bluuebunny/crossref_metadata_2025_split huggingface dataset:
The interplay of transcriptional coregulator NUPR1 with SREBP1 promotes hepatocellular carcinoma progression via upregulation of lipogenesis
Authors: Wang Yongjia , Zhang Yuqin , Wang Zixuan , Yu Lu , Chen Keli , Xie Yuwen , Liu Yang , Liang Weijie , Zheng Yilin , Zhan Yizhi , Ding Yi 
Published: October 2022

AbstractNuclear protein 1 (NUPR1) is a transcriptional coregulator that has been implicated in the development of various cancer types. In addition, de novo fatty acid synthesis plays a pivotal role in hepatocellular carcinoma (HCC) development. However, little is currently known on the role of NUPR1 in hepatocellular carcinoma. In this study, bioinformatics analysis was conducted to analyze the expression level, prognosis value and enriched pathways of NUPR1 in Liver Hepatocellular Carcinoma (LIHC). We found that NUPR1 was significantly upregulated in human hepatocellular carcinoma cells compared with normal hepatocytes from LIHC patients in TCGA cohorts and our patients. Kaplan–Meier analysis and COX proportional hazard progression model showed that high expression of NUPR1 was correlated with a poor prognosis of LIHC patients. CCK-8, EdU and colony formation assays were performed to explore the effect of NUPR1 on the proliferation of HCC cells, then wound healing and transwell migration assays were performed to evaluate the effects of NUPR1 on cell migration. Furthermore, subcutaneous xenograft models were established to study tumor growth. Results showed that NUPR1 overexpression correlated with a highly proliferative and aggressive phenotype. In addition, NUPR1 knockdown significantly inhibited hepatocellular carcinoma cell proliferation and migration in vitro and hindered tumorigenesis in vivo. Mechanistically, endogenous NUPR1 could interact with sterol regulatory element binding protein 1 (SREBP1) and upregulated lipogenic gene expression of fatty acid synthase (FASN), resulting in the accumulation of lipid content. Moreover, pharmacological or genetic blockade of the NUPR1-SREBP1/FASN pathway enhanced anticancer activity in vitro and in vivo. Overall, we identified a novel function of NUPR1 in regulating hepatocellular carcinoma progression via modulation of SREBP1-mediated de novo lipogenesis. Targeting NUPR1-SREBP1/FASN pathway may be a therapeutic alternative for hepatocellular carcinoma.
Annexin A2 plays a key role in protecting against cisplatin-induced AKI through β-catenin/TFEB pathway
Authors: Shen Kunyu , Miao Jinhua , Gao Qiongdan , Ling Xian , Liang Ye , Zhou Qin , Song Qirong , Luo Yuxin , Wu Qinyu , Shen Weiwei , Wang Xiaonan , Li Xiaolong , Liu Youhua , Zhou Shan , Tang Ying , Zhou Lili 
Published: October 2022

AbstractAcute kidney injury (AKI) is in high prevalence in the world. However, the therapeutic strategies for AKI are still in mystery. Studies have shown to improve autophagy and lysosomal function could inhibit AKI. But their modulators need to be explored in detail. Annexin A2 (ANXA2) is a phospholipid-binding protein involving in organelle membrane integrity function, suggesting its important role in autophagy and lysosome homeostasis. It implicates ANXA2 potentially protects against AKI. However, this has not been elucidated. Herein, we found that ANXA2 is increased in renal tubules in cisplatin-induced AKI mice. Ectopic expression of ANXA2 improved lysosomal functions and enhanced autophagic flux, further protecting against renal tubular cell apoptosis and kidney injury. Conversely, knockdown of ANXA2 inhibited lysosomal function and autophagy, which aggravated the progression of AKI. Transcriptome sequencing revealed β-catenin signaling is highly responsible for this process. In vitro, we found ANXA2 induced β-catenin activation, further triggering T-cell factor-4 (TCF4)-induced transcription factor EB (TFEB). Furthermore, TFEB promoted lysosome biogenesis to enhance autophagic flux, resulting in the alleviation of AKI. Our new findings underline ANXA2 is a new therapeutic potential for AKI through modulating autophagy and lysosomal function. The underlying mechanism is associated with its inductive effects on β-catenin/TFEB pathway.
Direct observations of energy transfer from resonant electrons to whistler-mode waves in magnetosheath of Earth
Authors: Kitamura N. , Amano T. , Omura Y. , Boardsen S. A. , Gershman D. J. , Miyoshi Y. , Kitahara M. , Katoh Y. , Kojima H. , Nakamura S. , Shoji M. , Saito Y. , Yokota S. , Giles B. L. , Paterson W. R. , Pollock C. J. , Barrie A. C. , Skeberdis D. G. , Kreisler S. , Le Contel O. , Russell C. T. , Strangeway R. J. , Lindqvist P.-A. , Ergun R. E. , Torbert R. B. , Burch J. L. 
Published: October 2022

