bluuebunny/crossref_metadata_2025_split huggingface dataset:
Universal machine learning aided synthesis approach of two-dimensional perovskites in a typical laboratory
Authors: Wu Yilei , Wang Chang-Feng , Ju Ming-Gang , Jia Qiangqiang , Zhou Qionghua , Lu Shuaihua , Gao Xinying , Zhang Yi , Wang Jinlan 
Published: January 2024

AbstractThe past decade has witnessed the significant efforts in novel material discovery in the use of data-driven techniques, in particular, machine learning (ML). However, since it needs to consider the precursors, experimental conditions, and availability of reactants, material synthesis is generally much more complex than property and structure prediction, and very few computational predictions are experimentally realized. To solve these challenges, a universal framework that integrates high-throughput experiments, a priori knowledge of chemistry, and ML techniques such as subgroup discovery and support vector machine is proposed to guide the experimental synthesis of materials, which is capable of disclosing structure-property relationship hidden in high-throughput experiments and rapidly screening out materials with high synthesis feasibility from vast chemical space. Through application of our approach to challenging and consequential synthesis problem of 2D silver/bismuth organic-inorganic hybrid perovskites, we have increased the success rate of the synthesis feasibility by a factor of four relative to traditional approaches. This study provides a practical route for solving multidimensional chemical acceleration problems with small dataset from typical laboratory with limited experimental resources available.
T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors
Authors: Middelburg Jim , Sluijter Marjolein , Schaap Gaby , Göynük Büşra , Lloyd Katy , Ovcinnikovs Vitalijs , Zom Gijs G. , Marijnissen Renoud J. , Groeneveldt Christianne , Griffioen Lisa , Sandker Gerwin G. W. , Heskamp Sandra , van der Burg Sjoerd H. , Arakelian Tsolere , Ossendorp Ferry , Arens Ramon , Schuurman Janine , Kemper Kristel , van Hall Thorbald 
Published: January 2024

AbstractCD3 bispecific antibody (CD3 bsAb) therapy is clinically approved for refractory hematological malignancies, but responses in solid tumors have been limited so far. One of the main hurdles in solid tumors is the lack of sufficient T-cell infiltrate. Here, we show that pre-treatment vaccination, even when composed of tumor-unrelated antigens, induces CXCR3-mediated T-cell influx in immunologically ‘cold’ tumor models in male mice. In the absence of CD3 bsAb, the infiltrate is confined to the tumor invasive margin, whereas subsequent CD3 bsAb administration induces infiltration of activated effector CD8 T cells into the tumor cell nests. This combination therapy installs a broadly inflamed Th1-type tumor microenvironment, resulting in effective tumor eradication. Multiple vaccination formulations, including synthetic long peptides and viruses, empower CD3 bsAb therapy. Our results imply that eliciting tumor infiltration with vaccine-induced tumor-(un)related T cells can greatly improve the efficacy of CD3 bsAbs in solid tumors.
More than 17,000 tree species are at risk from rapid global change
Authors: Boonman Coline C. F. , Serra-Diaz Josep M. , Hoeks Selwyn , Guo Wen-Yong , Enquist Brian J. , Maitner Brian , Malhi Yadvinder , Merow Cory , Buitenwerf Robert , Svenning Jens-Christian 
Published: January 2024

AbstractTrees are pivotal to global biodiversity and nature’s contributions to people, yet accelerating global changes threaten global tree diversity, making accurate species extinction risk assessments necessary. To identify species that require expert-based re-evaluation, we assess exposure to change in six anthropogenic threats over the last two decades for 32,090 tree species. We estimated that over half (54.2%) of the assessed species have been exposed to increasing threats. Only 8.7% of these species are considered threatened by the IUCN Red List, whereas they include more than half of the Data Deficient species (57.8%). These findings suggest a substantial underestimation of threats and associated extinction risk for tree species in current assessments. We also map hotspots of tree species exposed to rapidly changing threats around the world. Our data-driven approach can strengthen the efforts going into expert-based IUCN Red List assessments by facilitating prioritization among species for re-evaluation, allowing for more efficient conservation efforts.
Mapping causal links between prefrontal cortical regions and
intra-individual behavioral variability
Authors: Alizadeh Mansouri Farshad , Buckley Mark J. , Tanaka Keiji 
Published: January 2024

