bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-promoting properties of karyopherin β1 in melanoma by stabilizing Ras-GTPase-activating protein SH3 domain-binding protein 1
Authors: Yang Fan , Li Lin , Mu Zhenzhen , Liu Pengyue , Wang Ying , Zhang Yue , Han Xiuping 
Published: July 2022

AbstractThe nuclear import receptor karyopherin β1 (KPNB1), a member of the Karyopherin protein family, is reported to be overexpressed in various cancers and promote carcinogenesis. By analyzing the correlation between the expression of KPNB1 and the overall survival rate of melanoma patients, we found that melanoma patients with higher expression of KPNB1 had worse survival. Furthermore, the database analyzed that the KPNB1 mRNA level was higher in melanoma samples than that in skin nevus tissues. We thus proposed that KPNB1 played a role in promoting melanoma development, and conducted gain-of- and loss-of-function experiments to test our hypothesis. We found that KPNB1 knockdown significantly retarded the growth and metastasis of melanoma cells in vitro and in vivo, and increased their sensitivity towards the anti-tumor drug cisplatin. KPNB1 overexpression had opposite effects. Notably, in melanoma cells, KPNB1 overexpression significantly decreased Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) protein level, which was also overexpressed in melanoma samples and enhanced malignant behaviors of melanoma cells. We further demonstrated that KPNB1 overexpression induced deubiquitination of G3BP1, and prevented its degradation. However, KPNB1 overexpression hardly affected the nuclear translocation of G3BP1. Additionally, alterations induced by KPNB1 overexpression were partly reversed by G3BP1 inhibition. Therefore, the results suggest that KPNB1 may promote melanoma progression by stabilizing the G3BP1 protein. KPNB1-G3BP1 axis represents a potential therapeutic targetable node for melanoma.
Epigenetically silenced apoptosis-associated tyrosine kinase (AATK) facilitates a decreased expression of Cyclin D1 and WEE1, phosphorylates TP53 and reduces cell proliferation in a kinase-dependent manner
Authors: Woods Michelle L. , Weiss Astrid , Sokol Anna M. , Graumann Johannes , Boettger Thomas , Richter Antje M. , Schermuly Ralph T. , Dammann Reinhard H. 
Published: July 2022

AbstractSilencing of the Apoptosis associated Tyrosine Kinase gene (AATK) has been described in cancer. In our study, we specifically investigated the epigenetic inactivation of AATK in pancreatic adenocarcinoma, lower grade glioma, lung, breast, head, and neck cancer. The resulting loss of AATK correlates with impaired patient survival. Inhibition of DNA methyltransferases (DNMTs) reactivated AATK in glioblastoma and pancreatic cancer. In contrast, epigenetic targeting via the CRISPR/dCas9 system with either EZH2 or DNMT3A inhibited the expression of AATK. Via large-scale kinomic profiling and kinase assays, we demonstrate that AATK acts a Ser/Thr kinase that phosphorylates TP53 at Ser366. Furthermore, whole transcriptome analyses and mass spectrometry associate AATK expression with the GO term ‘regulation of cell proliferation’. The kinase activity of AATK in comparison to the kinase-dead mutant mediates a decreased expression of the key cell cycle regulators Cyclin D1 and WEE1. Moreover, growth suppression through AATK relies on its kinase activity. In conclusion, the Ser/Thr kinase AATK represses growth and phosphorylates TP53. Furthermore, expression of AATK was correlated with a better patient survival for different cancer entities. This data suggests that AATK acts as an epigenetically inactivated tumor suppressor gene.
XAF1 drives apoptotic switch of endoplasmic reticulum stress response through destabilization of GRP78 and CHIP
Authors: Lee Kyung-Woo , Hong Hui-Ra , Lim Ji-Sun , Ko Kyung-Phil , Lee Min-Goo , Chi Sung-Gil 
Published: July 2022