AbstractElectromagnetic whistler-mode waves in space plasmas play critical roles in collisionless energy transfer between the electrons and the electromagnetic field. Although resonant interactions have been considered as the likely generation process of the waves, observational identification has been extremely difficult due to the short time scale of resonant electron dynamics. Here we show strong nongyrotropy, which rotate with the wave, of cyclotron resonant electrons as direct evidence for the locally ongoing secular energy transfer from the resonant electrons to the whistler-mode waves using ultra-high temporal resolution data obtained by NASA’s Magnetospheric Multiscale (MMS) mission in the magnetosheath. The nongyrotropic electrons carry a resonant current, which is the energy source of the wave as predicted by the nonlinear wave growth theory. This result proves the nonlinear wave growth theory, and furthermore demonstrates that the degree of nongyrotropy, which cannot be predicted even by that nonlinear theory, can be studied by observations.
A slit-diaphragm-associated protein network for dynamic control of renal filtration
Authors: Kocylowski Maciej K. , Aypek Hande , Bildl Wolfgang , Helmstädter Martin , Trachte Philipp , Dumoulin Bernhard , Wittösch Sina , Kühne Lukas , Aukschun Ute , Teetzen Carolin , Kretz Oliver , Gaal Botond , Kulik Akos , Antignac Corinne , Mollet Geraldine , Köttgen Anna , Göcmen Burulca , Schwenk Jochen , Schulte Uwe , Huber Tobias B. , Fakler Bernd , Grahammer Florian 
Published: October 2022

AbstractThe filtration of blood in the kidney which is crucial for mammalian life is determined by the slit-diaphragm, a cell-cell junction between the foot processes of renal podocytes. The slit-diaphragm is thought to operate as final barrier or as molecular sensor of renal filtration. Using high-resolution proteomic analysis of slit-diaphragms affinity-isolated from rodent kidney, we show that the native slit-diaphragm is built from the junction-forming components Nephrin, Neph1 and Podocin and a co-assembled high-molecular weight network of proteins. The network constituents cover distinct classes of proteins including signaling-receptors, kinases/phosphatases, transporters and scaffolds. Knockout or knock-down of either the core components or the selected network constituents tyrosine kinase MER (MERTK), atrial natriuretic peptide-receptor C (ANPRC), integral membrane protein 2B (ITM2B), membrane-associated guanylate-kinase, WW and PDZ-domain-containing protein1 (MAGI1) and amyloid protein A4 resulted in target-specific impairment or disruption of the filtration process. Our results identify the slit-diaphragm as a multi-component system that is endowed with context-dependent dynamics via a co-assembled protein network.
Laboratory evidence of magnetic reconnection hampered in obliquely interacting flux tubes
Authors: Bolaños Simon , Sladkov Andrey , Smets Roch , Chen Sophia N. , Grisollet Alain , Filippov Evgeny , Henares Jose-Luis , Nastasa Viorel , Pikuz Sergey , Riquier Raphël , Safronova Maria , Severin Alexandre , Starodubtsev Mikhail , Fuchs Julien 
Published: October 2022

AbstractMagnetic reconnection can occur when two plasmas, having anti-parallel components of the magnetic field, encounter each other. In the reconnection plane, the anti-parallel component of the field is annihilated and its energy released in the plasma. Here, we investigate through laboratory experiments the reconnection between two flux tubes that are not strictly anti-parallel. Compression of the anti-parallel component of the magnetic field is observed, as well as a decrease of the reconnection efficiency. Concomitantly, we observe delayed plasma heating and enhanced particle acceleration. Three-dimensional hybrid simulations support these observations and highlight the plasma heating inhibition and reconnection efficiency reduction for these obliquely oriented flux tubes.
Prevalence and mechanisms of evolutionary contingency in human influenza H3N2 neuraminidase
Authors: Lei Ruipeng , Tan Timothy J. C. , Hernandez Garcia Andrea , Wang Yiquan , Diefenbacher Meghan , Teo Chuyun , Gopan Gopika , Tavakoli Dargani Zahra , Teo Qi Wen , Graham Claire S. , Brooke Christopher B. , Nair Satish K. , Wu Nicholas C. 
Published: October 2022

