bluuebunny/crossref_metadata_2025 huggingface dataset:
Extending Instrumental Sea‐Level Records Using Coral Microatolls, an Example From Southeast Asia
Authors: Majewski J. M. , Meltzner A. J. , Switzer A. D. , Shaw T. A. , Li T. , Bradley S. , Walker J. S. , Kopp R. E. , Samanta D. , Natawidjaja D. H. , Suwargadi B. W. , Horton B. P.
Published: January 2022

The small number of reliable long‐term (i.e., >50 yrs) tide gauges in tropical locations is a major source of uncertainty in modern sea‐level change. Coral microatolls record relative sea‐level (RSL) change over their lifetimes and have the potential to extend the instrumental record. Here, we examined a 20th and 21st century RSL record from two living coral microatolls from Mapur Island, Indonesia, which produced 16 sea‐level index points. We validated and combined the living coral microatoll data with tide gauge data to show RSL at Mapur Island was 0.0 ± 1.6 mm/yr (2σ) from 1915 to 1990 and 1.0 ± 2.1 mm/yr (2σ) from 1990 to 2019. Through the addition of microatoll RSL data we extended the record of modern sea‐level change by over 50 years and reduced its uncertainty by ∼50%.
The Role of Metamorphic Fluid in Tectonic Tremor Along the Alpine Fault, New Zealand
Authors: Chapman Timothy , Milan Luke , Vry Julie
Published: January 2022

The production of H2O during metamorphism along active plate boundaries is inferred to contribute to low‐frequency tectonic tremor. This study combines predictions from phase equilibria and mechanical modeling of coincident volume changes to investigate links of tremor with hydrofracturing and fluid migration under the actively forming Southern Alps, New Zealand. The posited location of metamorphic fluid production correlates with published geophysical images of inferred permeability enhancement, fluid accumulation and potential fluid flow. As the hanging‐wall rocks are translated toward the surface by motion along the Alpine Fault, they can undergo metamorphic reactions that involve positive volume changes. Production of metamorphic fluids leads to hydrofracturing and the development of tremor hypocenters in regions along, and above deep reflectors of the Alpine Fault. The capacity of metamorphic rocks to generate or consume fluid along portions of the pressure–temperature path exerts a fundamental control on the distribution of stresses in the crust.
Statistical Behavior of Large‐Scale Ionospheric Disturbances From High Latitudes to Mid‐Latitudes During Geomagnetic Storms Using 20‐yr GNSS‐TEC Data: Dependence on Season and Storm Intensity
Authors: Shinbori Atsuki , Otsuka Yuichi , Sori Takuya , Tsugawa Takuya , Nishioka Michi
Published: January 2022

To establish the statistical behavior of ionospheric TEC variations from high latitudes to mid‐latitudes during the main and recovery phases of geomagnetic storms, we conducted a superposed epoch analysis of interplanetary magnetic field, solar wind, geomagnetic indices (AE and SYM‐H), and global navigation satellite system (GNSS)‐total electron content (TEC) data for 20 yr (2000–2019). In this study, we identify 663 geomagnetic storm events with the minimum SYM‐H value of less than −40 nT and investigate the characteristics of the TEC variations for the weak (−60 ≤ SYM‐Hmin < −40 nT), moderate (−100 ≤ SYM‐Hmin < −60 nT), and strong (−150 ≤ SYM‐Hmin < −100 nT) geomagnetic storms. The main results obtained from the present study are as follows: (a) The TEC enhancements related to the tongue of ionization (TOI), auroral oval, and storm‐enhanced density (SED) plume are more dominant in winter than in summer during the main phase of geomagnetic storms. (b) The structure of the mid‐latitude trough in the nighttime sector becomes unclear in winter. (c) The TEC depletion at auroral and mid‐latitudes (40°–70° GMLAT: geomagnetic latitude) starts to appear in the morning sector (8–10 hr GMLT: geomagnetic local time) during the main phase of geomagnetic storms and the decreased region extends in the lower latitude and GMLT directions with time. The negative storm activity tends to be enhanced significantly as the storm intensity becomes larger. The activity of the TEC depletion is dominant in summer than in winter, which is agreement with the classical ionospheric storm scenario.
Meteotsunamis in Orography‐Free, Flat Bathymetry and Warming Climate Conditions
Authors: Denamiel Cléa , Tojčić Iva , Vilibić Ivica
Published: January 2022