AbstractX-linked inhibitor of apoptosis-associated factor-1 (XAF1) is a stress-inducible tumor suppressor that is commonly inactivated in many human cancers. Despite accumulating evidence for the pro-apoptotic role for XAF1 under various stressful conditions, its involvement in endoplasmic reticulum (ER) stress response remains undefined. Here, we report that XAF1 increases cell sensitivity to ER stress and acts as a molecular switch in unfolded protein response (UPR)-mediated cell-fate decisions favoring apoptosis over adaptive autophagy. Mechanistically, XAF1 interacts with and destabilizes ER stress sensor GRP78 through the assembly of zinc finger protein 313 (ZNF313)-mediated destruction complex. Moreover, XAF1 expression is activated through PERK-Nrf2 signaling and destabilizes C-terminus of Hsc70-interacting protein (CHIP) ubiquitin E3 ligase, thereby blocking CHIP-mediated K63-linked ubiquitination and subsequent phosphorylation of inositol-required enzyme-1α (IRE1α) that is involved in in the adaptive ER stress response. In tumor xenograft assays, XAF1−/− tumors display substantially lower regression compared to XAF1+/+ tumors in response to cytotoxic dose of ER stress inducer. XAF1 and GRP78 expression show an inverse correlation in human cancer cell lines and primary breast carcinomas. Collectively this study uncovers an important role for XAF1 as a linchpin to govern the sensitivity to ER stress and the outcomes of UPR signaling, illuminating the mechanistic consequence of XAF1 inactivation in tumorigenesis.
Topological digestion drives time-varying rheology of entangled DNA fluids
Authors: Michieletto D. , Neill P. , Weir S. , Evans D. , Crist N. , Martinez V. A. , Robertson-Anderson R. M. 
Published: July 2022

AbstractUnderstanding and controlling the rheology of polymeric complex fluids that are pushed out-of-equilibrium is a fundamental problem in both industry and biology. For example, to package, repair, and replicate DNA, cells use enzymes to constantly manipulate DNA topology, length, and structure. Inspired by this feat, here we engineer and study DNA-based complex fluids that undergo enzymatically-driven topological and architectural alterations via restriction endonuclease (RE) reactions. We show that these systems display time-dependent rheological properties that depend on the concentrations and properties of the comprising DNA and REs. Through time-resolved microrheology experiments and Brownian Dynamics simulations, we show that conversion of supercoiled to linear DNA topology leads to a monotonic increase in viscosity. On the other hand, the viscosity of entangled linear DNA undergoing fragmentation displays a universal decrease that we rationalise using living polymer theory. Finally, to showcase the tunability of these behaviours, we design a DNA fluid that exhibits a time-dependent increase, followed by a temporally-gated decrease, of its viscosity. Our results present a class of polymeric fluids that leverage naturally occurring enzymes to drive diverse time-varying rheology by performing architectural alterations to the constituents.
Sustainable environmental remediation via biomimetic multifunctional lignocellulosic nano-framework
Authors: Li Jinghao , Li Xiaohan , Da Yabin , Yu Jiali , Long Bin , Zhang Peng , Bakker Christopher , McCarl Bruce A. , Yuan Joshua S. , Dai Susie Y. 
Published: July 2022

AbstractChemical pollution threatens human health and ecosystem sustainability. Persistent organic pollutants (POPs) like per- and polyfluoroalkyl substances (PFAS) are expensive to clean up once emitted. Innovative and synergistic strategies are urgently needed, yet process integration and cost-effectiveness remain challenging. An in-situ PFAS remediation system is developed to employ a plant-derived biomimetic nano-framework to achieve highly efficient adsorption and subsequent fungal biotransformation synergistically. The multiple component framework is presented as Renewable Artificial Plant for In-situ Microbial Environmental Remediation (RAPIMER). RAPIMER exhibits high adsorption capacity for the PFAS compounds and diverse adsorption capability toward co-contaminants. Subsequently, RAPIMER provides the substrates and contaminants for in situ bioremediation via fungus Irpex lacteus and promotes PFAS detoxification. RAPIMER arises from cheap lignocellulosic sources, enabling a broader impact on sustainability and a means for low-cost pollutant remediation.
High-temperature flexible WSe2 photodetectors with ultrahigh photoresponsivity
Authors: Zou Yixuan , Zhang Zekun , Yan Jiawen , Lin Linhan , Huang Guanyao , Tan Yidong , You Zheng , Li Peng 
Published: July 2022