AbstractNeuraminidase (NA) of human influenza H3N2 virus has evolved rapidly and been accumulating mutations for more than half-century. However, biophysical constraints that govern the evolutionary trajectories of NA remain largely elusive. Here, we show that among 70 natural mutations that are present in the NA of a recent human H3N2 strain, >10% are deleterious for an ancestral strain. By mapping the permissive mutations using combinatorial mutagenesis and next-generation sequencing, an extensive epistatic network is revealed. Biophysical and structural analyses further demonstrate that certain epistatic interactions can be explained by non-additive stability effect, which in turn modulates membrane trafficking and enzymatic activity of NA. Additionally, our results suggest that other biophysical mechanisms also contribute to epistasis in NA evolution. Overall, these findings not only provide mechanistic insights into the evolution of human influenza NA and elucidate its sequence-structure-function relationship, but also have important implications for the development of next-generation influenza vaccines.
The N6-methyladenosine methyltransferase METTL16 enables erythropoiesis through safeguarding genome integrity
Authors: Yoshinaga Masanori , Han Kyuho , Morgens David W. , Horii Takuro , Kobayashi Ryosuke , Tsuruyama Tatsuaki , Hia Fabian , Yasukura Shota , Kajiya Asako , Cai Ting , Cruz Pedro H. C. , Vandenbon Alexis , Suzuki Yutaka , Kawahara Yukio , Hatada Izuho , Bassik Michael C. , Takeuchi Osamu 
Published: October 2022

AbstractDuring erythroid differentiation, the maintenance of genome integrity is key for the success of multiple rounds of cell division. However, molecular mechanisms coordinating the expression of DNA repair machinery in erythroid progenitors are poorly understood. Here, we discover that an RNA N6-methyladenosine (m6A) methyltransferase, METTL16, plays an essential role in proper erythropoiesis by safeguarding genome integrity via the control of DNA-repair-related genes. METTL16-deficient erythroblasts exhibit defective differentiation capacity, DNA damage and activation of the apoptotic program. Mechanistically, METTL16 controls m6A deposition at the structured motifs in DNA-repair-related transcripts including Brca2 and Fancm mRNAs, thereby upregulating their expression. Furthermore, a pairwise CRISPRi screen revealed that the MTR4-nuclear RNA exosome complex is involved in the regulation of METTL16 substrate mRNAs in erythroblasts. Collectively, our study uncovers that METTL16 and the MTR4-nuclear RNA exosome act as essential regulatory machinery to maintain genome integrity and erythropoiesis.
Critical role of water structure around interlayer ions for ion storage in layered double hydroxides
Authors: Sudare Tomohito , Yamaguchi Takuro , Ueda Mizuki , Shiiba Hiromasa , Tanaka Hideki , Tipplook Mongkol , Hayashi Fumitaka , Teshima Katsuya 
Published: October 2022

AbstractWater-containing layered materials have found various applications such as water purification and energy storage. The highly structured water molecules around ions under the confinement between the layers determine the ion storage ability. Yet, the relationship between the configuration of interlayer ions and water structure in high ion storage layered materials is elusive. Herein, using layered double hydroxides, we demonstrate that the water structure is sensitive to the filling density of ions in the interlayer space and governs the ion storage. For ion storage of dilute nitrate ions, a 24% decrease in the filling density increases the nitrate storage capacity by 300%. Quartz crystal microbalance with dissipation monitoring studies, combined with multimodal ex situ experiments and theoretical calculations, reveal that the decreasing filling density effectively facilitates the 2D hydrogen-bond networking structure in water around interlayer nitrate ions along with minimal change in the layered structure, leading to the high storage capacity.
Effective screening of Coulomb repulsions in water accelerates reactions of like-charged compounds by orders of magnitude
Authors: Kowalski Adam , Bielec Krzysztof , Bubak Grzegorz , Żuk Pawel J. , Czajkowski Maciej , Sashuk Volodymyr , Huck Wilhelm T. S. , Antosiewicz Jan M. , Holyst Robert 
Published: October 2022

AbstractThe reaction kinetics between like-charged compounds in water is extremely slow due to Coulomb repulsions. Here, we demonstrate that by screening these interactions and, in consequence, increasing the local concentration of reactants, we boost the reactions by many orders of magnitude. The reaction between negatively charged Coenzyme A molecules accelerates ~5 million-fold using cationic micelles. That is ~104 faster kinetics than in 0.5 M NaCl, although the salt is ~106 more concentrated. Rate enhancements are not limited to micelles, as evidenced by significant catalytic effects (104–105-fold) of other highly charged species such as oligomers and polymers. We generalize the observed phenomenon by analogously speeding up a non-covalent complex formation—DNA hybridization. A theoretical analysis shows that the acceleration is correlated to the catalysts’ surface charge density in both experimental systems and enables predicting and controlling reaction rates of like-charged compounds with counter-charged species.
Coexisting divergent and convergent plate boundary assemblages indicate plate tectonics in the Neoarchean
Authors: Huang Bo , Johnson Tim E. , Wilde Simon A. , Polat Ali , Fu Dong , Kusky Timothy 
Published: October 2022

