bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cellular and KSHV A-to-I RNA editome in primary effusion lymphoma and its role in the viral lifecycle
Authors: Rajendren Suba , Ye Xiang , Dunker William , Richardson Antiana , Karijolich John 
Published: March 2023

AbstractAdenosine-to-inosine RNA editing is a major contributor to transcriptome diversity in animals with far-reaching biological consequences. Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of several human malignancies including primary effusion lymphoma (PEL). The extent of RNA editing within the KSHV transcriptome is unclear as is its contribution to the viral lifecycle. Here, we leverage a combination of biochemical and genomic approaches to determine the RNA editing landscape in host- and KSHV transcriptomes during both latent and lytic replication in PEL. Analysis of RNA editomes reveals it is dynamic, with increased editing upon reactivation and the potential to deregulate pathways critical for latency and tumorigenesis. In addition, we identify conserved RNA editing events within a viral microRNA and discover their role in miRNA biogenesis as well as viral infection. Together, these results describe the editome of PEL cells as well as a critical role for A-to-I editing in the KSHV lifecycle.
Insights into the formation and evolution of extraterrestrial amino acids from the asteroid Ryugu
Authors: Potiszil Christian , Ota Tsutomu , Yamanaka Masahiro , Sakaguchi Chie , Kobayashi Katsura , Tanaka Ryoji , Kunihiro Tak , Kitagawa Hiroshi , Abe Masanao , Miyazaki Akiko , Nakato Aiko , Nakazawa Satoru , Nishimura Masahiro , Okada Tatsuaki , Saiki Takanao , Tanaka Satoshi , Terui Fuyuto , Tsuda Yuichi , Usui Tomohiro , Watanabe Sei-ichiro , Yada Toru , Yogata Kasumi , Yoshikawa Makoto , Nakamura Eizo 
Published: March 2023

AbstractAll life on Earth contains amino acids and carbonaceous chondrite meteorites have been suggested as their source at the origin of life on Earth. While many meteoritic amino acids are considered indigenous, deciphering the extent of terrestrial contamination remains an issue. The Ryugu asteroid fragments (JAXA Hayabusa2 mission), represent the most uncontaminated primitive extraterrestrial material available. Here, the concentrations of amino acids from two particles from different touchdown sites (TD1 and TD2) are reported. The concentrations show that N,N-dimethylglycine (DMG) is the most abundant amino acid in the TD1 particle, but below detection limit in the other. The TD1 particle mineral components indicate it experienced more aqueous alteration. Furthermore, the relationships between the amino acids and the geochemistry suggest that DMG formed on the Ryugu progenitor body during aqueous alteration. The findings highlight the importance of aqueous chemistry for defining the ultimate concentrations of amino acids in primitive extraterrestrial samples.
Spatial transcriptomics using multiplexed deterministic barcoding in tissue
Authors: Wirth Johannes , Huber Nina , Yin Kelvin , Brood Sophie , Chang Simon , Martinez-Jimenez Celia P. , Meier Matthias 
Published: March 2023

AbstractSpatially resolved transcriptomics of tissue sections enables advances in fundamental and applied biomedical research. Here, we present Multiplexed Deterministic Barcoding in Tissue (xDBiT) to acquire spatially resolved transcriptomes of nine tissue sections in parallel. New microfluidic chips were developed to spatially encode mRNAs over a total tissue area of 1.17 cm2 with a 50 µm resolution. Optimization of the biochemical protocol increased read and gene counts per spot by one order of magnitude compared to previous reports. Furthermore, the introduction of alignment markers allowed seamless registration of images and spatial transcriptomic spots. Together with technological advances, we provide an open-source computational pipeline to prepare raw sequencing data for downstream analysis. The functionality of xDBiT was demonstrated by acquiring 16 spatially resolved transcriptomic datasets from five different murine organs, including the cerebellum, liver, kidney, spleen, and heart. Factor analysis and deconvolution of spatial transcriptomes allowed for in-depth characterization of the murine kidney.
Multistability, intermittency, and hybrid transitions in social contagion models on hypergraphs
Authors: Ferraz de Arruda Guilherme , Petri Giovanni , Rodriguez Pablo Martin , Moreno Yamir 
Published: March 2023

