bluuebunny/crossref_metadata_2025_split huggingface dataset:
Negative regulation of pro-apoptotic AMPK/JNK pathway by itaconate in mice with fulminant liver injury
Authors: Fan Kerui , Chen Kun , Zan Xinyan , Zhi Ying , Zhang Xue , Zhang Xinyue , Qiu Jinghuan , Liu Gang , Li Longjiang , Tang Li , Hu Kai , Wan Jingyuan , Gong Xianqiong , Yang Yongqiang , Zhang Li 
Published: July 2023

AbstractAccumulating evidence indicates that metabolic responses are deeply integrated into signal transduction, which provides novel opportunities for the metabolic control of various disorders. Recent studies suggest that itaconate, a highly concerned bioactive metabolite catalyzed by immune responsive gene 1 (IRG1), is profoundly involved in the regulation of apoptosis, but the underlying mechanisms have not been fully understood. In the present study, the molecular mechanisms responsible for the apoptosis-modulatory activities of IRG1/itaconate have been investigated in mice with lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced apoptotic liver injury. The results indicated that LPS/D-Gal exposure upregulated the level of IRG1 and itaconate. Deletion of IRG1 resulted in exacerbated hepatocytes apoptosis and liver injury. The phospho-antibody microarray analysis and immunoblot analysis indicated that IRG1 deletion enhanced the activation of AMP-activated protein kinase (AMPK)/c-jun-N-terminal kinase (JNK) pathway in LPS/D-Gal exposed mice. Mechanistically, IRG1 deficiency impaired the anti-oxidative nuclear factor erythroid-2 related factor 2 (Nrf2) signaling and then enhanced the activation of the redox-sensitive AMPK/JNK pathway that promotes hepatocytes apoptosis. Importantly, post-insult supplementation with 4-octyl itaconate (4-OI), a cell-permeable derivate of itaconate, resulted in beneficial outcomes in fulminant liver injury. Therefore, IRG1/itaconate might function as a negative regulator that controls AMPK-induced hepatocyte apoptosis in LPS/D-Gal-induced fulminant liver injury.
Structural insights into ligand recognition and subtype selectivity of the human melanocortin-3 and melanocortin-5 receptors
Authors: Feng Wenbo , Zhou Qingtong , Chen Xianyue , Dai Antao , Cai Xiaoqing , Liu Xiao , Zhao Fenghui , Chen Yan , Ye Chenyu , Xu Yingna , Cong Zhaotong , Li Hao , Lin Shi , Yang Dehua , Wang Ming-Wei 
Published: July 2023

AbstractMembers of the melanocortin receptor (MCR) family that recognize different melanocortin peptides mediate a broad spectrum of cellular processes including energy homeostasis, inflammation and skin pigmentation through five MCR subtypes (MC1R–MC5R). The structural basis of subtype selectivity of the endogenous agonist γ-MSH and non-selectivity of agonist α-MSH remains elusive, as the two agonists are highly similar with a conserved HFRW motif. Here, we report three cryo-electron microscopy structures of MC3R–Gs in complex with γ-MSH and MC5R–Gs in the presence of α-MSH or a potent synthetic agonist PG-901. The structures reveal that α-MSH and γ-MSH adopt a “U-shape” conformation, penetrate into the wide-open orthosteric pocket and form massive common contacts with MCRs via the HFRW motif. The C-terminus of γ-MSH occupies an MC3R-specific complementary binding groove likely conferring subtype selectivity, whereas that of α-MSH distances itself from the receptor with neglectable contacts. PG-901 achieves the same potency as α-MSH with a shorter length by rebalancing the recognition site and mimicking the intra-peptide salt bridge in α-MSH by cyclization. Solid density confirmed the calcium ion binding in MC3R and MC5R, and the distinct modulation effects of divalent ions were demonstrated. Our results provide insights into ligand recognition and subtype selectivity among MCRs, and expand the knowledge of signal transduction among MCR family members.
A multifunctional soft robotic shape display with high-speed actuation, sensing, and control
Authors: Johnson B. K. , Naris M. , Sundaram V. , Volchko A. , Ly K. , Mitchell S. K. , Acome E. , Kellaris N. , Keplinger C. , Correll N. , Humbert J. S. , Rentschler M. E. 
Published: July 2023