AbstractIntra-individual behavioral variability is significantly heightened by
aging or neuropsychological disorders, however it is unknown which brain regions are
causally linked to such variabilities. We examine response time (RT) variability in
21 macaque monkeys performing a rule-guided decision-making task. In monkeys with
selective-bilateral lesions in the anterior cingulate cortex (ACC) or in the
dorsolateral prefrontal cortex, cognitive flexibility is impaired, but the RT
variability is significantly diminished. Bilateral lesions within the frontopolar
cortex or within the mid-dorsolateral prefrontal cortex, has no significant effect
on cognitive flexibility or RT variability. In monkeys with lesions in the posterior
cingulate cortex, the RT variability significantly increases without any deficit in
cognitive flexibility. The effect of lesions in the orbitofrontal cortex (OFC) is
unique in that it leads to deficits in cognitive flexibility and a significant
increase in RT variability. Our findings indicate remarkable dissociations in
contribution of frontal cortical regions to behavioral variability. They suggest
that the altered variability in OFC-lesioned monkeys is related to deficits in
assessing and accumulating evidence to inform a rule-guided decision, whereas in
ACC-lesioned monkeys it results from a non-adaptive decrease in decision threshold
and consequently immature impulsive responses.
Dopamine release in human associative striatum during reversal learning
Authors: Grill Filip , Guitart-Masip Marc , Johansson Jarkko , Stiernman Lars , Axelsson Jan , Nyberg Lars , Rieckmann Anna 
Published: January 2024

AbstractThe dopaminergic system is firmly implicated in reversal learning but human measurements of dopamine release as a correlate of reversal learning success are lacking. Dopamine release and hemodynamic brain activity in response to unexpected changes in action-outcome probabilities are here explored using simultaneous dynamic [11C]Raclopride PET-fMRI and computational modelling of behavior. When participants encounter reversed reward probabilities during a card guessing game, dopamine release is observed in associative striatum. Individual differences in absolute reward prediction error and sensitivity to errors are associated with peak dopamine receptor occupancy. The fMRI response to perseverance errors at the onset of a reversal spatially overlap with the site of dopamine release. Trial-by-trial fMRI correlates of absolute prediction errors show a response in striatum and association cortices, closely overlapping with the location of dopamine release, and separable from a valence signal in ventral striatum. The results converge to implicate striatal dopamine release in associative striatum as a central component of reversal learning, possibly signifying the need for increased cognitive control when new stimuli-responses should be learned.
Optogenetic spatial patterning of cooperation in yeast populations
Authors: Le Bec Matthias , Pouzet Sylvain , Cordier Céline , Barral Simon , Scolari Vittore , Sorre Benoit , Banderas Alvaro , Hersen Pascal 
Published: January 2024

AbstractMicrobial communities are shaped by complex metabolic interactions such as cooperation and competition for resources. Methods to control such interactions could lead to major advances in our ability to better engineer microbial consortia for synthetic biology applications. Here, we use optogenetics to control SUC2 invertase production in yeast, thereby shaping spatial assortment of cooperator and cheater cells. Yeast cells behave as cooperators (i.e., transform sucrose into hexose, a public good) upon blue light illumination or cheaters (i.e., consume hexose produced by cooperators to grow) in the dark. We show that cooperators benefit best from the hexoses they produce when their domain size is constrained between two cut-off length-scales. From an engineering point of view, the system behaves as a bandpass filter. The lower limit is the trace of cheaters’ competition for hexoses, while the upper limit is defined by cooperators’ competition for sucrose. Cooperation mostly occurs at the frontiers with cheater cells, which not only compete for hexoses but also cooperate passively by letting sucrose reach cooperators. We anticipate that this optogenetic method could be applied to shape metabolic interactions in a variety of microbial ecosystems.
Surplus fatty acid synthesis increases oxidative stress in adipocytes and induces lipodystrophy
Authors: Weng Li , Tang Wen-Shuai , Wang Xu , Gong Yingyun , Liu Changqin , Hong Ni-Na , Tao Ying , Li Kuang-Zheng , Liu Shu-Ning , Jiang Wanzi , Li Ying , Yao Ke , Chen Li , Huang He , Zhao Yu-Zheng , Hu Ze-Ping , Lu Youli , Ye Haobin , Du Xingrong , Zhou Hongwen , Li Peng , Zhao Tong-Jin 
Published: January 2024

