bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis
Authors: Pan Yuchen , Li Jingman , Wang Jiali , Jiang Qi , Yang Jingjing , Dou Huan , Liang Huaping , Li Kuanyu , Hou Yayi 
Published: September 2022

AbstractThe therapeutic effect of mesenchymal stem cells (MSCs) on sepsis has been well-known. However, a comprehensive understanding of the relationship between MSCs and macrophages remains elusive. Superparamagnetic iron oxide (SPIO) is one of the most commonly used tracers for MSCs. Our previous study has shown that SPIO enhanced the therapeutic effect of MSCs in a macrophage-dependent manner. However, the fate of SPIO-labeled MSCs (MSCSPIO) after infusion remains unknown and the direct interaction between MSCSPIO and macrophages remains unclear. Mice were injected intravenously with MSCSPIO at 2 h after Escherichia coli infection and sacrificed at different times to investigate their distribution and therapeutic effect. We found that MSCSPIO homed to lungs rapidly after infusion and then trapped in livers for more than 10 days. Only a few MSCSPIO homed to the spleen and there was no MSCSPIO detectable in the brain, heart, kidney, colon, and uterus. MSCSPIO tended to stay longer in injured organs compared with healthy organs and played a long-term protective role in sepsis. The mRNA expression profiles between MSCs and MSCSPIO were rather different, genes related to lipid metabolism, inflammation, and oxidative stress were changed. The levels of ROS and lipid peroxide were elevated in MSCSPIO, which confirmed that SPIO-induced ferroptosis in MSCSPIO. Ferroptosis of MSCSPIO induced by SPIO enhanced the efferocytosis of macrophages and thus enhanced the protective effect on septic mice, while the benefits were impaired after MSCSPIO were treated with Ferrostatin-1 (Fer-1) or Liproxtatin-1 (Lip-1), the inhibitors of ferroptosis. SPIO-induced ferroptosis in MSCs contributes to better therapeutic effects in sepsis by enhancing the efferocytosis of macrophages. Our data showed the efficacy and advantage of MSCSPIO as a therapeutic tool and the cell states exert different curative effects on sepsis.
A dual Keap1 and p47phox inhibitor Ginsenoside Rb1 ameliorates high glucose/ox-LDL-induced endothelial cell injury and atherosclerosis
Authors: Wang Zi-Chao , Niu Kai-Ming , Wu Yu-Jie , Du Kai-Rui , Qi Lian-Wen , Zhou Ye-Bo , Sun Hai-Jian 
Published: September 2022

AbstractOxidative stress is a vital contributor to the development and progression of diabetes-accelerated atherosclerosis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known molecule that participates in cellular defense against oxidative stress. Utilizing luciferase reporter assay from 379 natural products, we reported here that Ginsenoside Rb1 played a dual role in inhibiting Kelch-like ECH-associated protein 1 (Keap1) and p47phox luciferase reporter activities. In endothelial cells (ECs), Rb1 pretreatment enhanced cell viability, reduced oxidative stress, inflammation, endothelial-mesenchymal transition (EndMT), and apoptosis, as well as ameliorated mitochondrial quality following oxidized low-density lipoprotein (ox-LDL) plus high glucose (HG) challenge. Rb1 directly bound to Keap1 and promoted its ubiquitination and proteasomal degradation dependent on lysine residues (K108, K323, and K551) by recruiting the E3 ligase synovial apoptosis inhibitor 1 (SYVN1), leading to Nrf2 dissociation from Keap1, Nrf2 nuclear translocation, Nrf2/PGC-1α complex formation. We further identified that Rb1 could bind to p47phox and reduce its phosphorylation and membrane translocation, thereby disrupting the assembly of the NOX2 complex. Importantly, Rb1-mediated preservation of cytoplasmic p47phox stabilized and contributed to Nrf2 activation. Additionally, we revealed that Rb1 reduced aortic atherosclerotic plaque formation along with reductions in oxidative stress and inflammatory response in streptozotocin (STZ)-induced ApoE−/− mice, but not in ApoE−/− mice with deficiency of Nrf2 and PGC-1α. Collectively, we demonstrated that Rb1, which directly targeted Keap1 and p47phox in ECs, may be an attractive candidate for the treatment of atherosclerosis in diabetes.
Tracking 21st century anthropogenic and natural carbon fluxes through model-data integration
Authors: Bultan Selma , Nabel Julia E. M. S. , Hartung Kerstin , Ganzenmüller Raphael , Xu Liang , Saatchi Sassan , Pongratz Julia 
Published: September 2022