AbstractThe coexistence of divergent (spreading ridge) and convergent (subduction zone) plate boundaries at which lithosphere is respectively generated and destroyed is the hallmark of plate tectonics. Here, we document temporally- and spatially-associated Neoarchean (2.55–2.51 Ga) rock assemblages with mid-ocean ridge and supra-subduction-zone origins from the Angou Complex, southern North China Craton. These assemblages record seafloor spreading and contemporaneous subduction initiation and mature arc magmatism, respectively, analogous to modern divergent and convergent plate boundary processes. Our results provide direct evidence for lateral plate motions in the late Neoarchean, and arguably the operation of plate tectonics, albeit with warmer than average Phanerozoic subduction geotherms. Further, we surmise that plate tectonic processes played an important role in shaping Earth’s surficial environments during the Neoarchean and Paleoproterozoic.
Genetically-informed prediction of short-term Parkinson’s disease progression
Authors: Sadaei Hossein J. , Cordova-Palomera Aldo , Lee Jonghun , Padmanabhan Jaya , Chen Shang-Fu , Wineinger Nathan E. , Dias Raquel , Prilutsky Daria , Szalma Sandor , Torkamani Ali 
Published: October 2022

AbstractParkinson’s disease (PD) treatments modify disease symptoms but have not been shown to slow progression, characterized by gradual and varied motor and non-motor changes overtime. Variation in PD progression hampers clinical research, resulting in long and expensive clinical trials prone to failure. Development of models for short-term PD progression prediction could be useful for shortening the time required to detect disease-modifying drug effects in clinical studies. PD progressors were defined by an increase in MDS-UPDRS scores at 12-, 24-, and 36-months post-baseline. Using only baseline features, PD progression was separately predicted across all timepoints and MDS-UPDRS subparts in independent, optimized, XGBoost models. These predictions plus baseline features were combined into a meta-predictor for 12-month MDS UPDRS Total progression. Data from the Parkinson’s Progression Markers Initiative (PPMI) were used for training with independent testing on the Parkinson’s Disease Biomarkers Program (PDBP) cohort. 12-month PD total progression was predicted with an F-measure 0.77, ROC AUC of 0.77, and PR AUC of 0.76 when tested on a hold-out PPMI set. When tested on PDBP we achieve a F-measure 0.75, ROC AUC of 0.74, and PR AUC of 0.73. Exclusion of genetic predictors led to the greatest loss in predictive accuracy; ROC AUC of 0.66, PR AUC of 0.66–0.68 for both PPMI and PDBP testing. Short-term PD progression can be predicted with a combination of survey-based, neuroimaging, physician examination, and genetic predictors. Dissection of the interplay between genetic risk, motor symptoms, non-motor symptoms, and longer-term expected rates of progression enable generalizable predictions.
Sustainable plant-based ingredients as wheat flour substitutes in bread making
Authors: Wang Yaqin , Jian Ching 
Published: October 2022

AbstractBread as a staple food has been predominantly prepared from refined wheat flour. The world’s demand for food is rising with increased bread consumption in developing countries where climate conditions are unsuitable for wheat cultivation. This reliance on wheat increases the vulnerability to wheat supply shocks caused by force majeure or man-made events, in addition to negative environmental and health consequences. In this review, we discuss the contribution to the sustainability of food systems by partially replacing wheat flour with various types of plant ingredients in bread making, also known as composite bread. The sustainable sources of non-wheat flours, their example use in bread making and potential health and nutritional benefits are summarized. Non-wheat flours pose techno-functional challenges due to significantly different properties of their proteins compared to wheat gluten, and they often contain off-favor compounds that altogether limit the consumer acceptability of final bread products. Therefore, we detail recent advances in processing strategies to improve the sensory and nutritional profiles of composite bread. A special focus is laid on fermentation, for its accessibility and versatility to apply to different ingredients and scenarios. Finally, we outline research needs that require the synergism between sustainability science, human nutrition, microbiomics and food science.
Genome-scale metabolic modeling reveals increased reliance on valine catabolism in clinical isolates of Klebsiella pneumoniae
Authors: Jenior Matthew L. , Dickenson Mary E. , Papin Jason A. 
Published: October 2022

