bluuebunny/crossref_metadata_2025_split huggingface dataset:
A propolis-derived small molecule ameliorates metabolic syndrome in obese mice by targeting the CREB/CRTC2 transcriptional complex
Authors: Chen Yaqiong , Wang Jiang , Wang Yibing , Wang Pengfei , Zhou Zan , Wu Rong , Xu Qian , You Hanyun , Liu Yaxin , Wang Lei , Zhou Lingqin , Wu Yuting , Hu Lihong , Liu Hong , Liu Yi 
Published: January 2022

AbstractThe molecular targets and mechanisms of propolis ameliorating metabolic syndrome are not fully understood. Here, we report that Brazilian green propolis reduces fasting blood glucose levels in obese mice by disrupting the formation of CREB/CRTC2 transcriptional complex, a key regulator of hepatic gluconeogenesis. Using a mammalian two-hybrid system based on CREB-CRTC2, we identify artepillin C (APC) from propolis as an inhibitor of CREB-CRTC2 interaction. Without apparent toxicity, APC protects mice from high fat diet-induced obesity, decreases fasting glucose levels, enhances insulin sensitivity and reduces lipid levels in the serum and liver by suppressing CREB/CRTC2-mediated both gluconeogenic and SREBP transcriptions. To develop more potential drugs from APC, we designed and found a novel compound, A57 that exhibits higher inhibitory activity on CREB-CRTC2 association and better capability of improving insulin sensitivity in obese animals, as compared with APC. In this work, our results indicate that CREB/CRTC2 is a suitable target for developing anti-metabolic syndrome drugs.
Zero-preserving imputation of single-cell RNA-seq data
Authors: Linderman George C. , Zhao Jun , Roulis Manolis , Bielecki Piotr , Flavell Richard A. , Nadler Boaz , Kluger Yuval 
Published: January 2022

AbstractA key challenge in analyzing single cell RNA-sequencing data is the large number of false zeros, where genes actually expressed in a given cell are incorrectly measured as unexpressed. We present a method based on low-rank matrix approximation which imputes these values while preserving biologically non-expressed genes (true biological zeros) at zero expression levels. We provide theoretical justification for this denoising approach and demonstrate its advantages relative to other methods on simulated and biological datasets.
A GATA4-regulated secretory program suppresses tumors through recruitment of cytotoxic CD8 T cells
Authors: Patel Rupesh S. , Romero Rodrigo , Watson Emma V. , Liang Anthony C. , Burger Megan , Westcott Peter M. K. , Mercer Kim L. , Bronson Roderick T. , Wooten Eric C. , Bhutkar Arjun , Jacks Tyler , Elledge Stephen J. 
Published: January 2022

AbstractThe GATA4 transcription factor acts as a master regulator of development of multiple tissues. GATA4 also acts in a distinct capacity to control a stress-inducible pro-inflammatory secretory program that is associated with senescence, a potent tumor suppression mechanism, but also operates in non-senescent contexts such as tumorigenesis. This secretory pathway is composed of chemokines, cytokines, growth factors, and proteases. Since GATA4 is deleted or epigenetically silenced in cancer, here we examine the role of GATA4 in tumorigenesis in mouse models through both loss-of-function and overexpression experiments. We find that GATA4 promotes non-cell autonomous tumor suppression in multiple model systems. Mechanistically, we show that Gata4-dependent tumor suppression requires cytotoxic CD8 T cells and partially requires the secreted chemokine CCL2. Analysis of transcriptome data in human tumors reveals reduced lymphocyte infiltration in GATA4-deficient tumors, consistent with our murine data. Notably, activation of the GATA4-dependent secretory program combined with an anti-PD-1 antibody robustly abrogates tumor growth in vivo.
Probing polaron-induced exciton quenching in TADF based organic light-emitting diodes
Authors: Hasan Monirul , Saggar Siddhartha , Shukla Atul , Bencheikh Fatima , Sobus Jan , McGregor Sarah K. M. , Adachi Chihaya , Lo Shih-Chun , Namdas Ebinazar B. 
Published: January 2022