AbstractAdipocytes are the primary sites for fatty acid storage, but the synthesis rate of fatty acids is very low. The physiological significance of this phenomenon remains unclear. Here, we show that surplus fatty acid synthesis in adipocytes induces necroptosis and lipodystrophy. Transcriptional activation of FASN elevates fatty acid synthesis, but decreases NADPH level and increases ROS production, which ultimately leads to adipocyte necroptosis. We identify MED20, a subunit of the Mediator complex, as a negative regulator of FASN transcription. Adipocyte-specific male Med20 knockout mice progressively develop lipodystrophy, which is reversed by scavenging ROS. Further, in a murine model of HIV-associated lipodystrophy and a human patient with acquired lipodystrophy, ROS neutralization significantly improves metabolic disorders, indicating a causal role of ROS in disease onset. Our study well explains the low fatty acid synthesis rate in adipocytes, and sheds light on the management of acquired lipodystrophy.
Sub-Doppler optical-optical double-resonance spectroscopy using
a cavity-enhanced frequency comb probe
Authors: Silva de Oliveira Vinicius , Silander Isak , Rutkowski Lucile , Soboń Grzegorz , Axner Ove , Lehmann Kevin K. , Foltynowicz Aleksandra 
Published: January 2024

AbstractAccurate parameters of molecular hot-band transitions, i.e., those
starting from vibrationally excited levels, are needed to accurately model
high-temperature spectra in astrophysics and combustion, yet laboratory spectra
measured at high temperatures are often unresolved and difficult to assign.
Optical-optical double-resonance (OODR) spectroscopy allows the measurement and
assignment of individual hot-band transitions from selectively pumped energy levels
without the need to heat the sample. However, previous demonstrations lacked either
sufficient resolution, spectral coverage, absorption sensitivity, or frequency
accuracy. Here we demonstrate OODR spectroscopy using a cavity-enhanced frequency
comb probe that combines all these advantages. We detect and assign sub-Doppler
transitions in the spectral range of the
3ν3 ← ν3 resonance of methane with
frequency precision and sensitivity more than an order of magnitude better than
before. This technique will provide high-accuracy data about excited states of a
wide range of molecules that is urgently needed for theoretical modeling of
high-temperature data and cannot be obtained using other methods.
Alveolar macrophage-expressed Plet1 is a driver of lung epithelial repair after viral pneumonia
Authors: Pervizaj-Oruqaj Learta , Selvakumar Balachandar , Ferrero Maximiliano Ruben , Heiner Monika , Malainou Christina , Glaser Rolf David , Wilhelm Jochen , Bartkuhn Marek , Weiss Astrid , Alexopoulos Ioannis , Witte Biruta , Gattenlöhner Stefan , Vadász István , Morty Rory Edward , Seeger Werner , Schermuly Ralph Theo , Vazquez-Armendariz Ana Ivonne , Herold Susanne 
Published: January 2024

AbstractInfluenza A virus (IAV) infection mobilizes bone marrow-derived macrophages (BMDM) that gradually undergo transition to tissue-resident alveolar macrophages (TR-AM) in the inflamed lung. Combining high-dimensional single-cell transcriptomics with complex lung organoid modeling, in vivo adoptive cell transfer, and BMDM-specific gene targeting, we found that transitioning (“regenerative”) BMDM and TR-AM highly express Placenta-expressed transcript 1 (Plet1). We reveal that Plet1 is released from alveolar macrophages, and acts as important mediator of macrophage-epithelial cross-talk during lung repair by inducing proliferation of alveolar epithelial cells and re-sealing of the epithelial barrier. Intratracheal administration of recombinant Plet1 early in the disease course attenuated viral lung injury and rescued mice from otherwise fatal disease, highlighting its therapeutic potential.
Asymmetric α-benzylation of cyclic ketones enabled by concurrent chemical aldol condensation and biocatalytic reduction
Authors: Liu Yunting , Ma Teng , Guo Zhongxu , Zhou Liya , Liu Guanhua , He Ying , Ma Li , Gao Jing , Bai Jing , Hollmann Frank , Jiang Yanjun 
Published: January 2024

AbstractChemoenzymatic cascade catalysis has emerged as a revolutionary tool for streamlining traditional retrosynthetic disconnections, creating new possibilities for the asymmetric synthesis of valuable chiral compounds. Here we construct a one-pot concurrent chemoenzymatic cascade by integrating organobismuth-catalyzed aldol condensation with ene-reductase (ER)-catalyzed enantioselective reduction, enabling the formal asymmetric α-benzylation of cyclic ketones. To achieve this, we develop a pair of enantiocomplementary ERs capable of reducing α-arylidene cyclic ketones, lactams, and lactones. Our engineered mutants exhibit significantly higher activity, up to 37-fold, and broader substrate specificity compared to the parent enzyme. The key to success is due to the well-tuned hydride attack distance/angle and, more importantly, to the synergistic proton-delivery triade of Tyr28-Tyr69-Tyr169. Molecular docking and density functional theory (DFT) studies provide important insights into the bioreduction mechanisms. Furthermore, we demonstrate the synthetic utility of the best mutants in the asymmetric synthesis of several key chiral synthons.
Quantifying negative selection in human 3ʹ UTRs uncovers constrained targets of RNA-binding proteins
Authors: Findlay Scott D. , Romo Lindsay , Burge Christopher B. 
Published: January 2024