AbstractShape displays which actively manipulate surface geometry are an expanding robotics domain with applications to haptics, manufacturing, aerodynamics, and more. However, existing displays often lack high-fidelity shape morphing, high-speed deformation, and embedded state sensing, limiting their potential uses. Here, we demonstrate a multifunctional soft shape display driven by a 10 × 10 array of scalable cellular units which combine high-speed electrohydraulic soft actuation, magnetic-based sensing, and control circuitry. We report high-performance reversible shape morphing up to 50 Hz, sensing of surface deformations with 0.1 mm sensitivity and external forces with 50 mN sensitivity in each cell, which we demonstrate across a multitude of applications including user interaction, image display, sensing of object mass, and dynamic manipulation of solids and liquids. This work showcases the rich multifunctionality and high-performance capabilities that arise from tightly-integrating large numbers of electrohydraulic actuators, soft sensors, and controllers at a previously undemonstrated scale in soft robotics.
Three-dimensional molecular architecture of mouse organogenesis
Authors: Qu Fangfang , Li Wenjia , Xu Jian , Zhang Ruifang , Ke Jincan , Ren Xiaodie , Meng Xiaogao , Qin Lexin , Zhang Jingna , Lu Fangru , Zhou Xin , Luo Xi , Zhang Zhen , Wang Minhan , Wu Guangming , Pei Duanqing , Chen Jiekai , Cui Guizhong , Suo Shengbao , Peng Guangdun 
Published: July 2023

AbstractMammalian embryos exhibit sophisticated cellular patterning that is intricately orchestrated at both molecular and cellular level. It has recently become apparent that cells within the animal body display significant heterogeneity, both in terms of their cellular properties and spatial distributions. However, current spatial transcriptomic profiling either lacks three-dimensional representation or is limited in its ability to capture the complexity of embryonic tissues and organs. Here, we present a spatial transcriptomic atlas of all major organs at embryonic day 13.5 in the mouse embryo, and provide a three-dimensional rendering of molecular regulation for embryonic patterning with stacked sections. By integrating the spatial atlas with corresponding single-cell transcriptomic data, we offer a detailed molecular annotation of the dynamic nature of organ development, spatial cellular interactions, embryonic axes, and divergence of cell fates that underlie mammalian development, which would pave the way for precise organ engineering and stem cell-based regenerative medicine.
A Phytophthora receptor-like kinase regulates oospore development and can activate pattern-triggered plant immunity
Authors: Pei Yong , Ji Peiyun , Si Jierui , Zhao Hanqing , Zhang Sicong , Xu Ruofei , Qiao Huijun , Duan Weiwei , Shen Danyu , Yin Zhiyuan , Dou Daolong 
Published: July 2023

AbstractPlant cell-surface leucine-rich repeat receptor-like kinases (LRR-RLKs) and receptor-like proteins (LRR-RLPs) form dynamic complexes to receive a variety of extracellular signals. LRR-RLKs are also widespread in oomycete pathogens, whereas it remains enigmatic whether plant and oomycete LRR-RLKs could mediate cell-to-cell communications between pathogen and host. Here, we report that an LRR-RLK from the soybean root and stem rot pathogen Phytophthora sojae, PsRLK6, can activate typical pattern-triggered immunity in host soybean and nonhost tomato and Nicotiana benthamiana plants. PsRLK6 homologs are conserved in oomycetes and also exhibit immunity-inducing activity. A small region (LRR5-6) in the extracellular domain of PsRLK6 is sufficient to activate BAK1- and SOBIR1-dependent immune responses, suggesting that PsRLK6 is likely recognized by a plant LRR-RLP. Moreover, PsRLK6 is shown to be up-regulated during oospore maturation and essential for the oospore development of P. sojae. Our data provide a novel type of microbe-associated molecular pattern that functions in the sexual reproduction of oomycete, and a scenario in which a pathogen LRR-RLK could be sensed by a plant LRR-RLP to mount plant immunity.
A photochemical method to evidence directional molecular motions
Authors: Regen-Pregizer Benjamin Lukas , Ozcelik Ani , Mayer Peter , Hampel Frank , Dube Henry 
Published: July 2023