AbstractThe development of high-temperature photodetectors can be beneficial for numerous applications, such as aerospace engineering, military defence and harsh-environments robotics. However, current high-temperature photodetectors are characterized by low photoresponsivity (<10 A/W) due to the poor optical sensitivity of commonly used heat-resistant materials. Here, we report the realization of h-BN-encapsulated graphite/WSe2 photodetectors which can endure temperatures up to 700 °C in air (1000 °C in vacuum) and exhibit unconventional negative photoconductivity (NPC) at high temperatures. Operated in NPC mode, the devices show a photoresponsivity up to 2.2 × 106 A/W, which is ~5 orders of magnitude higher than that of state-of-the-art high-temperature photodetectors. Furthermore, our devices demonstrate good flexibility, making it highly adaptive to various shaped surfaces. Our approach can be extended to other 2D materials and may stimulate further developments of 2D optoelectronic devices operating in harsh environments.
Pressure-induced monotonic enhancement of Tc to over 30 K in superconducting Pr0.82Sr0.18NiO2 thin films
Authors: Wang N. N. , Yang M. W. , Yang Z. , Chen K. Y. , Zhang H. , Zhang Q. H. , Zhu Z. H. , Uwatoko Y. , Gu L. , Dong X. L. , Sun J. P. , Jin K. J. , Cheng J.-G. 
Published: July 2022

AbstractThe successful synthesis of superconducting infinite-layer nickelate thin films with the highest Tc ≈ 15 K has ignited great enthusiasm for this material class as potential analogs of the high-Tc cuprates. Pursuing a higher Tc is always an imperative task in studying a new superconducting material system. Here we report high-quality Pr0.82Sr0.18NiO2 thin films with Tconset ≈ 17 K synthesized by carefully tuning the amount of CaH2 in the topotactic chemical reduction and the effect of pressure on its superconducting properties by measuring electrical resistivity under various pressures in a cubic anvil cell apparatus. We find that the onset temperature of the superconductivity, Tconset, can be enhanced monotonically from ~17 K at ambient pressure to ~31 K at 12.1 GPa without showing signatures of saturation upon increasing pressure. This encouraging result indicates that the Tc of infinite-layer nickelates superconductors still has room to go higher and it can be further boosted by applying higher pressures or strain engineering in the heterostructure films.
Metaplastic and energy-efficient biocompatible graphene artificial synaptic transistors for enhanced accuracy neuromorphic computing
Authors: Kireev Dmitry , Liu Samuel , Jin Harrison , Patrick Xiao T. , Bennett Christopher H. , Akinwande Deji , Incorvia Jean Anne C. 
Published: July 2022