AbstractMonitoring the implementation of emission commitments under the Paris agreement relies on accurate estimates of terrestrial carbon fluxes. Here, we assimilate a 21st century observation-based time series of woody vegetation carbon densities into a bookkeeping model (BKM). This approach allows us to disentangle the observation-based carbon fluxes by terrestrial woody vegetation into anthropogenic and environmental contributions. Estimated emissions (from land-use and land cover changes) between 2000 and 2019 amount to 1.4 PgC yr−1, reducing the difference to other carbon cycle model estimates by up to 88% compared to previous estimates with the BKM (without the data assimilation). Our estimates suggest that the global woody vegetation carbon sink due to environmental processes (1.5 PgC yr−1) is weaker and more susceptible to interannual variations and extreme events than estimated by state-of-the-art process-based carbon cycle models. These findings highlight the need to advance model-data integration to improve estimates of the terrestrial carbon cycle under the Global Stocktake.
Classical center-surround receptive fields facilitate novel object detection in retinal bipolar cells
Authors: Gaynes John A. , Budoff Samuel A. , Grybko Michael J. , Hunt Joshua B. , Poleg-Polsky Alon 
Published: September 2022

AbstractAntagonistic interactions between center and surround receptive field (RF) components lie at the heart of the computations performed in the visual system. Circularly symmetric center-surround RFs are thought to enhance responses to spatial contrasts (i.e., edges), but how visual edges affect motion processing is unclear. Here, we addressed this question in retinal bipolar cells, the first visual neuron with classic center-surround interactions. We found that bipolar glutamate release emphasizes objects that emerge in the RF; their responses to continuous motion are smaller, slower, and cannot be predicted by signals elicited by stationary stimuli. In our hands, the alteration in signal dynamics induced by novel objects was more pronounced than edge enhancement and could be explained by priming of RF surround during continuous motion. These findings echo the salience of human visual perception and demonstrate an unappreciated capacity of the center-surround architecture to facilitate novel object detection and dynamic signal representation.
Center-surround interactions underlie bipolar cell motion sensitivity in the mouse retina
Authors: Strauss Sarah , Korympidou Maria M. , Ran Yanli , Franke Katrin , Schubert Timm , Baden Tom , Berens Philipp , Euler Thomas , Vlasits Anna L. 
Published: September 2022

AbstractMotion sensing is a critical aspect of vision. We studied the representation of motion in mouse retinal bipolar cells and found that some bipolar cells are radially direction selective, preferring the origin of small object motion trajectories. Using a glutamate sensor, we directly observed bipolar cells synaptic output and found that there are radial direction selective and non-selective bipolar cell types, the majority being selective, and that radial direction selectivity relies on properties of the center-surround receptive field. We used these bipolar cell receptive fields along with connectomics to design biophysical models of downstream cells. The models and additional experiments demonstrated that bipolar cells pass radial direction selective excitation to starburst amacrine cells, which contributes to their directional tuning. As bipolar cells provide excitation to most amacrine and ganglion cells, their radial direction selectivity may contribute to motion processing throughout the visual system.
Circulating multimeric immune complexes contribute to immunopathology in COVID-19
Authors: Ankerhold Jakob , Giese Sebastian , Kolb Philipp , Maul-Pavicic Andrea , Voll Reinhard E. , Göppert Nathalie , Ciminski Kevin , Kreutz Clemens , Lother Achim , Salzer Ulrich , Bildl Wolfgang , Welsink Tim , Morgenthaler Nils G. , Grawitz Andrea Busse , Emmerich Florian , Steinmann Daniel , Huzly Daniela , Schwemmle Martin , Hengel Hartmut , Falcone Valeria 
Published: September 2022