AbstractLight driven synthetic molecular motors represent crucial building blocks for advanced molecular machines and their applications. A standing challenge is the development of very fast molecular motors able to perform rotations with kHz, MHz or even faster frequencies. Central to this challenge is the direct experimental evidence of directionality because analytical methods able to follow very fast motions rarely deliver precise geometrical insights. Here, a general photochemical method for elucidation of directional motions is presented. In a macrocyclization approach the molecular motor rotations are restricted and forced to proceed in two separate ~180° rotation-photoequilibria. Therefore, all four possible photoinduced rotation steps (clockwise and counterclockwise directions) can be quantified. Comparison of the corresponding quantum yields to the unrestricted motor delivers direct evidence for unidirectionality. This method can be used for any ultrafast molecular motor even in cases where no high energy intermediates are present during the rotation cycle.
Lysophosphatidylserine induces necrosis in pressure overloaded male mouse hearts via G protein coupled receptor 34
Authors: Sugihara Ryuta , Taneike Manabu , Murakawa Tomokazu , Tamai Takahito , Ueda Hiromichi , Kitazume-Taneike Rika , Oka Takafumi , Akazawa Yasuhiro , Nishida Hiroki , Mine Kentaro , Hioki Ayana , Omi Jumpei , Omiya Shigemiki , Aoki Junken , Ikeda Kazutaka , Nishida Kazuhiko , Arita Makoto , Yamaguchi Osamu , Sakata Yasushi , Otsu Kinya 
Published: July 2023

AbstractHeart failure is a leading cause of mortality in developed countries. Cell death is a key player in the development of heart failure. Calcium-independent phospholipase A2β (iPLA2β) produces lipid mediators by catalyzing lipids and induces nuclear shrinkage in caspase-independent cell death. Here, we show that lysophosphatidylserine generated by iPLA2β induces necrotic cardiomyocyte death, as well as contractile dysfunction mediated through its receptor, G protein-coupled receptor 34 (GPR34). Cardiomyocyte-specific iPLA2β-deficient male mice were subjected to pressure overload. While control mice showed left ventricular systolic dysfunction with necrotic cardiomyocyte death, iPLA2β-deficient mice preserved cardiac function. Lipidomic analysis revealed a reduction of 18:0 lysophosphatidylserine in iPLA2β-deficient hearts. Knockdown of Gpr34 attenuated 18:0 lysophosphatidylserine-induced necrosis in neonatal male rat cardiomyocytes, while the ablation of Gpr34 in male mice reduced the development of pressure overload-induced cardiac remodeling. Thus, the iPLA2β—lysophosphatidylserine—GPR34—necrosis signaling axis plays a detrimental role in the heart in response to pressure overload.
Late Cambrian geomagnetic instability after the onset of inner core nucleation
Authors: Li Yong-Xiang , Tarduno John A. , Jiao Wenjun , Liu Xinyu , Peng Shanchi , Xu Shihua , Yang Aihua , Yang Zhenyu 
Published: July 2023

AbstractThe Ediacaran Period marks a pivotal time in geodynamo evolution when the geomagnetic field is thought to approach the weak state where kinetic energy exceeds magnetic energy, as manifested by an extremely high frequency of polarity reversals, high secular variation, and an ultralow dipole field strength. However, how the geodynamo transitioned from this state into one with more stable field behavior is unknown. Here, we address this issue through a high-resolution magnetostratigraphic investigation of the ~494.5 million-year-old Jiangshanian Global Standard Stratotype and Point (GSSP) section in South China. Our paleomagnetic results document zones with rapid reversals, stable polarity and a ~80 thousand-year-long interval without a geocentric axial dipole field. From these changes, we suggest that for most of the Cambrian, the solid inner core had not yet grown to a size sufficiently large to stabilize the geodynamo. This unusual field behavior can explain paleomagnetic data used to define paradoxical true polar wander, supporting instead the rotational stability of the solid Earth during the great radiation of life in the Cambrian.
Ionomer-free and recyclable porous-transport electrode for high-performing proton-exchange-membrane water electrolysis
Authors: Lee Jason K. , Anderson Grace , Tricker Andrew W. , Babbe Finn , Madan Arya , Cullen David A. , Arregui-Mena José’ D. , Danilovic Nemanja , Mukundan Rangachary , Weber Adam Z. , Peng Xiong 
Published: July 2023

