent advances in virtual reality (VR) technologies accelerate the creation of a flawless 3D virtual world to provide frontier social platform for human. Equally important to traditional visual, auditory and tactile sensations, olfaction exerts both physiological and psychological influences on humans. Here, we report a concept of skin-interfaced olfactory feedback systems with wirelessly, programmable capabilities based on arrays of flexible and miniaturized odor generators (OGs) for olfactory VR applications. By optimizing the materials selection, design layout, and power management, the OGs exhibit outstanding device performance in various aspects, from response rate, to odor concentration control, to long-term continuous operation, to high mechanical/electrical stability and to low power consumption. Representative demonstrations in 4D movie watching, smell message delivery, medical treatment, human emotion control and VR/AR based online teaching prove the great potential of the soft olfaction interface in various practical applications, including entertainment, education, human machine interfaces and so on.
Molecular mechanisms of tubulogenesis revealed in the sea star hydro-vascular organ
Authors: Perillo Margherita , Swartz S. Zachary , Pieplow Cosmo , Wessel Gary M. 
Published: May 2023

AbstractA fundamental goal in the organogenesis field is to understand how cells organize into tubular shapes. Toward this aim, we have established the hydro-vascular organ in the sea star Patiria miniata as a model for tubulogenesis. In this animal, bilateral tubes grow out from the tip of the developing gut, and precisely extend to specific sites in the larva. This growth involves cell migration coupled with mitosis in distinct zones. Cell proliferation requires FGF signaling, whereas the three-dimensional orientation of the organ depends on Wnt signaling. Specification and maintenance of tube cell fate requires Delta/Notch signaling. Moreover, we identify target genes of the FGF pathway that contribute to tube morphology, revealing molecular mechanisms for tube outgrowth. Finally, we report that FGF activates the Six1/2 transcription factor, which serves as an evolutionarily ancient regulator of branching morphogenesis. This study uncovers distinct mechanisms of tubulogenesis in vivo and we propose that cellular dynamics in the sea star hydro-vascular organ represents a key comparison for understanding the evolution of vertebrate organs.
Skin basal cell carcinomas assemble a pro-tumorigenic spatially organized and self-propagating Trem2+ myeloid niche
Authors: Haensel Daniel , Daniel Bence , Gaddam Sadhana , Pan Cory , Fabo Tania , Bjelajac Jeremy , Jussila Anna R. , Gonzalez Fernanda , Li Nancy Yanzhe , Chen Yun , Hou JinChao , Patel Tiffany , Aasi Sumaira , Satpathy Ansuman T. , Oro Anthony E. 
Published: May 2023

AbstractCancer immunotherapies have revolutionized treatment but have shown limited success as single-agent therapies highlighting the need to understand the origin, assembly, and dynamics of heterogeneous tumor immune niches. Here, we use single-cell and imaging-based spatial analysis to elucidate three microenvironmental neighborhoods surrounding the heterogeneous basal cell carcinoma tumor epithelia. Within the highly proliferative neighborhood, we find that TREM2+ skin cancer-associated macrophages (SCAMs) support the proliferation of a distinct tumor epithelial population through an immunosuppression-independent manner via oncostatin-M/JAK-STAT3 signaling. SCAMs represent a unique tumor-specific TREM2+ population defined by VCAM1 surface expression that is not found in normal homeostatic skin or during wound healing. Furthermore, SCAMs actively proliferate and self-propagate through multiple serial tumor passages, indicating long-term potential. The tumor rapidly drives SCAM differentiation, with intratumoral injections sufficient to instruct naive bone marrow-derived monocytes to polarize within days. This work provides mechanistic insights into direct tumor-immune niche dynamics independent of immunosuppression, providing the basis for potential combination tumor therapies.
Zinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface
Authors: Amagai Yuta , Yamada Momo , Kowada Toshiyuki , Watanabe Tomomi , Du Yuyin , Liu Rong , Naramoto Satoshi , Watanabe Satoshi , Kyozuka Junko , Anelli Tiziana , Tempio Tiziana , Sitia Roberto , Mizukami Shin , Inaba Kenji 
Published: May 2023

AbstractMany secretory enzymes acquire essential zinc ions (Zn2+) in the Golgi complex. ERp44, a chaperone operating in the early secretory pathway, also binds Zn2+ to regulate its client binding and release for the control of protein traffic and homeostasis. Notably, three membrane transporter complexes, ZnT4, ZnT5/ZnT6 and ZnT7, import Zn2+ into the Golgi lumen in exchange with protons. To identify their specific roles, we here perform quantitative Zn2+ imaging using super-resolution microscopy and Zn2+-probes targeted in specific Golgi subregions. Systematic ZnT-knockdowns reveal that ZnT4, ZnT5/ZnT6 and ZnT7 regulate labile Zn2+ concentration at the distal, medial, and proximal Golgi, respectively, consistent with their localization. Time-course imaging of cells undergoing synchronized secretory protein traffic and functional assays demonstrates that ZnT-mediated Zn2+ fluxes tune the localization, trafficking, and client-retrieval activity of ERp44. Altogether, this study provides deep mechanistic insights into how ZnTs control Zn2+ homeostasis and ERp44-mediated proteostasis along the early secretory pathway.
Resistance to anti-HER2 therapy associated with the TSC2 nonsynonymous variant c.4349 C > G (p.Pro1450Arg) is reversed by CDK4/6 inhibitor in HER2-positive breast cancer
Authors: Yang Ziyan , Feng Jianguo , Jing Ji , Huang Yuan , Ye Wei-Wu , Lei Lei , Wang Xiao-Jia , Cao Wen-Ming 
Published: May 2023

AbstractHER2-positive breast cancer patients carrying the germline TSC2 nonsynonymous variant c.4349 C > G (p.Pro1450Arg) are resistant to anti-HER2 therapy. Multi-predictor in silico analysis reveals that this variant is deleterious. We explore the potential mechanism of this TSC2 variant and investigate methods for overcoming anti-HER2 resistance. TSC2 c.4349 C > G reverses the inhibitory effect on mTOR and downstream signaling by increasing TSC2 phosphorylation at Thr1462 and confers significant lapatinib resistance in vitro and in vivo. The combination of lapatinib and the CDK4/6 inhibitor palbociclib inhibits cyclin D1/CDK4/Rb alternative pathway and TSC2 phosphorylation, thereby partially attenuating mTOR activity and inducing TSC2-mutant cell blockage at G1/G0. In in vitro and xenograft models, palbociclib+lapatinib shows higher anti-tumor activity than monotherapy and overcomes the resistance of the TSC2 c.4349 C > G-related variant to anti-HER2 therapy. We reveal a new mechanism of resistance to anti-HER2 therapy and provide a strategy to increase the efficiency of anti-HER2 therapy in HER2-positive breast cancer.