AbstractA dysregulated immune response with high levels of SARS-CoV-2 specific IgG antibodies characterizes patients with severe or critical COVID-19. Although a robust IgG response is considered to be protective, excessive triggering of activating Fc-gamma-receptors (FcγRs) could be detrimental and cause immunopathology. Here, we document excessive FcγRIIIA/CD16A activation in patients developing severe or critical COVID-19 but not in those with mild disease. We identify two independent ligands mediating extreme FcγRIIIA/CD16A activation. Soluble circulating IgG immune complexes (sICs) are detected in about 80% of patients with severe and critical COVID-19 at levels comparable to active systemic lupus erythematosus (SLE) disease. FcγRIIIA/CD16A activation is further enhanced by afucosylation of SARS-CoV-2 specific IgG. Utilizing cell-based reporter systems we provide evidence that sICs can be formed prior to a specific humoral response against SARS-CoV-2. Our data suggest a cycle of immunopathology driven by an early formation of sICs in predisposed patients. These findings suggest a reason for the seemingly paradoxical findings of high antiviral IgG responses and systemic immune dysregulation in severe COVID-19. The involvement of circulating sICs in the promotion of immunopathology in predisposed patients opens new possibilities for intervention strategies to mitigate critical COVID-19 progression.
McaA and McaB control the dynamic positioning of a bacterial magnetic organelle
Authors: Wan Juan , Monteil Caroline L. , Taoka Azuma , Ernie Gabriel , Park Kieop , Amor Matthieu , Taylor-Cornejo Elias , Lefevre Christopher T. , Komeili Arash 
Published: September 2022

AbstractMagnetotactic bacteria are a diverse group of microorganisms that use intracellular chains of ferrimagnetic nanocrystals, produced within magnetosome organelles, to align and navigate along the geomagnetic field. Several conserved genes for magnetosome formation have been described, but the mechanisms leading to distinct species-specific magnetosome chain configurations remain unclear. Here, we show that the fragmented nature of magnetosome chains in Magnetospirillum magneticum AMB-1 is controlled by genes mcaA and mcaB. McaA recognizes the positive curvature of the inner cell membrane, while McaB localizes to magnetosomes. Along with the MamK actin-like cytoskeleton, McaA and McaB create space for addition of new magnetosomes in between pre-existing magnetosomes. Phylogenetic analyses suggest that McaA and McaB homologs are widespread among magnetotactic bacteria and may represent an ancient strategy for magnetosome positioning.
Modeling tissue-specific breakpoint proximity of structural variations from whole-genomes to identify cancer drivers
Authors: Martinez-Fundichely Alexander , Dixon Austin , Khurana Ekta 
Published: September 2022

AbstractStructural variations (SVs) in cancer cells often impact large genomic regions with functional consequences. However, identification of SVs under positive selection is a challenging task because little is known about the genomic features related to the background breakpoint distribution in different cancers. We report a method that uses a generalized additive model to investigate the breakpoint proximity curves from 2,382 whole-genomes of 32 cancer types. We find that a multivariate model, which includes linear and nonlinear partial contributions of various tissue-specific features and their interaction terms, can explain up to 57% of the observed deviance of breakpoint proximity. In particular, three-dimensional genomic features such as topologically associating domains (TADs), TAD-boundaries and their interaction with other features show significant contributions. The model is validated by identification of known cancer genes and revealed putative drivers in cancers different than those with previous evidence of positive selection.
Redβ177 annealase structure reveals details of oligomerization and λ Red-mediated homologous DNA recombination
Authors: Newing Timothy P. , Brewster Jodi L. , Fitschen Lucy J. , Bouwer James C. , Johnston Nikolas P. , Yu Haibo , Tolun Gökhan 
Published: September 2022

AbstractThe Redβ protein of the bacteriophage λ red recombination system is a model annealase which catalyzes single-strand annealing homologous DNA recombination. Here we present the structure of a helical oligomeric annealing intermediate of Redβ, consisting of N-terminal residues 1-177 bound to two complementary 27mer oligonucleotides, determined via cryogenic electron microscopy (cryo-EM) to a final resolution of 3.3 Å. The structure reveals a continuous binding groove which positions and stabilizes complementary DNA strands in a planar orientation to facilitate base pairing via a network of hydrogen bonding. Definition of the inter-subunit interface provides a structural basis for the propensity of Redβ to oligomerize into functionally significant long helical filaments, a trait shared by most annealases. Our cryo-EM structure and molecular dynamics simulations suggest that residues 133-138 form a flexible loop which modulates access to the binding groove. More than half a century after its discovery, this combination of structural and computational observations has allowed us to propose molecular mechanisms for the actions of the model annealase Redβ, a defining member of the Redβ/RecT protein family.
Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis
Authors: Jaeger Benedikt , Schupp Jonas Christian , Plappert Linda , Terwolbeck Oliver , Artysh Nataliia , Kayser Gian , Engelhard Peggy , Adams Taylor Sterling , Zweigerdt Robert , Kempf Henning , Lienenklaus Stefan , Garrels Wiebke , Nazarenko Irina , Jonigk Danny , Wygrecka Malgorzata , Klatt Denise , Schambach Axel , Kaminski Naftali , Prasse Antje 
Published: September 2022

AbstractIdiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. In this study, we focus on the properties of airway basal cells (ABC) obtained from patients with IPF (IPF-ABC). Single cell RNA sequencing (scRNAseq) of bronchial brushes revealed extensive reprogramming of IPF-ABC towards a KRT17high PTENlow dedifferentiated cell type. In the 3D organoid model, compared to ABC obtained from healthy volunteers, IPF-ABC give rise to more bronchospheres, de novo bronchial structures resembling lung developmental processes, induce fibroblast proliferation and extracellular matrix deposition in co-culture. Intratracheal application of IPF-ABC into minimally injured lungs of Rag2−/− or NRG mice causes severe fibrosis, remodeling of the alveolar compartment, and formation of honeycomb cyst-like structures. Connectivity MAP analysis of scRNAseq of bronchial brushings suggested that gene expression changes in IPF-ABC can be reversed by SRC inhibition. After demonstrating enhanced SRC expression and activity in these cells, and in IPF lungs, we tested the effects of saracatinib, a potent SRC inhibitor previously studied in humans. We demonstrate that saracatinib modified in-vitro and in-vivo the profibrotic changes observed in our 3D culture system and novel mouse xenograft model.
Battery-free wireless imaging of underwater environments
Authors: Afzal Sayed Saad , Akbar Waleed , Rodriguez Osvy , Doumet Mario , Ha Unsoo , Ghaffarivardavagh Reza , Adib Fadel 
Published: September 2022

AbstractImaging underwater environments is of great importance to marine sciences, sustainability, climatology, defense, robotics, geology, space exploration, and food security. Despite advances in underwater imaging, most of the ocean and marine organisms remain unobserved and undiscovered. Existing methods for underwater imaging are unsuitable for scalable, long-term, in situ observations because they require tethering for power and communication. Here we describe underwater backscatter imaging, a method for scalable, real-time wireless imaging of underwater environments using fully-submerged battery-free cameras. The cameras power up from harvested acoustic energy, capture color images using ultra-low-power active illumination and a monochrome image sensor, and communicate wirelessly at net-zero-power via acoustic backscatter. We demonstrate wireless battery-free imaging of animals, plants, pollutants, and localization tags in enclosed and open-water environments. The method’s self-sustaining nature makes it desirable for massive, continuous, and long-term ocean deployments with many applications including marine life discovery, submarine surveillance, and underwater climate change monitoring.
Structural insights into molecular mechanism for N6-adenosine methylation by MT-A70 family methyltransferase METTL4
Authors: Luo Qiang , Mo Jiezhen , Chen Hao , Hu Zetao , Wang Baihui , Wu Jiabing , Liang Ziyu , Xie Wenhao , Du Kangxi , Peng Maolin , Li Yingping , Li Tianyang , Zhang Yangyi , Shi Xiaoyan , Shen Wen-Hui , Shi Yang , Dong Aiwu , Wang Hailin , Ma Jinbiao 
Published: September 2022

AbstractMETTL4 belongs to a subclade of MT-A70 family members of methyltransferase (MTase) proteins shown to mediate N6-adenosine methylation for both RNA and DNA in diverse eukaryotes. Here, we report that Arabidopsis METTL4 functions as U2 snRNA MTase for N6−2’-O-dimethyladenosine (m6Am) in vivo that regulates flowering time, and specifically catalyzes N6-methylation of 2’-O-methyladenosine (Am) within a single-stranded RNA in vitro. The apo structures of full-length Arabidopsis METTL4 bound to S-adenosyl-L-methionine (SAM) and the complex structure with an Am-containing RNA substrate, combined with mutagenesis and in vitro enzymatic assays, uncover a preformed L-shaped, positively-charged cavity surrounded by four loops for substrate binding and a catalytic center composed of conserved residues for specific Am nucleotide recognition and N6-methylation activity. Structural comparison of METTL4 with the mRNA m6A enzyme METTL3/METTL14 heterodimer and modeling analysis suggest a catalytic mechanism for N6-adenosine methylation by METTL4, which may be shared among MT-A70 family members.
β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the same GPCR in living cells
Authors: Haider Raphael S. , Matthees Edda S. F. , Drube Julia , Reichel Mona , Zabel Ulrike , Inoue Asuka , Chevigné Andy , Krasel Cornelius , Deupi Xavier , Hoffmann Carsten 
Published: September 2022