AbstractClean hydrogen production requires large-scale deployment of water-electrolysis technologies, particularly proton-exchange-membrane water electrolyzers (PEMWEs). However, as iridium-based electrocatalysts remain the only practical option for PEMWEs, their low abundance will become a bottleneck for a sustainable hydrogen economy. Herein, we propose high-performing and durable ionomer-free porous transport electrodes (PTEs) with facile recycling features enabling Ir thrifting and reclamation. The ionomer-free porous transport electrodes offer a practical pathway to investigate the role of ionomer in the catalyst layer and, from microelectrode measurements, point to an ionomer poisoning effect for the oxygen evolution reaction. The ionomer-free porous transport electrodes demonstrate a voltage reduction of > 600 mV compared to conventional ionomer-coated porous transport electrodes at 1.8 A cm−2 and <0.1 mgIr cm−2, and a voltage degradation of 29 mV at average rate of 0.58 mV per 1000-cycles after 50k cycles of accelerated-stress tests at 4 A cm−2. Moreover, the ionomer-free feature enables facile recycling of multiple components of PEMWEs, which is critical to a circular clean hydrogen economy.
Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton
Authors: Doolittle Madison L. , Saul Dominik , Kaur Japneet , Rowsey Jennifer L. , Vos Stephanie J. , Pavelko Kevin D. , Farr Joshua N. , Monroe David G. , Khosla Sundeep 
Published: July 2023

AbstractSenescence drives organismal aging, yet the deep characterization of senescent cells in vivo remains incomplete. Here, we apply mass cytometry by time-of-flight using carefully validated antibodies to analyze senescent cells at single-cell resolution. We use multiple criteria to identify senescent mesenchymal cells that are growth-arrested and resistant to apoptosis. These p16 + Ki67-BCL-2+ cells are highly enriched for senescence-associated secretory phenotype and DNA damage markers, are strongly associated with age, and their percentages are increased in late osteoblasts/osteocytes and CD24high osteolineage cells. Moreover, both late osteoblasts/osteocytes and CD24high osteolineage cells are robustly cleared by genetic and pharmacologic senolytic therapies in aged mice. Following isolation, CD24+ skeletal cells exhibit growth arrest, senescence-associated β-galactosidase positivity, and impaired osteogenesis in vitro. These studies thus provide an approach using multiplexed protein profiling to define senescent mesenchymal cells in vivo and identify specific skeletal cell populations cleared by senolytics.
Enhanced clay formation key in sustaining the Middle Eocene Climatic Optimum
Authors: Krause Alexander J. , Sluijs Appy , van der Ploeg Robin , Lenton Timothy M. , Pogge von Strandmann Philip A. E. 
Published: July 2023

AbstractThe Middle Eocene Climatic Optimum (around 40 million years ago) was a roughly 400,000-year-long global warming phase associated with an increase in atmospheric CO2 concentrations and deep-ocean acidification that interrupted the Eocene’s long-term cooling trend. The unusually long duration, compared with early Eocene global warming phases, is puzzling as temperature-dependent silicate weathering should have provided a negative feedback, drawing down CO2 over this timescale. Here we investigate silicate weathering during this climate warming event by measuring lithium isotope ratios (reported as δ7Li), which are a tracer for silicate weathering processes, from a suite of open-ocean carbonate-rich sediments. We find a positive δ7Li excursion—the only one identified for a warming event so far —of ~3‰. Box model simulations support this signal to reflect a global shift from congruent weathering, with secondary mineral dissolution, to incongruent weathering, with secondary mineral formation. We surmise that, before the climatic optimum, there was considerable soil shielding of the continents. An increase in continental volcanism initiated the warming event, but it was sustained by an increase in clay formation, which sequestered carbonate-forming cations, short-circuiting the carbonate–silicate cycle. Clay mineral dynamics may play an important role in the carbon cycle for climatic events occurring over intermediate (i.e., 100,000 year) timeframes.
Himalayan valley-floor widths controlled by tectonically driven exhumation
Authors: Clubb Fiona J. , Mudd Simon M. , Schildgen Taylor F. , van der Beek Peter A. , Devrani Rahul , Sinclair Hugh D. 
Published: July 2023