AbstractPolaron-induced exciton quenching in thermally activated delayed fluorescence (TADF)-based organic light-emitting diodes (OLEDs) can lead to external quantum efficiency (EQE) roll-off and device degradation. In this study, singlet-polaron annihilation (SPA) and triplet-polaron annihilation (TPA) were investigated under steady-state conditions and their relative contributions to EQE roll-off were quantified, using experimentally obtained parameters. It is observed that both TPA and SPA can lead to efficiency roll-off in 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (4CzIPN) doped OLEDs. Charge imbalance and singlet-triplet annihilation (STA) were found to be the main contributing factors, whereas the device degradation process is mainly dominated by TPA. It is also shown that the impact of electric field-induced exciton dissociation is negligible under the DC operation regime (electric field < 0.5 MV cm−1). Through theoretical simulation, it is demonstrated that improvement to the charge recombination rate may reduce the effect of polaron-induced quenching, and thus significantly decrease the EQE roll-off.
A cortical cell ensemble in the posterior parietal cortex controls past experience-dependent memory updating
Authors: Suzuki Akinobu , Kosugi Sakurako , Murayama Emi , Sasakawa Eri , Ohkawa Noriaki , Konno Ayumu , Hirai Hirokazu , Inokuchi Kaoru 
Published: January 2022

AbstractWhen processing current sensory inputs, animals refer to related past experiences. Current information is then incorporated into the related neural network to update previously stored memories. However, the neuronal mechanism underlying the impact of memories of prior experiences on current learning is not well understood. Here, we found that a cellular ensemble in the posterior parietal cortex (PPC) that is activated during past experience mediates an interaction between past and current information to update memory through a PPC-anterior cingulate cortex circuit in mice. Moreover, optogenetic silencing of the PPC ensemble immediately after retrieval dissociated the interaction without affecting individual memories stored in the hippocampus and amygdala. Thus, a specific subpopulation of PPC cells represents past information and instructs downstream brain regions to update previous memories.
Asymmetric topological pumping in nonparaxial photonics
Authors: Cheng Qingqing , Wang Huaiqiang , Ke Yongguan , Chen Tao , Yu Ye , Kivshar Yuri S. , Lee Chaohong , Pan Yiming 
Published: January 2022

AbstractTopological photonics was initially inspired by the quantum-optical analogy between the Schrödinger equation for an electron wavefunction and the paraxial equation for a light beam. Here, we reveal an unexpected phenomenon in topological pumping observed in arrays of nonparaxial optical waveguides where the quantum-optical analogy becomes invalid. We predict theoretically and demonstrate experimentally an asymmetric topological pumping when the injected field transfers from one side of the waveguide array to the other side whereas the reverse process is unexpectedly forbidden. Our finding could open an avenue for exploring topological photonics that enables nontrivial topological phenomena and designs in photonics driven by nonparaxiality.
Mid-Cretaceous marine Os isotope evidence for heterogeneous cause of oceanic anoxic events
Authors: Matsumoto Hironao , Coccioni Rodolfo , Frontalini Fabrizio , Shirai Kotaro , Jovane Luigi , Trindade Ricardo , Savian Jairo F. , Kuroda Junichiro 
Published: January 2022

AbstractDuring the mid-Cretaceous, the Earth experienced several environmental perturbations, including an extremely warm climate and Oceanic Anoxic Events (OAEs). Submarine volcanic episodes associated with formation of large igneous provinces (LIPs) may have triggered these perturbations. The osmium isotopic ratio (187Os/188Os) is a suitable proxy for tracing hydrothermal activity associated with the LIPs formation, but187Os/188Os data from the mid-Cretaceous are limited to short time intervals. Here we provide a continuous high-resolution marine187Os/188Os record covering all mid-Cretaceous OAEs. Several OAEs (OAE1a, Wezel and Fallot events, and OAE2) correspond to unradiogenic187Os/188Os shifts, suggesting that they were triggered by massive submarine volcanic episodes. However, minor OAEs (OAE1c and OAE1d), which do not show pronounced unradiogenic187Os/188Os shifts, were likely caused by enhanced monsoonal activity. Because the subaerial LIPs volcanic episodes and Circum-Pacific volcanism correspond to the highest temperature andpCO2during the mid-Cretaceous, they may have caused the hot mid-Cretaceous climate.
Cyclopentadienyl coordination induces unexpected ionic Am−N bonding in an americium bipyridyl complex
Authors: Long Brian N. , Beltrán-Leiva María J. , Celis-Barros Cristian , Sperling Joseph M. , Poe Todd N. , Baumbach Ryan E. , Windorff Cory J. , Albrecht-Schönzart Thomas E. 
Published: January 2022