AbstractCMOS-based computing systems that employ the von Neumann architecture are relatively limited when it comes to parallel data storage and processing. In contrast, the human brain is a living computational signal processing unit that operates with extreme parallelism and energy efficiency. Although numerous neuromorphic electronic devices have emerged in the last decade, most of them are rigid or contain materials that are toxic to biological systems. In this work, we report on biocompatible bilayer graphene-based artificial synaptic transistors (BLAST) capable of mimicking synaptic behavior. The BLAST devices leverage a dry ion-selective membrane, enabling long-term potentiation, with ~50 aJ/µm2 switching energy efficiency, at least an order of magnitude lower than previous reports on two-dimensional material-based artificial synapses. The devices show unique metaplasticity, a useful feature for generalizable deep neural networks, and we demonstrate that metaplastic BLASTs outperform ideal linear synapses in classic image classification tasks. With switching energy well below the 1 fJ energy estimated per biological synapse, the proposed devices are powerful candidates for bio-interfaced online learning, bridging the gap between artificial and biological neural networks.
A unique class of Zn2+-binding serine-based PBPs underlies cephalosporin resistance and sporogenesis in Clostridioides difficile
Authors: Sacco Michael D. , Wang Shaohui , Adapa Swamy R. , Zhang Xiujun , Lewandowski Eric M. , Gongora Maura V. , Keramisanou Dimitra , Atlas Zachary D. , Townsend Julia A. , Gatdula Jean R. , Morgan Ryan T. , Hammond Lauren R. , Marty Michael T. , Wang Jun , Eswara Prahathees J. , Gelis Ioannis , Jiang Rays H. Y. , Sun Xingmin , Chen Yu 
Published: July 2022

AbstractTreatment with β-lactam antibiotics, particularly cephalosporins, is a major risk factor forClostridioides difficileinfection. These broad-spectrum antibiotics irreversibly inhibit penicillin-binding proteins (PBPs), which are serine-based enzymes that assemble the bacterial cell wall. However,C. difficilehas four different PBPs (PBP1-3 and SpoVD) with various roles in growth and spore formation, and their specific links to β-lactam resistance in this pathogen are underexplored. Here, we show that PBP2 (known to be essential for vegetative growth) is the primary bactericidal target for β-lactams inC. difficile. PBP2 is insensitive to cephalosporin inhibition, and this appears to be the main basis for cephalosporin resistance in this organism. We determine crystal structures ofC. difficilePBP2, alone and in complex with β-lactams, revealing unique features including ligand-induced conformational changes and an active site Zn2+-binding motif that influences β-lactam binding and protein stability. The Zn2+-binding motif is also present inC. difficilePBP3 and SpoVD (which are known to be essential for sporulation), as well as in other bacterial taxa including species living in extreme environments and the human gut. We speculate that this thiol-containing motif and its cognate Zn2+might function as a redox sensor to regulate cell wall synthesis for survival in adverse or anaerobic environments.
TidyMass an object-oriented reproducible analysis framework for LC–MS data
Authors: Shen Xiaotao , Yan Hong , Wang Chuchu , Gao Peng , Johnson Caroline H. , Snyder Michael P. 
Published: July 2022

AbstractReproducibility, traceability, and transparency have been long-standing issues for metabolomics data analysis. Multiple tools have been developed, but limitations still exist. Here, we present the tidyMass project (https://www.tidymass.org/), a comprehensive R-based computational framework that can achieve the traceable, shareable, and reproducible workflow needs of data processing and analysis for LC-MS-based untargeted metabolomics. TidyMass is an ecosystem of R packages that share an underlying design philosophy, grammar, and data structure, which provides a comprehensive, reproducible, and object-oriented computational framework. The modular architecture makes tidyMass a highly flexible and extensible tool, which other users can improve and integrate with other tools to customize their own pipeline.
Mesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta
Authors: Chandrakanthan Vashe , Rorimpandey Prunella , Zanini Fabio , Chacon Diego , Olivier Jake , Joshi Swapna , Kang Young Chan , Knezevic Kathy , Huang Yizhou , Qiao Qiao , Oliver Rema A. , Unnikrishnan Ashwin , Carter Daniel R. , Lee Brendan , Brownlee Chris , Power Carl , Brink Robert , Mendez-Ferrer Simon , Enikolopov Grigori , Walsh William , Göttgens Berthold , Taoudi Samir , Beck Dominik , Pimanda John E. 
Published: July 2022