AbstractAlthough ubiquitous, interactions in groups of individuals are not yet thoroughly studied. Frequently, single groups are modeled as critical-mass dynamics, which is a widespread concept used not only by academics but also by politicians and the media. However, less explored questions are how a collection of groups will behave and how their intersection might change the dynamics. Here, we formulate this process as binary-state dynamics on hypergraphs. We showed that our model has a rich behavior beyond discontinuous transitions. Notably, we have multistability and intermittency. We demonstrated that this phenomenology could be associated with community structures, where we might have multistability or intermittency by controlling the number or size of bridges between communities. Furthermore, we provided evidence that the observed transitions are hybrid. Our findings open new paths for research, ranging from physics, on the formal calculation of quantities of interest, to social sciences, where new experiments can be designed.
Heterologous SARS-CoV-2 spike protein booster elicits durable and broad antibody responses against the receptor-binding domain
Authors: Takano Tomohiro , Sato Takashi , Kotaki Ryutaro , Moriyama Saya , Fukushi Shuetsu , Shinoda Masahiro , Kabasawa Kiyomi , Shimada Nagashige , Kousaka Mio , Adachi Yu , Onodera Taishi , Terahara Kazutaka , Isogawa Masanori , Matsumura Takayuki , Shinkai Masaharu , Takahashi Yoshimasa 
Published: March 2023

AbstractThe immunogenicity of mRNA vaccines has not been well studied when compared to different vaccine modalities in the context of additional boosters. Here we show that longitudinal analysis reveals more sustained SARS-CoV-2 spike receptor-binding domain (RBD)-binding IgG titers with the breadth to antigenically distinct variants by the S-268019-b spike protein booster compared to the BNT162b2 mRNA homologous booster. The durability and breadth of RBD-angiotensin-converting enzyme 2 (ACE2) binding inhibitory antibodies are pronounced in the group without systemic adverse events (AEs) after the S-268019-b booster, leading to the elevated neutralizing activities against Omicron BA.1 and BA.5 variants in the stratified group. In contrast, BNT162b2 homologous booster elicited antibodies to spike N-terminal domain in proportion to the AE scores. High-dimensional immune profiling identifies early CD16+ natural killer cell dynamics with CCR3 upregulation, as one of the correlates for the distinct anti-RBD antibody responses by the S-268019-b booster. Our results illustrate the combinational effects of heterologous booster on the immune dynamics and the durability and breadth of recalled anti-RBD antibody responses against emerging virus variants.
AlphaFlow: autonomous discovery and optimization of multi-step chemistry using a self-driven fluidic lab guided by reinforcement learning
Authors: Volk Amanda A. , Epps Robert W. , Yonemoto Daniel T. , Masters Benjamin S. , Castellano Felix N. , Reyes Kristofer G. , Abolhasani Milad 
Published: March 2023

AbstractClosed-loop, autonomous experimentation enables accelerated and material-efficient exploration of large reaction spaces without the need for user intervention. However, autonomous exploration of advanced materials with complex, multi-step processes and data sparse environments remains a challenge. In this work, we present AlphaFlow, a self-driven fluidic lab capable of autonomous discovery of complex multi-step chemistries. AlphaFlow uses reinforcement learning integrated with a modular microdroplet reactor capable of performing reaction steps with variable sequence, phase separation, washing, and continuous in-situ spectral monitoring. To demonstrate the power of reinforcement learning toward high dimensionality multi-step chemistries, we use AlphaFlow to discover and optimize synthetic routes for shell-growth of core-shell semiconductor nanoparticles, inspired by colloidal atomic layer deposition (cALD). Without prior knowledge of conventional cALD parameters, AlphaFlow successfully identified and optimized a novel multi-step reaction route, with up to 40 parameters, that outperformed conventional sequences. Through this work, we demonstrate the capabilities of closed-loop, reinforcement learning-guided systems in exploring and solving challenges in multi-step nanoparticle syntheses, while relying solely on in-house generated data from a miniaturized microfluidic platform. Further application of AlphaFlow in multi-step chemistries beyond cALD can lead to accelerated fundamental knowledge generation as well as synthetic route discoveries and optimization.
In situ acid etching boosts mercury accommodation capacities of transition metal sulfides
Authors: Li Hailong , Zheng Jiaoqin , Zheng Wei , Zu Hongxiao , Chen Hongmei , Yang Jianping , Qu Wenqi , Leng Lijian , Feng Yong , Yang Zequn 
Published: March 2023