Due to a lack of suitable coupled atmosphere‐ocean modeling tools, the atmospheric source mechanisms that trigger the potentially destructive meteotsunami waves – which occur with periods ranging from a few minutes to a few hours – have remained partially unexplored until recently. In this process‐oriented numerical work we therefore investigate and quantify the impacts of orography and extreme climate changes on the generation and propagation of the atmospheric pressure disturbances that occurred during six different historical meteotsunami events in the Adriatic Sea. In addition, the impact of bathymetry, and hence Proudman resonance, on the propagation of the meteotsunami waves is investigated for the same ensemble of events. Our main findings can be summarized as follows: (a) Removing the mountains does not have a strong effect on either the generation or propagation of the meteotsunamigenic disturbances but may slightly increase their intensity, especially over land; (b) Extreme climate warming has the potential to increase the intensity of both atmospheric disturbances and meteotsunami waves near sensitive coastal areas; while (c) Flattening the bathymetry of the deepest Adriatic Sea tends to deflect the meteotsunami waves away from sensitive harbor locations. Such sensitivity studies, if generalized to other geographic locations with a higher number of events, may provide new insights into the still unknown physics of meteotsunami generation.
Reply to Comment by Azor et al. on “On the Rootless Nature of a Devonian Suture in SW Iberia (Ossa‐Morena Complex, Variscan Orogen): Geometry and Kinematics of the Azuaga Fault”
Authors: Fernández Rubén Díez , Fernández Carlos , Arenas Ricardo , Novo‐Fernández Irene
Published: January 2022

Geological mapping, structural data, and analytical modeling by Díez Fernández et al. (2021),https://doi.org/10.1029/2021tc006791supported that the Central Unit belonged to a rootless Devonian suture zone contiguous to the SW of its exposure and under the upper section of the footwall to the Azuaga Fault. Late exhumation of the Central Unit was via extrusion from the upper‐middle crust under inclined triclinic sinistral transpression, which favored upright folding of the suture zone. Azor and coworkers argue that the upright folds that affect the Central Unit are local, despite geological maps and structural data demonstrate they are km‐scale and occur all across the Central Unit. Besides ignoring structural data regarding the kinematics of the Azuaga Fault, Azor et al. (2022),https://doi.org/10.1029/2021TC006982fail to recognize the net upthrown movement of the NE side of the Azuaga Fault, as the Central Unit in that side is juxtaposed against syn‐orogenic strata that rest unconformably onto other metamorphic units in the SW side of the fault. Seismic data that image the Central Unit as a NE‐dipping rock package is used as an argument against the proposal by Díez Fernández et al. (2021),https://doi.org/10.1029/2021tc006791. However, the section of the Central Unit those data account for, are from a different part of the Central Unit, the real dip of some structures in the seismic image is not properly interpreted, and the model by Díez Fernández et al. (2021),https://doi.org/10.1029/2021tc006791is compatible with a Central Unit that also dips to the NE. Overall, the model proposed by Díez Fernández et al. (2021),https://doi.org/10.1029/2021tc006791remains valid.
Targeting prooxidant MnSOD effect inhibits triple-negative breast cancer (TNBC) progression and M2 macrophage functions under the oncogenic stress
Authors: Al Haq Aushia Tanzih , Tseng Hong-Yu , Chen Li-Mei , Wang Chien-Chia , Hsu Hsin-Ling
Published: January 2022

Triple-negative breast cancer (TNBC) has been shown with high mitochondrial oxidative phosphorylation and production of reactive oxygen species (ROS). MnSOD (SOD2) is a mitochondrial antioxidant defense that has been implicated in inhibition of human malignancies. However, the impact of MnSOD on immunosuppressive macrophage functions and TNBC aggressiveness has never been explored. We found here that SOD2high is primarily observed in the aggressive subtypes of HER2(+) breast cancers and TNBCs patients. Further analyses demonstrated that the oncoprotein multiple copies in T-cell malignancy-1 (MCT-1 or MCTS1) induces mitochondrial superoxide dismutase (MnSOD) in TNBC cells by stabilizing the transcription factor Nrf2. SOD2high/MCTS1high expression correlates with a poor prognosis in breast cancer patients. MnSOD in TNBC cells functions as a prooxidant peroxidase that increases mitochondrial ROS (mROS) and adaptation to oxidative stress under the oncogenic effect. Interleukin-6 (IL-6) in the MCT-1 pathway elevates Nrf2/MnSOD and mROS levels. Knockdown of MnSOD inhibits TNBC cell invasion, breast cancer stem cells (BCSCs), mROS, and IL-6 excretion promoted by MCT-1. TNBC cells deficient in MnSOD prevent the polarization and chemotaxis of M2 macrophages but improve the ability of M1 macrophages to engulf cancer cells. Quenching mROS with MitoQ, a mitochondria-targeted non-metal-based antioxidant MnSOD mimics, effectively suppresses BCSCs and M2 macrophage invasion exacerbated by MnSOD and MCT-1. Consistently, silencing MnSOD impedes TNBC progression and intratumoral M2 macrophage infiltration. We revealed a novel stratagem for TNBC management involving targeting the MCT-1 oncogene-induced mitochondrial prooxidant MnSOD pathway, which prevents the development of an immunosuppressive tumor microenvironment.
Hydrophilic nanoparticles that kill bacteria while sparing mammalian cells reveal the antibiotic role of nanostructures
Authors: Jiang Yunjiang , Zheng Wan , Tran Keith , Kamilar Elizabeth , Bariwal Jitender , Ma Hairong , Liang Hongjun
Published: January 2022