AbstractVariations in bonding between trivalent lanthanides and actinides is critical for reprocessing spent nuclear fuel. The ability to tune bonding and the coordination environment in these trivalent systems is a key factor in identifying a solution for separating lanthanides and actinides. Coordination of 4,4′−bipyridine (4,4′−bpy) and trimethylsilylcyclopentadienide (Cp′) to americium introduces unexpectedly ionic Am−N bonding character and unique spectroscopic properties. Here we report the structural characterization of (Cp′3Am)2(μ − 4,4′−bpy) and its lanthanide analogue, (Cp′3Nd)2(μ − 4,4′−bpy), by single-crystal X-ray diffraction. Spectroscopic techniques in both solid and solution phase are performed in conjunction with theoretical calculations to probe the effects the unique coordination environment has on the electronic structure.
Controlling the length of porphyrin supramolecular polymers via coupled equilibria and dilution-induced supramolecular polymerization
Authors: Weyandt Elisabeth , Leanza Luigi , Capelli Riccardo , Pavan Giovanni M. , Vantomme Ghislaine , Meijer E. W. 
Published: January 2022

AbstractMulti-component systems often display convoluted behavior, pathway complexity and coupled equilibria. In recent years, several ways to control complex systems by manipulating the subtle balances of interaction energies between the individual components have been explored and thereby shifting the equilibrium between different aggregate states. Here we show the enantioselective chain-capping and dilution-induced supramolecular polymerization with a Zn2+-porphyrin-based supramolecular system when going from long, highly cooperative supramolecular polymers to short, disordered aggregates by adding a monotopic Mn3+-porphyrin monomer. When mixing the zinc and manganese centered monomers, the Mn3+-porphyrins act as chain-cappers for Zn2+-porphyrin supramolecular polymers, effectively hindering growth of the copolymer and reducing the length. Upon dilution, the interaction between chain-capper and monomers weakens as the equilibria shift and long supramolecular polymers form again. This dynamic modulation of aggregate morphology and length is achieved through enantioselectivity in the aggregation pathways and concentration-sensitive equilibria. All-atom and coarse-grained molecular simulations provide further insights into the mixing of the species and their exchange dynamics. Our combined experimental and theoretical approach allows for precise control of molecular self-assembly and chiral discrimination in complex systems.
Structural basis of BAK activation in mitochondrial apoptosis initiation
Authors: Singh Geetika , Guibao Cristina D. , Seetharaman Jayaraman , Aggarwal Anup , Grace Christy R. , McNamara Dan E. , Vaithiyalingam Sivaraja , Waddell M. Brett , Moldoveanu Tudor 
Published: January 2022

AbstractBCL-2 proteins regulate mitochondrial poration in apoptosis initiation. How the pore-forming BCL-2 Effector BAK is activated remains incompletely understood mechanistically. Here we investigate autoactivation and direct activation by BH3-only proteins, which cooperate to lower BAK threshold in membrane poration and apoptosis initiation. We define in trans BAK autoactivation as the asymmetric “BH3-in-groove” triggering of dormant BAK by active BAK. BAK autoactivation is mechanistically similar to direct activation. The structure of autoactivated BAK BH3-BAK complex reveals the conformational changes leading to helix α1 destabilization, which is a hallmark of BAK activation. Helix α1 is destabilized and restabilized in structures of BAK engaged by rationally designed, high-affinity activating and inactivating BID-like BH3 ligands, respectively. Altogether our data support the long-standing hit-and-run mechanism of BAK activation by transient binding of BH3-only proteins, demonstrating that BH3-induced structural changes are more important in BAK activation than BH3 ligand affinity.
Canonical WNT signaling-dependent gating of MYC requires a noncanonical CTCF function at a distal binding site
Authors: Chachoua Ilyas , Tzelepis Ilias , Dai Hao , Lim Jia Pei , Lewandowska-Ronnegren Anna , Casagrande Felipe Beccaria , Wu Shuangyang , Vestlund Johanna , Mallet de Lima Carolina Diettrich , Bhartiya Deeksha , Scholz Barbara A. , Martino Mirco , Mehmood Rashid , Göndör Anita 
Published: January 2022

AbstractAbnormal WNT signaling increases MYC expression in colon cancer cells in part via oncogenic super-enhancer-(OSE)-mediated gating of the active MYC to the nuclear pore in a poorly understood process. We show here that the principal tenet of the WNT-regulated MYC gating, facilitating nuclear export of the MYC mRNA, is regulated by a CTCF binding site (CTCFBS) within the OSE to confer growth advantage in HCT-116 cells. To achieve this, the CTCFBS directs the WNT-dependent trafficking of the OSE to the nuclear pore from intra-nucleoplasmic positions in a stepwise manner. Once the OSE reaches a peripheral position, which is triggered by a CTCFBS-mediated CCAT1 eRNA activation, its final stretch (≤0.7 μm) to the nuclear pore requires the recruitment of AHCTF1, a key nucleoporin, to the CTCFBS. Thus, a WNT/ß-catenin-AHCTF1-CTCF-eRNA circuit enables the OSE to promote pathological cell growth by coordinating the trafficking of the active MYC gene within the 3D nuclear architecture.
Mapping the broadband circular dichroism of copolymer films with supramolecular chirality in time and space
Authors: Morgenroth Marius , Scholz Mirko , Cho Min Ju , Choi Dong Hoon , Oum Kawon , Lenzer Thomas 
Published: January 2022