AbstractTransition Metal sulfides (TMSs) are effective sorbents for entrapment of highly polluting thiophiles such as elemental mercury (Hg0). However, the application of these sorbents for mercury removal is stymied by their low accommodation capacities. Among the transition metal sulfides, only CuS has demonstrated industrially relevant accommodation capacity. The rest of the transition metal sulfides have 100-fold lower capacities than CuS. In this work, we overcome these limitations and develop a simple and scalable process to enhance Hg0accommodation capacities of TMSs. We achieve this by introducing structural motifs in TMSs by in situ etching. We demonstrate that in situ acid etching produces TMSs with defective surface and pore structure. These structural motifs promote Hg0surface adsorption and diffusion across the entire TMSs architecture. The process is highly versatile and the in situ etched transition metal sulfides show over 100-fold enhancement in their Hg0accommodation capacities. The generality and the scalability of the process provides a framework to develop TMSs for a broad range of applications.
Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice
Authors: Ye Qian , Liu Yi , Zhang Guiji , Deng Haijun , Wang Xiaojun , Tuo Lin , Chen Chang , Pan Xuanming , Wu Kang , Fan Jiangao , Pan Qin , Wang Kai , Huang Ailong , Tang Ni 
Published: March 2023

AbstractMetabolic associated fatty liver disease (MAFLD) encompasses a broad spectrum of hepatic disorders, including steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis. We demonstrated that phosphoenolpyruvate carboxykinase 1 (PCK1) plays a central role in MAFLD progression. Male mice with liver Pck1 deficiency fed a normal diet displayed hepatic lipid disorder and liver injury, whereas fibrosis and inflammation were aggravated in mice fed a high-fat diet with drinking water containing fructose and glucose (HFCD-HF/G). Forced expression of hepatic PCK1 by adeno-associated virus ameliorated MAFLD in male mice. PCK1 deficiency stimulated lipogenic gene expression and lipid synthesis. Moreover, loss of hepatic PCK1 activated the RhoA/PI3K/AKT pathway by increasing intracellular GTP levels, increasing secretion of platelet-derived growth factor-AA (PDGF-AA), and promoting hepatic stellate cell activation. Treatment with RhoA and AKT inhibitors or gene silencing of RhoA or AKT1 alleviated MAFLD progression in vivo. Hepatic PCK1 deficiency may be important in hepatic steatosis and fibrosis development through paracrine secretion of PDGF-AA in male mice, highlighting a potential therapeutic strategy for MAFLD.
Mixed-valence molybdenum oxide as a recyclable sorbent for silver removal and recovery from wastewater
Authors: Shao Penghui , Chang Ziwen , Li Min , Lu Xiang , Jiang Wenli , Zhang Kai , Luo Xubiao , Yang Liming 
Published: March 2023

AbstractSilver ions in wastewater streams are a major pollutant and a threat to human health. Given the increasing demand and relative scarcity of silver, these streams could be a lucrative source to extract metallic silver. Wastewater is a complex mixture of many different metal salts, and developing recyclable sorbents with high specificity towards silver ions remains a major challenge. Here we report that molybdenum oxide (MoOx) adsorbent with mixed-valence (Mo(V) and Mo(VI)) demonstrates high selectivity (distribution coefficient of 6437.40 mL g−1) for Ag+ and an uptake capacity of 2605.91 mg g−1. Our experimental results and density functional theory calculations illustrate the mechanism behind Ag+ adsorption and reduction. Our results show that Mo(V) species reduce Ag+ to metallic Ag, which decreases the energy barrier for subsequent Ag+ reductions, accounting for the high uptake of Ag+ from wastewater. Due to its high selectivity, MoOx favorably adsorbs Ag+ even in the presence of interfering ions. High selective recovery of Ag+ from wastewater (recovery efficiency = 97.9%) further supports the practical applications of the sorbent. Finally, MoOx can be recycled following silver recovery while maintaining a recovery efficiency of 97.1% after five cycles. The method is expected to provide a viable strategy to recover silver from wastewater.
Executioner caspases restrict mitochondrial RNA-driven Type I IFN induction during chemotherapy-induced apoptosis
Authors: Killarney Shane T. , Washart Rachel , Soderquist Ryan S. , Hoj Jacob P. , Lebhar Jamie , Lin Kevin H. , Wood Kris C. 
Published: March 2023