AbstractMouse haematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5), on the ventral surface of the dorsal aorta, by endothelial-to-haematopoietic transition. We investigated whether mesenchymal stem cells, which provide an essential niche for long-term HSCs (LT-HSCs) in the bone marrow, reside in the aorta–gonad–mesonephros and contribute to the development of the dorsal aorta and endothelial-to-haematopoietic transition. Here we show that mesoderm-derived PDGFRA+stromal cells (Mesp1derPSCs) contribute to the haemogenic endothelium of the dorsal aorta and populate the E10.5–E11.5 aorta–gonad–mesonephros but by E13.5 were replaced by neural-crest-derived PSCs (Wnt1derPSCs). Co-aggregating non-haemogenic endothelial cells withMesp1derPSCs but notWnt1derPSCs resulted in activation of a haematopoietic transcriptional programme in endothelial cells and generation of LT-HSCs. Dose-dependent inhibition of PDGFRA or BMP, WNT and NOTCH signalling interrupted this reprogramming event. Together, aorta–gonad–mesonephrosMesp1derPSCs could potentially be harnessed to manufacture LT-HSCs from endothelium.
Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-bet+ B cells
Authors: Csomos Krisztian , Ujhazi Boglarka , Blazso Peter , Herrera Jose L. , Tipton Christopher M. , Kawai Tomoki , Gordon Sumai , Ellison Maryssa , Wu Kevin , Stowell Matthew , Haynes Lauren , Cruz Rachel , Zakota Bence , Nguyen Johnny , Altrich Michelle , Geier Christoph B. , Sharapova Svetlana , Dasso Joseph F. , Leiding Jennifer W. , Smith Grace , Al-Herz Waleed , de Barros Dorna Mayra , Fadugba Olajumoke , Fronkova Eva , Kanderova Veronika , Svaton Michael , Henrickson Sarah E. , Hernandez Joseph D. , Kuijpers Taco , Kandilarova Snezhina Mihailova , Naumova Elizaveta , Milota Tomas , Sediva Anna , Moshous Despina , Neven Benedicte , Saco Tara , Sargur Ravishankar , Savic Sinisa , Sleasman John , Sunkersett Gauri , Ward Brant R. , Komatsu Masanobu , Pittaluga Stefania , Kumanovics Attila , Butte Manish J. , Cancro Michael P. , Pillai Shiv , Meffre Eric , Notarangelo Luigi D. , Walter Jolan E. 
Published: July 2022

AbstractThe recombination-activating genes (RAG) 1 and 2 are indispensable for diversifying the primary B cell receptor repertoire and pruning self-reactive clones via receptor editing in the bone marrow; however, the impact ofRAG1/RAG2on peripheral tolerance is unknown. Partial RAG deficiency (pRD) manifesting with late-onset immune dysregulation represents an ‘experiment of nature’ to explore this conundrum. By studying B cell development and subset-specific repertoires in pRD, we demonstrate that reduced RAG activity impinges on peripheral tolerance through the generation of a restricted primary B cell repertoire, persistent antigenic stimulation and an inflammatory milieu with elevated B cell-activating factor. This unique environment gradually provokes profound B cell dysregulation with widespread activation, remarkable extrafollicular maturation and persistence, expansion and somatic diversification of self-reactive clones. Through the model of pRD, we reveal aRAG-dependent ‘domino effect’ that impacts stringency of tolerance and B cell fate in the periphery.
High-resolution Digital Surface Model of the 2021 eruption deposit of Cumbre Vieja volcano, La Palma, Spain
Authors: Civico Riccardo , Ricci Tullio , Scarlato Piergiorgio , Taddeucci Jacopo , Andronico Daniele , Del Bello Elisabetta , D’Auria Luca , Hernández Pedro A. , Pérez Nemesio M. 
Published: July 2022