AbstractMeasurements of the electronic circular dichroism (CD) are highly sensitive to the absolute configuration and conformation of chiral molecules and supramolecular assemblies and have therefore found widespread application in the chemical and biological sciences. Here, we demonstrate an approach to simultaneously follow changes in the CD and absorption response of photoexcited systems over the ultraviolet−visible spectral range with 100 fs time resolution. We apply the concept to chiral polyfluorene copolymer thin films and track their electronic relaxation in detail. The transient CD signal stems from the supramolecular response of the system and provides information regarding the recovery of the electronic ground state. This allows for a quantification of singlet−singlet annihilation and charge-pair formation processes. Spatial mapping of chiral domains on femtosecond time scales with a resolution of 50 μm and diffraction-limited steady-state imaging of the circular dichroism and the circularly polarised luminescence (CPL) of the films is demonstrated.
Signatures of enhanced out-of-plane polarization in asymmetric BaTiO3 superlattices integrated on silicon
Authors: Chen Binbin , Gauquelin Nicolas , Strkalj Nives , Huang Sizhao , Halisdemir Ufuk , Nguyen Minh Duc , Jannis Daen , Sarott Martin F. , Eltes Felix , Abel Stefan , Spreitzer Matjaž , Fiebig Manfred , Trassin Morgan , Fompeyrine Jean , Verbeeck Johan , Huijben Mark , Rijnders Guus , Koster Gertjan 
Published: January 2022

AbstractIn order to bring the diverse functionalities of transition metal oxides into modern electronics, it is imperative to integrate oxide films with controllable properties onto the silicon platform. Here, we present asymmetric LaMnO3/BaTiO3/SrTiO3 superlattices fabricated on silicon with layer thickness control at the unit-cell level. By harnessing the coherent strain between the constituent layers, we overcome the biaxial thermal tension from silicon and stabilize c-axis oriented BaTiO3 layers with substantially enhanced tetragonality, as revealed by atomically resolved scanning transmission electron microscopy. Optical second harmonic generation measurements signify a predominant out-of-plane polarized state with strongly enhanced net polarization in the tricolor superlattices, as compared to the BaTiO3 single film and conventional BaTiO3/SrTiO3 superlattice grown on silicon. Meanwhile, this coherent strain in turn suppresses the magnetism of LaMnO3 as the thickness of BaTiO3 increases. Our study raises the prospect of designing artificial oxide superlattices on silicon with tailored functionalities.
Robust differentiation of human enteroendocrine cells from intestinal stem cells
Authors: Zeve Daniel , Stas Eric , de Sousa Casal Joshua , Mannam Prabhath , Qi Wanshu , Yin Xiaolei , Dubois Sarah , Shah Manasvi S. , Syverson Erin P. , Hafner Sophie , Karp Jeffrey M. , Carlone Diana L. , Ordovas-Montanes Jose , Breault David T. 
Published: January 2022

AbstractEnteroendocrine (EE) cells are the most abundant hormone-producing cells in humans and are critical regulators of energy homeostasis and gastrointestinal function. Challenges in converting human intestinal stem cells (ISCs) into functional EE cells, ex vivo, have limited progress in elucidating their role in disease pathogenesis and in harnessing their therapeutic potential. To address this, we employed small molecule targeting of the endocannabinoid receptor signaling pathway, JNK, and FOXO1, known to mediate endodermal development and/or hormone production, together with directed differentiation of human ISCs from the duodenum and rectum. We observed marked induction of EE cell differentiation and gut-derived expression and secretion of SST, 5HT, GIP, CCK, GLP-1 and PYY upon treatment with various combinations of three small molecules: rimonabant, SP600125 and AS1842856. Robust differentiation strategies capable of driving human EE cell differentiation is a critical step towards understanding these essential cells and the development of cell-based therapeutics.
The RNA methyltransferase METTL8 installs m3C32 in mitochondrial tRNAsThr/Ser(UCN) to optimise tRNA structure and mitochondrial translation
Authors: Kleiber Nicole , Lemus-Diaz Nicolas , Stiller Carina , Heinrichs Marleen , Mai Mandy Mong-Quyen , Hackert Philipp , Richter-Dennerlein Ricarda , Höbartner Claudia , Bohnsack Katherine E. , Bohnsack Markus T. 
Published: January 2022