Abstractβ-arrestins mediate regulatory processes for over 800 different G protein-coupled receptors (GPCRs) by adopting specific conformations that result from the geometry of the GPCR–β-arrestin complex. However, whether β-arrestin1 and 2 respond differently for binding to the same GPCR is still unknown. Employing GRK knockout cells and β-arrestins lacking the finger-loop-region, we show that the two isoforms prefer to associate with the active parathyroid hormone 1 receptor (PTH1R) in different complex configurations (“hanging” and “core”). Furthermore, the utilisation of advanced NanoLuc/FlAsH-based biosensors reveals distinct conformational signatures of β-arrestin1 and 2 when bound to active PTH1R (P-R*). Moreover, we assess β-arrestin conformational changes that are induced specifically by proximal and distal C-terminal phosphorylation and in the absence of GPCR kinases (GRKs) (R*). Here, we show differences between conformational changes that are induced by P-R* or R* receptor states and further disclose the impact of site-specific GPCR phosphorylation on arrestin-coupling and function.
A self-complementary macrocycle by a dual interaction system
Authors: Sawanaka Yuta , Yamashina Masahiro , Ohtsu Hiroyoshi , Toyota Shinji 
Published: September 2022

AbstractSelf-complementary assembly is one of the most promising phenomena for the formation of discrete assemblies, e.g., proteins and capsids. However, self-complementary assembly based on multiple host-guest systems has been scarcely reported due to the difficulty in controlling each assembly. Herein, we report a dual interaction system in which the key assembly direction is well regulated by both π-π stacking and hydrogen bonding to construct a self-complementary macrocycle. Continuous host-guest behavior of anthracene-based molecular tweezers during crystallization leads to successful construction of a cyclic hexamer, which is reminiscent of Kekulé’s monkey model. Furthermore, the cyclic hexamer in a tight and triple-layered fashion shows hierarchical assembly into cuboctahedron and rhombohedral assemblies in the presence of trifluoroacetic acid. Our findings would be potentially one of metal-free strategies for constructing anthracene-based supramolecular assemblies with higher-order structure.
The role of gravitational body forces in the development of metamorphic core complexes
Authors: Bahadori Alireza , Holt William E. , Austermann Jacqueline , Campbell Lajhon , Rasbury E. Troy , Davis Daniel M. , Calvelage Christopher M. , Flesch Lucy M. 
Published: September 2022

AbstractWithin extreme continental extension areas, ductile middle crust is exhumed at the surface as metamorphic core complexes. Sophisticated quantitative models of extreme extension predicted upward transport of ductile middle-lower crust through time. Here we develop a general model for metamorphic core complexes formation and demonstrate that they result from the collapse of a mountain belt supported by a thickened crustal root. We show that gravitational body forces generated by topography and crustal root cause an upward flow pattern of the ductile lower-middle crust, facilitated by a detachment surface evolving into low-angle normal fault. This detachment surface acquires large amounts of finite strain, consistent with thick mylonite zones found in metamorphic core complexes. Isostatic rebound exposes the detachment in a domed upwarp, while the final Moho discontinuity across the extended region relaxes to a flat geometry. This work suggests that belts of metamorphic core complexes are a fossil signature of collapsed highlands.
Nocturnal plant respiration is under strong non-temperature control
Authors: Bruhn Dan , Newman Freya , Hancock Mathilda , Povlsen Peter , Slot Martijn , Sitch Stephen , Drake John , Weedon Graham P. , Clark Douglas B. , Pagter Majken , Ellis Richard J. , Tjoelker Mark G. , Andersen Kelly M. , Correa Zorayda Restrepo , McGuire Patrick C. , Mercado Lina M. 
Published: September 2022

AbstractMost biological rates depend on the rate of respiration. Temperature variation is typically considered the main driver of daily plant respiration rates, assuming a constant daily respiration rate at a set temperature. Here, we show empirical data from 31 species from temperate and tropical biomes to demonstrate that the rate of plant respiration at a constant temperature decreases monotonically with time through the night, on average by 25% after 8 h of darkness. Temperature controls less than half of the total nocturnal variation in respiration. A new universal formulation is developed to model and understand nocturnal plant respiration, combining the nocturnal decrease in the rate of plant respiration at constant temperature with the decrease in plant respiration according to the temperature sensitivity. Application of the new formulation shows a global reduction of 4.5 −6 % in plant respiration and an increase of 7-10% in net primary production for the present-day.