AbstractMany non-coding variants associated with phenotypes occur in 3ʹ untranslated regions (3ʹ UTRs), and may affect interactions with RNA-binding proteins (RBPs) to regulate gene expression post-transcriptionally. However, identifying functional 3ʹ UTR variants has proven difficult. We use allele frequencies from the Genome Aggregation Database (gnomAD) to identify classes of 3ʹ UTR variants under strong negative selection in humans. We develop intergenic mutability-adjusted proportion singleton (iMAPS), a generalized measure related to MAPS, to quantify negative selection in non-coding regions. This approach, in conjunction with in vitro and in vivo binding data, identifies precise RBP binding sites, miRNA target sites, and polyadenylation signals (PASs) under strong selection. For each class of sites, we identify thousands of gnomAD variants under selection comparable to missense coding variants, and find that sites in core 3ʹ UTR regions upstream of the most-used PAS are under strongest selection. Together, this work improves our understanding of selection on human genes and validates approaches for interpreting genetic variants in human 3ʹ UTRs.
Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1
Authors: Ren Wenfeng , Xu Zilong , Chang Yating , Ju Fei , Wu Hongning , Liang Zhiqi , Zhao Min , Wang Naizhen , Lin Yanhua , Xu Chenhang , Chen Shengming , Rao Yipeng , Lin Chaolong , Yang Jianxin , Liu Pingguo , Zhang Jun , Huang Chenghao , Xia Ningshao 
Published: January 2024

AbstractPD-1 is a co-inhibitory receptor expressed by CD8+ T cells which limits their cytotoxicity. PD-L1 expression on cancer cells contributes to immune evasion by cancers, thus, understanding the mechanisms that regulate PD-L1 protein levels in cancers is important. Here we identify tumor-cell-expressed otubain-2 (OTUB2) as a negative regulator of antitumor immunity, acting through the PD-1/PD-L1 axis in various human cancers. Mechanistically, OTUB2 directly interacts with PD-L1 to disrupt the ubiquitination and degradation of PD-L1 in the endoplasmic reticulum. Genetic deletion of OTUB2 markedly decreases the expression of PD-L1 proteins on the tumor cell surface, resulting in increased tumor cell sensitivity to CD8+ T-cell-mediated cytotoxicity. To underscore relevance in human patients, we observe a significant correlation between OTUB2 expression and PD-L1 abundance in human non-small cell lung cancer. An inhibitor of OTUB2, interfering with its deubiquitinase activity without disrupting the OTUB2-PD-L1 interaction, successfully reduces PD-L1 expression in tumor cells and suppressed tumor growth. Together, these results reveal the roles of OTUB2 in PD-L1 regulation and tumor evasion and lays down the proof of principle for OTUB2 targeting as therapeutic strategy for cancer treatment.
Competition between inside-out unfolding and pathogenic aggregation in an amyloid-forming β-propeller
Authors: Saccuzzo Emily G. , Mebrat Mubark D. , Scelsi Hailee F. , Kim Minjoo , Ma Minh Thu , Su Xinya , Hill Shannon E. , Rheaume Elisa , Li Renhao , Torres Matthew P. , Gumbart James C. , Van Horn Wade D. , Lieberman Raquel L. 
Published: January 2024

AbstractStudies of folded-to-misfolded transitions using model protein systems reveal a range of unfolding needed for exposure of amyloid-prone regions for subsequent fibrillization. Here, we probe the relationship between unfolding and aggregation for glaucoma-associated myocilin. Mutations within the olfactomedin domain of myocilin (OLF) cause a gain-of-function, namely cytotoxic intracellular aggregation, which hastens disease progression. Aggregation by wild-type OLF (OLFWT) competes with its chemical unfolding, but only below the threshold where OLF loses tertiary structure. Representative moderate (OLFD380A) and severe (OLFI499F) disease variants aggregate differently, with rates comparable to OLFWT in initial stages of unfolding, and variants adopt distinct partially folded structures seen along the OLFWT urea-unfolding pathway. Whether initiated with mutation or chemical perturbation, unfolding propagates outward to the propeller surface. In sum, for this large protein prone to amyloid formation, the requirement for a conformational change to promote amyloid fibrillization leads to direct competition between unfolding and aggregation.
Observation and manipulation of quantum interference in a superconducting Kerr parametric oscillator
Authors: Iyama Daisuke , Kamiya Takahiko , Fujii Shiori , Mukai Hiroto , Zhou Yu , Nagase Toshiaki , Tomonaga Akiyoshi , Wang Rui , Xue Jiao-Jiao , Watabe Shohei , Kwon Sangil , Tsai Jaw-Shen 
Published: January 2024