AbstractModified nucleotides in tRNAs are important determinants of folding, structure and function. Here we identify METTL8 as a mitochondrial matrix protein and active RNA methyltransferase responsible for installing m3C32 in the human mitochondrial (mt-)tRNAThr and mt-tRNASer(UCN). METTL8 crosslinks to the anticodon stem loop (ASL) of many mt-tRNAs in cells, raising the question of how methylation target specificity is achieved. Dissection of mt-tRNA recognition elements revealed U34G35 and t6A37/(ms2)i6A37, present concomitantly only in the ASLs of the two substrate mt-tRNAs, as key determinants for METTL8-mediated methylation of C32. Several lines of evidence demonstrate the influence of U34, G35, and the m3C32 and t6A37/(ms2)i6A37 modifications in mt-tRNAThr/Ser(UCN) on the structure of these mt-tRNAs. Although mt-tRNAThr/Ser(UCN) lacking METTL8-mediated m3C32 are efficiently aminoacylated and associate with mitochondrial ribosomes, mitochondrial translation is mildly impaired by lack of METTL8. Together these results define the cellular targets of METTL8 and shed new light on the role of m3C32 within mt-tRNAs.
Engineering of atomic-scale flexoelectricity at grain boundaries
Authors: Wu Mei , Zhang Xiaowei , Li Xiaomei , Qu Ke , Sun Yuanwei , Han Bo , Zhu Ruixue , Gao Xiaoyue , Zhang Jingmin , Liu Kaihui , Bai Xuedong , Li Xin-Zheng , Gao Peng 
Published: January 2022

AbstractFlexoelectricity is a type of ubiquitous and prominent electromechanical coupling, pertaining to the electrical polarization response to mechanical strain gradients that is not restricted by the symmetry of materials. However, large elastic deformation is usually difficult to achieve in most solids, and the strain gradient at minuscule is challenging to control. Here, we exploit the exotic structural inhomogeneity of grain boundary to achieve a huge strain gradient (~1.2 nm−1) within 3–4-unit cells, and thus obtain atomic-scale flexoelectric polarization of up to ~38 μC cm−2 at a 24° LaAlO3 grain boundary. Accompanied by the generation of the nanoscale flexoelectricity, the electronic structures of grain boundaries also become different. Hence, the flexoelectric effect at grain boundaries is essential to understand the electrical activities of oxide ceramics. We further demonstrate that for different materials, altering the misorientation angles of grain boundaries enables tunable strain gradients at the atomic scale. The engineering of grain boundaries thus provides a general and feasible pathway to achieve tunable flexoelectricity.
Fine pore engineering in a series of isoreticular metal-organic frameworks for efficient C2H2/CO2 separation
Authors: Wang Jun , Zhang Yan , Su Yun , Liu Xing , Zhang Peixin , Lin Rui-Biao , Chen Shixia , Deng Qiang , Zeng Zheling , Deng Shuguang , Chen Banglin 
Published: January 2022

AbstractThe separation of C2H2/CO2 is not only industrially important for acetylene purification but also scientifically challenging owing to their high similarities in physical properties and molecular sizes. Ultramicroporous metal-organic frameworks (MOFs) can exhibit a pore confinement effect to differentiate gas molecules of similar size. Herein, we report the fine-tuning of pore sizes in sub-nanometer scale on a series of isoreticular MOFs that can realize highly efficient C2H2/CO2 separation. The subtle structural differences lead to remarkable adsorption performances enhancement. Among four MOF analogs, by integrating appropriate pore size and specific binding sites, [Cu(dps)2(SiF6)] (SIFSIX-dps-Cu, SIFSIX = SiF62-, dps = 4.4’-dipyridylsulfide, also termed as NCU-100) exhibits the highest C2H2 uptake capacity and C2H2/CO2 selectivity. At room temperature, the pore space of SIFSIX-dps-Cu significantly inhibits CO2 molecules but takes up a large amount of C2H2 (4.57 mmol g−1), resulting in a high IAST selectivity of 1787 for C2H2/CO2 separation. The multiple host-guest interactions for C2H2 in both inter- and intralayer cavities are further revealed by dispersion-corrected density functional theory and grand canonical Monte Carlo simulations. Dynamic breakthrough experiments show a clean C2H2/CO2 separation with a high C2H2 working capacity of 2.48 mmol g−1.