AbstractDuring apoptosis, mitochondrial outer membrane permeabilization (MOMP) enables certain mitochondrial matrix macromolecules to escape into the cytosol. However, the fate of mitochondrial RNA (mtRNA) during apoptosis is unknown. Here, we demonstrate that MOMP results in the cytoplasmic release of mtRNA and that executioner caspases-3 and -7 (casp3/7) prevent cytoplasmic mtRNA from triggering inflammatory signaling. In the setting of genetic or pharmacological casp3/7 inhibition, apoptotic insults result in mtRNA activation of the MDA5/MAVS/IRF3 pathway to drive Type I interferon (IFN) signaling. This pathway is sufficient to activate tumor-intrinsic Type I IFN signaling in immunologically cold cancer models that lack an intact cGAS/STING signaling pathway, promote CD8+T-cell-dependent anti-tumor immunity, and overcome anti-PD1 refractoriness in vivo. Thus, a key function of casp3/7 is to inhibit inflammation caused by the cytoplasmic release of mtRNA, and pharmacological modulation of this pathway increases the immunogenicity of chemotherapy-induced apoptosis.
Litter accumulation and fire risks show direct and indirect climate-dependence at continental scale
Authors: Adams Mark A. , Neumann Mathias 
Published: March 2023

AbstractLitter decomposition / accumulation are rate limiting steps in soil formation, carbon sequestration, nutrient cycling and fire risk in temperate forests, highlighting the importance of robust predictive models at all geographic scales. Using a data set for the Australian continent, we show that among a range of models, most of the variance in litter mass over a 40-year time span can be accounted for by a parsimonious model with elapsed time, and indices of climate and litter quality, as independent drivers. Climate is an important driver of variation in both the species identity of dominant eucalypts and litter accumulation across the continent. Litter quality shows emergent properties of climate-dependence and contributes to explained variance. Nonetheless, elapsed time dominated explained variance in litter mass (up to 90%) at continental scale. Results provide guidance for future decomposition studies. Algorithms reported here can significantly improve accuracy and reliability of predictions of carbon and nutrient dynamics and fire risk.
High-performance vertical field-effect organic photovoltaics
Authors: Wu Xiaomin , Gao Changsong , Chen Qizhen , Yan Yujie , Zhang Guocheng , Guo Tailiang , Chen Huipeng 
Published: March 2023

AbstractLimited by the inherent energy loss (Eloss) in carrier transport process, the device efficiency of organic solar cells shows inferior to traditional inorganic photovoltaic devices. Generally, molecular design, morphology optimization and interfacial engineering are usually required to alleviate Eloss. Here, vertical field-effect organic photovoltaic (VFEOPV) by integrating an bulk-heterojunction (BHJ) organic photovoltaic (OPV) with vertical field effect transistor (VFET) is invented, in which VFET generates a large, uneven, internal electric field, eliminating the requirement for driving force to dissociate excitons and prevents non-radiative recombination in OPV. In this way, the performance of solar cell can be well controlled by the gate voltage of VFET and the Eloss of VFEOPVs based on J71: ITIC system is dramatically reduced below 0.2 eV, significantly improving power conversion efficiency (PCE) from 10% to 18% under gate voltage of 0.9 V, which only causes negligible additional power consumption (~10−4mJ/cm2). Besides, the device also exhibits multi-functionality including transistor and phototransistors with excellent photodector performance. This work provides a new and general strategy to improve the OPV performance which is compatible with present optimization methods, and can be applied to improve PCE of other types of solar cells such as Perovskite and inorganic solar cells.
Polyvinyl chloride-based dielectric elastomer with high permittivity and low viscoelasticity for actuation and sensing
Authors: Huang Jianjian , Zhang Xiaodie , Liu Ruixue , Ding Yonghui , Guo Dongjie 
Published: March 2023