AbstractQuantum tunneling is the phenomenon that makes superconducting circuits “quantum”. Recently, there has been a renewed interest in using quantum tunneling in phase space of a Kerr parametric oscillator as a resource for quantum information processing. Here, we report a direct observation of quantum interference induced by such tunneling and its dynamics in a planar superconducting circuit through Wigner tomography. We experimentally elucidate all essential properties of this quantum interference, such as mapping from Fock states to cat states, a temporal oscillation due to the pump detuning, as well as its characteristic Rabi oscillations and Ramsey fringes. Finally, we perform gate operations as manipulations of the observed quantum interference. Our findings lay the groundwork for further studies on quantum properties of superconducting Kerr parametric oscillators and their use in quantum information technologies.
MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation
Authors: Chi Wenna , Kang Na , Sheng Linlin , Liu Sichen , Tao Lei , Cao Xizhi , Liu Ye , Zhu Can , Zhang Yuming , Wu Bolong , Chen Ruiqun , Cheng Lili , Wang Jing , Sun Xiaolin , Liu Xiaohui , Deng Haiteng , Yang Jinliang , Li Zhanguo , Liu Wanli , Chen Ligong 
Published: January 2024

AbstractMonocarboxylate transporter 1 (MCT1) exhibits essential roles in cellular metabolism and energy supply. Although MCT1 is highly expressed in activated B cells, it is not clear how MCT1-governed monocarboxylates transportation is functionally coupled to antibody production during the glucose metabolism. Here, we report that B cell-lineage deficiency of MCT1 significantly influences the class-switch recombination (CSR), rendering impaired IgG antibody responses in Mct1f/fMb1Cre mice after immunization. Metabolic flux reveals that glucose metabolism is significantly reprogrammed from glycolysis to oxidative phosphorylation in Mct1-deficient B cells upon activation. Consistently, activation-induced cytidine deaminase (AID), is severely suppressed in Mct1-deficient B cells due to the decreased level of pyruvate metabolite. Mechanistically, MCT1 is required to maintain the optimal concentration of pyruvate to secure the sufficient acetylation of H3K27 for the elevated transcription of AID in activated B cells. Clinically, we found that MCT1 expression levels are significantly upregulated in systemic lupus erythematosus patients, and Mct1 deficiency can alleviate the symptoms of bm12-induced murine lupus model. Collectively, these results demonstrate that MCT1-mediated pyruvate metabolism is required for IgG antibody CSR through an epigenetic dependent AID transcription, revealing MCT1 as a potential target for vaccine development and SLE disease treatment.
Hijacking of internal calcium dynamics by intracellularly residing viral rhodopsins
Authors: Eria-Oliveira Ana-Sofia , Folacci Mathilde , Chassot Anne Amandine , Fedou Sandrine , Thézé Nadine , Zabelskii Dmitrii , Alekseev Alexey , Bamberg Ernst , Gordeliy Valentin , Sandoz Guillaume , Vivaudou Michel 
Published: January 2024

AbstractRhodopsins are ubiquitous light-driven membrane proteins with diverse functions, including ion transport. Widely distributed, they are also coded in the genomes of giant viruses infecting phytoplankton where their function is not settled. Here, we examine the properties of OLPVR1 (Organic Lake Phycodnavirus Rhodopsin) and two other type 1 viral channelrhodopsins (VCR1s), and demonstrate that VCR1s accumulate exclusively intracellularly, and, upon illumination, induce calcium release from intracellular IP3-dependent stores. In vivo, this light-induced calcium release is sufficient to remote control muscle contraction in VCR1-expressing tadpoles. VCR1s natively confer light-induced Ca2+ release, suggesting a distinct mechanism for reshaping the response to light of virus-infected algae. The ability of VCR1s to photorelease calcium without altering plasma membrane electrical properties marks them as potential precursors for optogenetics tools, with potential applications in basic research and medicine.