AbstractHimalayan rivers transport around a gigaton of sediment annually to ocean basins. Mountain valleys are an important component of this routing system: storage in these valleys acts to buffer climatic and tectonic signals recorded by downstream sedimentary systems. Despite a critical need to understand the spatial distribution, volume and longevity of these valley fills, controls on valley location and geometry are unknown, and estimates of sediment volumes are based on assumptions of valley-widening processes. Here we extract over 1.5 million valley-floor width measurements across the Himalaya to determine the dominant controls on valley-floor morphology and to assess sediment-storage processes. Using random forest regression, we show that channel steepness, a proxy for rock uplift, is a first-order control on valley-floor width. On the basis of a dataset of 1,148 exhumation rates, we find that valley-floor width decreases as exhumation rate increases. Our results suggest that valley-floor width is controlled by long-term tectonically driven exhumation rather than by water discharge or bedrock erodibility and that valley widening predominantly results from sediment deposition along low-gradient valley floors rather than lateral bedrock erosion.
SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response
Authors: Bland Philip , Saville Harry , Wai Patty T. , Curnow Lucinda , Muirhead Gareth , Nieminuszczy Jadwiga , Ravindran Nivedita , John Marie Beatrix , Hedayat Somaieh , Barker Holly E. , Wright James , Yu Lu , Mavrommati Ioanna , Read Abigail , Peck Barrie , Allen Mark , Gazinska Patrycja , Pemberton Helen N. , Gulati Aditi , Nash Sarah , Noor Farzana , Guppy Naomi , Roxanis Ioannis , Pratt Guy , Oldreive Ceri , Stankovic Tatjana , Barlow Samantha , Kalirai Helen , Coupland Sarah E. , Broderick Ronan , Alsafadi Samar , Houy Alexandre , Stern Marc-Henri , Pettit Stephen , Choudhary Jyoti S. , Haider Syed , Niedzwiedz Wojciech , Lord Christopher J. , Natrajan Rachael 
Published: July 2023

AbstractSF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that SF3B1 mutant (SF3B1MUT) cells are selectively sensitive to poly (ADP-ribose) polymerase inhibitors (PARPi), independent of hotspot mutation and tumor site. SF3B1MUT cells display a defective response to PARPi-induced replication stress that occurs via downregulation of the cyclin-dependent kinase 2 interacting protein (CINP), leading to increased replication fork origin firing and loss of phosphorylated CHK1 (pCHK1; S317) induction. This results in subsequent failure to resolve DNA replication intermediates and G2/M cell cycle arrest. These defects are rescued through CINP overexpression, or further targeted by a combination of ataxia-telangiectasia mutated and PARP inhibition. In vivo, PARPi produce profound antitumor effects in multiple SF3B1MUT cancer models and eliminate distant metastases. These data provide the rationale for testing the clinical efficacy of PARPi in a biomarker-driven, homologous recombination proficient, patient population.
Entanglement propagation and dynamics in non-additive quantum systems
Authors: Giachetti Guido , Defenu Nicolò 
Published: July 2023

AbstractThe prominent collective character of long-range interacting quantum systems makes them promising candidates for quantum technological applications. Yet, lack of additivity overthrows the traditional picture for entanglement scaling and transport, due to the breakdown of the common mechanism based on excitations propagation and confinement. Here, we describe the dynamics of the entanglement entropy in many-body quantum systems with a diverging contribution to the internal energy from the long-range two body potential. While in the strict thermodynamic limit entanglement dynamics is shown to be suppressed, a rich mosaic of novel scaling regimes is observed at intermediate system sizes, due to the possibility to trigger multiple resonant modes in the global dynamics. Quantitative predictions on the shape and timescales of entanglement propagation are made, paving the way to the observation of these phases in current quantum simulators. This picture is connected and contrasted with the case of local many body systems subject to Floquet driving.
A neural encoder for earthquake rate forecasting
Authors: Zlydenko Oleg , Elidan Gal , Hassidim Avinatan , Kukliansky Doron , Matias Yossi , Meade Brendan , Molchanov Alexandra , Nevo Sella , Bar-Sinai Yohai 
Published: July 2023

AbstractForecasting the timing of earthquakes is a long-standing challenge. Moreover, it is still debated how to formulate this problem in a useful manner, or to compare the predictive power of different models. Here, we develop a versatile neural encoder of earthquake catalogs, and apply it to the fundamental problem of earthquake rate prediction, in the spatio-temporal point process framework. The epidemic type aftershock sequence model (ETAS) effectively learns a small number of parameters to constrain the assumed functional forms for the space and time correlations of earthquake sequences (e.g., Omori-Utsu law). Here we introduce learned spatial and temporal embeddings for point process earthquake forecasting models that capture complex correlation structures. We demonstrate the generality of this neural representation as compared with ETAS model using train-test data splits and how it enables the incorporation additional geophysical information. In rate prediction tasks, the generalized model shows$$>4\%$$>4%improvement in information gain per earthquake and the simultaneous learning of anisotropic spatial structures analogous to fault traces. The trained network can be also used to perform short-term prediction tasks, showing similar improvement while providing a 1000-fold reduction in run-time.