AbstractInfections due to carbapenem-resistant Enterobacteriaceae have recently emerged as one of the most urgent threats to hospitalized patients within the United States and Europe. By far the most common etiological agent of these infections is Klebsiella pneumoniae, frequently manifesting in hospital-acquired pneumonia with a mortality rate of ~50% even with antimicrobial intervention. We performed transcriptomic analysis of data collected previously from in vitro characterization of both laboratory and clinical isolates which revealed shifts in expression of multiple master metabolic regulators across isolate types. Metabolism has been previously shown to be an effective target for antibacterial therapy, and genome-scale metabolic network reconstructions (GENREs) have provided a powerful means to accelerate identification of potential targets in silico. Combining these techniques with the transcriptome meta-analysis, we generated context-specific models of metabolism utilizing a well-curated GENRE of K. pneumoniae (iYL1228) to identify novel therapeutic targets. Functional metabolic analyses revealed that both composition and metabolic activity of clinical isolate-associated context-specific models significantly differs from laboratory isolate-associated models of the bacterium. Additionally, we identified increased catabolism of L-valine in clinical isolate-specific growth simulations. These findings warrant future studies for potential efficacy of valine transaminase inhibition as a target against K. pneumoniae infection.
Amphiphile-CpG vaccination induces potent lymph node activation and COVID-19 immunity in mice and non-human primates
Authors: Seenappa Lochana M. , Jakubowski Aniela , Steinbuck Martin P. , Palmer Erica , Haqq Christopher M. , Carter Crystal , Fontenot Jane , Villinger Francois , McNeil Lisa K. , DeMuth Peter C. 
Published: October 2022

AbstractDespite the success of currently authorized vaccines for the reduction of severe COVID-19 disease risk, rapidly emerging viral variants continue to drive pandemic waves of infection, resulting in numerous global public health challenges. Progress will depend on future advances in prophylactic vaccine activity, including advancement of candidates capable of generating more potent induction of cross-reactive T cells and durable cross-reactive antibody responses. Here we evaluated an Amphiphile (AMP) adjuvant, AMP-CpG, admixed with SARS-CoV-2 Spike receptor binding domain (RBD) immunogen, as a lymph node-targeted protein subunit vaccine (ELI-005) in mice and non-human primates (NHPs). AMP-mediated targeting of CpG DNA to draining lymph nodes resulted in comprehensive local immune activation characterized by extensive transcriptional reprogramming, inflammatory proteomic milieu, and activation of innate immune cells as key orchestrators of antigen-directed adaptive immunity. Prime-boost immunization with AMP-CpG in mice induced potent and durable T cell responses in multiple anatomical sites critical for prophylactic efficacy and prevention of severe disease. Long-lived memory responses were rapidly expanded upon re-exposure to antigen. In parallel, RBD-specific antibodies were long-lived, and exhibited cross-reactive recognition of variant RBD. AMP-CpG-adjuvanted prime-boost immunization in NHPs was safe and well tolerated, while promoting multi-cytokine-producing circulating T cell responses cross-reactive across variants of concern (VOC). Expansion of RBD-specific germinal center (GC) B cells in lymph nodes correlated to rapid seroconversion with variant-specific neutralizing antibody responses exceeding those measured in convalescent human plasma. These results demonstrate the promise of lymph-node adjuvant-targeting to coordinate innate immunity and generate robust adaptive responses critical for vaccine efficacy.
HiFi chromosome-scale diploid assemblies of the grape rootstocks 110R, Kober 5BB, and 101–14 Mgt
Authors: Minio Andrea , Cochetel Noé , Massonnet Mélanie , Figueroa-Balderas Rosa , Cantu Dario 
Published: October 2022

AbstractCultivated grapevines are commonly grafted on closely related species to cope with specific biotic and abiotic stress conditions. The three North American Vitis species V. riparia, V. rupestris, and V. berlandieri, are the main species used for breeding grape rootstocks. Here, we report the diploid chromosome-scale assembly of three widely used rootstocks derived from these species: Richter 110 (110R), Kober 5BB, and 101–14 Millardet et de Grasset (Mgt). Draft genomes of the three hybrids were assembled using PacBio HiFi sequences at an average coverage of 53.1 X-fold. Using the tool suite HaploSync, we reconstructed the two sets of nineteen chromosome-scale pseudomolecules for each genome with an average haploid genome size of 494.5 Mbp. Residual haplotype switches were resolved using shared-haplotype information. These three reference genomes represent a valuable resource for studying the genetic basis of grape adaption to biotic and abiotic stresses, and designing trait-associated markers for rootstock breeding programs.