AbstractDielectric elastomers (DEs) are widely used in soft actuation and sensing. Current DE actuators require high driving electrical fields because of their low permittivity. Most of DE actuators and sensors suffer from high viscoelastic effects, leading to high mechanical loss and large shifts of signals. This study demonstrates a valuable strategy to produce polyvinyl chloride (PVC)-based elastomers with high permittivity and low viscoelasticity. The introduction of cyanoethyl cellulose (CEC) into plasticized PVC gel (PVCg) not only confers a high dielectric permittivity (18.9@1 kHz) but also significantly mitigates their viscoelastic effects with a low mechanical loss (0.04@1 Hz). The CEC/PVCg actuators demonstrate higher actuation performances over the existing DE actuators under low electrical fields and show marginal displacement shifts (7.78%) compared to VHB 4910 (136.09%). The CEC/PVCg sensors display high sensitivity, fast response, and limited signal drifts, enabling their faithful monitoring of multiple human motions.
The evolution of antibiotic resistance is associated with collateral drug phenotypes in Mycobacterium tuberculosis
Authors: Waller Natalie J. E. , Cheung Chen-Yi , Cook Gregory M. , McNeil Matthew B. 
Published: March 2023

AbstractThe increasing incidence of drug resistance in Mycobacterium tuberculosis has diminished the efficacy of almost all available antibiotics, complicating efforts to combat the spread of this global health burden. Alongside the development of new drugs, optimised drug combinations are needed to improve treatment success and prevent the further spread of antibiotic resistance. Typically, antibiotic resistance leads to reduced sensitivity, yet in some cases the evolution of drug resistance can lead to enhanced sensitivity to unrelated drugs. This phenomenon of collateral sensitivity is largely unexplored in M. tuberculosis but has the potential to identify alternative therapeutic strategies to combat drug-resistant strains that are unresponsive to current treatments. Here, by using drug susceptibility profiling, genomics and evolutionary studies we provide evidence for the existence of collateral drug sensitivities in an isogenic collection M. tuberculosis drug-resistant strains. Furthermore, in proof-of-concept studies, we demonstrate how collateral drug phenotypes can be exploited to select against and prevent the emergence of drug-resistant strains. This study highlights that the evolution of drug resistance in M. tuberculosis leads to collateral drug responses that can be exploited to design improved drug regimens.
Structural insight into the intraflagellar transport complex IFT-A and its assembly in the anterograde IFT train
Authors: Ma Yuanyuan , He Jun , Li Shaobai , Yao Deqiang , Huang Chenhui , Wu Jian , Lei Ming 
Published: March 2023

AbstractIntraflagellar transport (IFT) trains, the polymers composed of two multi-subunit complexes, IFT-A and IFT-B, carry out bidirectional intracellular transport in cilia, vital for cilia biogenesis and signaling. IFT-A plays crucial roles in the ciliary import of membrane proteins and the retrograde cargo trafficking. However, the molecular architecture of IFT-A and the assembly mechanism of the IFT-A into the IFT trains in vivo remains elusive. Here, we report the cryo-electron microscopic structures of the IFT-A complex from protozoa Tetrahymena thermophila. We find that IFT-A complexes present two distinct, elongated and folded states. Remarkably, comparison with the in situ cryo-electron tomography structure of the anterograde IFT train unveils a series of adjustments of the flexible arms in apo IFT-A when incorporated into the anterograde train. Our results provide an atomic-resolution model for the IFT-A complex and valuable insights into the assembly mechanism of anterograde IFT trains.
Synthetic lethality of drug-induced polyploidy and BCL-2 inhibition in lymphoma
Authors: Portelinha Ana , da Silva Ferreira Mariana , Erazo Tatiana , Jiang Man , Asgari Zahra , de Stanchina Elisa , Younes Anas , Wendel Hans-Guido 
Published: March 2023

AbstractSpontaneous whole genome duplication and the adaptive mutations that disrupt genome integrity checkpoints are infrequent events in B cell lymphomas. This suggests that lymphomas might be vulnerable to therapeutics that acutely trigger genomic instability and polyploidy. Here, we report a therapeutic combination of inhibitors of the Polo-like kinase 4 and BCL-2 that trigger genomic instability and cell death in aggressive lymphomas. The synthetic lethality is selective for tumor cells and spares vital organs. Mechanistically, inhibitors of Polo-like kinase 4 impair centrosome duplication and cause genomic instability. The elimination of polyploid cells largely depends on the pro-apoptotic BAX protein. Consequently, the combination of drugs that induce polyploidy with the BCL-2 inhibitor Venetoclax is highly synergistic and safe against xenograft and PDX models. We show that B cell lymphomas are ill-equipped for acute, therapy-induced polyploidy and that BCL-2 inhibition further enhances the removal of polyploid lymphoma cells.