AbstractIdentifying accurate topographic variations associated with volcanic eruptions plays a key role in obtaining information on eruptive parameters, volcano structure, input data for volcano processes modelling, and civil protection and recovery actions. The 2021 eruption of Cumbre Vieja volcano is the largest eruptive event in the recorded history for La Palma Island. Over the course of almost 3 months, the volcano produced profound morphological changes in the landscape affecting both the natural and the anthropic environment over an area of tens of km2. We present the results of a UAS (Unoccupied Aircraft System) survey consisting of >12,000 photographs coupled with Structure-from-Motion photogrammetry that allowed us to produce a very-high-resolution (0.2 m/pixel) Digital Surface Model (DSM). We characterised the surface topography of the newly formed volcanic landforms and produced an elevation difference map by differencing our survey and a pre-event surface, identifying morphological changes in detail. The present DSM, the first one with such a high resolution to our knowledge, represents a relevant contribution to both the scientific community and the local authorities.
Effect of cytokine-induced alterations in extracellular matrix composition on diabetic retinopathy-relevant endothelial cell behaviors
Authors: Giblin Meredith J. , Ontko Cayla D. , Penn John S. 
Published: July 2022

AbstractRetinal vascular basement membrane (BM) thickening is an early structural abnormality of diabetic retinopathy (DR). Recent studies suggest that BM thickening contributes to the DR pathological cascade; however, much remains to be elucidated about the exact mechanisms by which BM thickening develops and subsequently drives other pathogenic events in DR. Therefore, we undertook a systematic analysis to understand how human retinal microvascular endothelial cells (hRMEC) and human retinal pericytes (hRP) change their expression of key extracellular matrix (ECM) constituents when treated with diabetes-relevant stimuli designed to model the three major insults of the diabetic environment: hyperglycemia, dyslipidemia, and inflammation. TNFα and IL-1β caused the most potent and consistent changes in ECM expression in both hRMEC and hRP. We also demonstrate that conditioned media from IL-1β-treated human Müller cells caused dose-dependent, significant increases in collagen IV and agrin expression in hRMEC. After narrowing our focus to inflammation-induced changes, we sought to understand how ECM deposited by hRMEC and hRP under inflammatory conditions affects the behavior of naïve hRMEC. Our data demonstrated that diabetes-relevant alterations in ECM composition alone cause both increased adhesion molecule expression by and increased peripheral blood mononuclear cell (PBMC) adhesion to naïve hRMEC. Taken together, these data demonstrate novel roles for inflammation and pericytes in driving BM pathology and suggest that inflammation-induced ECM alterations may advance other pathogenic behaviors in DR, including leukostasis.
Factors associated with the differential distribution of cetaceans linked with deep habitats in the Western Mediterranean Sea
Authors: Torreblanca Estefanía , Báez José-Carlos , Real Raimundo , Macías David , García-Barcelona Salvador , Ferri-Yañez Francisco , Camiñas Juan-Antonio 
Published: July 2022

AbstractDeep-habitat cetaceans are generally difficult to study, leading to a limited knowledge of their population. This paper assesses the differential distribution patterns of three deep-habitat cetaceans (Sperm whale—Physeter macrocephalus,Risso’s dolphin—Grampus griseus &Cuvier’s beaked whale—Ziphius cavirostris). We used data of 842 opportunistic sightings of cetaceans in the western Mediterranean sea. We inferred environmental and spatio-temporal factors that affect their distribution. Binary logistic regression models were generated to compare the presence of deep-habitat cetaceans with the presence of other cetacean species in the dataset. Then, the favourability function was applied, allowing for comparison between all the models. Sperm whale and Risso’s dolphin presence was differentially favoured by the distance to towns in the eastern part of the western Mediterranean sea. The differential distribution of sperm whale was also influenced by the stability of SST, and that of the Risso’s dolphin by lower mean salinity and higher mean Chlorophyll A concentration. When modelling the three deep-habitat cetaceans (including Cuvier’s beaked whale), the variable distance to towns had a negative influence on the presence of any of them more than it did to other cetaceans, being more favourable far from towns, so this issue should be further investigated.