To dissect the antibiotic role of nanostructures from chemical moieties belligerent to both bacterial and mammalian cells, here we show the antimicrobial activity and cytotoxicity of nanoparticle-pinched polymer brushes (NPPBs) consisting of chemically inert silica nanospheres of systematically varied diameters covalently grafted with hydrophilic polymer brushes that are non-toxic and non-bactericidal. Assembly of the hydrophilic polymers into nanostructured NPPBs doesn’t alter their amicability with mammalian cells, but it incurs a transformation of their antimicrobial potential against bacteria, including clinical multidrug-resistant strains, that depends critically on the nanoparticle sizes. The acquired antimicrobial potency intensifies with small nanoparticles but subsides quickly with large ones. We identify a threshold size (dsilica ~ 50 nm) only beneath which NPPBs remodel bacteria-mimicking membrane into 2D columnar phase, the epitome of membrane pore formation. This study illuminates nanoengineering as a viable approach to develop nanoantibiotics that kill bacteria upon contact yet remain nontoxic when engulfed by mammalian cells.
Revisiting silk: a lens-free optical physical unclonable function
Authors: Kim Min Seok , Lee Gil Ju , Leem Jung Woo , Choi Seungho , Kim Young L. , Song Young Min
Published: January 2022

For modern security, devices, individuals, and communications require unprecedentedly unique identifiers and cryptographic keys. One emerging method for guaranteeing digital security is to take advantage of a physical unclonable function. Surprisingly, native silk, which has been commonly utilized in everyday life as textiles, can be applied as a unique tag material, thereby removing the necessary apparatus for optical physical unclonable functions, such as an objective lens or a coherent light source. Randomly distributed fibers in silk generate spatially chaotic diffractions, forming self-focused spots on the millimeter scale. The silk-based physical unclonable function has a self-focusing, low-cost, and eco-friendly feature without relying on pre-/post-process for security tag creation. Using these properties, we implement a lens-free, optical, and portable physical unclonable function with silk identification cards and study its characteristics and reliability in a systemic manner. We further demonstrate the feasibility of the physical unclonable functions in two modes: authentication and data encryption.
Breaking constraint of mammalian axial formulae
Authors: Hauswirth Gabriel M. , Garside Victoria C. , Wong Lisa S. F. , Bildsoe Heidi , Manent Jan , Chang Yi-Cheng , Nefzger Christian M. , Firas Jaber , Chen Joseph , Rossello Fernando J. , Polo Jose M. , McGlinn Edwina
Published: January 2022

The vertebral column of individual mammalian species often exhibits remarkable robustness in the number and identity of vertebral elements that form (known as axial formulae). The genetic mechanism(s) underlying this constraint however remain ill-defined. Here, we reveal the interplay of three regulatory pathways (Gdf11, miR-196 and Retinoic acid) is essential in constraining total vertebral number and regional axial identity in the mouse, from cervical through to tail vertebrae. All three pathways have differing control over Hox cluster expression, with heterochronic and quantitative changes found to parallel changes in axial identity. However, our work reveals an additional role for Hox genes in supporting axial elongation within the tail region, providing important support for an emerging view that mammalian Hox function is not limited to imparting positional identity as the mammalian body plan is laid down. More broadly, this work provides a molecular framework to interrogate mechanisms of evolutionary change and congenital anomalies of the vertebral column.
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

The 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

A 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

The 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

Polaron-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

When 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

Topological 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

During 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

Variations 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

Multi-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

BCL-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

Abnormal 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

Measurements 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

In 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

Enteroendocrine (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

Modified 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

Flexoelectricity 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

The 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.
Berberine bridge enzyme-like oxidase-catalysed double bond isomerization acts as the pathway switch in cytochalasin synthesis
Authors: Zhang Jin-Mei , Liu Xuan , Wei Qian , Ma Chuanteng , Li Dehai , Zou Yi
Published: January 2022

Cytochalasans (CYTs), as well as their polycyclic (pcCYTs) and polymerized (meCYTs) derivatives, constitute one of the largest families of fungal polyketide-nonribosomal peptide (PK-NRP) hybrid natural products. However, the mechanism of chemical conversion from mono-CYTs (moCYTs) to both pcCYTs and meCYTs remains unknown. Here, we show the first successful example of the reconstitution of the CYT core backbone as well as the whole pathway in a heterologous host. Importantly, we also describe the berberine bridge enzyme (BBE)-like oxidase AspoA, which uses Glu538 as a general acid biocatalyst to catalyse an unusual protonation-driven double bond isomerization reaction and acts as a switch to alter the native (for moCYTs) and nonenzymatic (for pcCYTs and meCYTs) pathways to synthesize aspochalasin family compounds. Our results present an unprecedented function of BBE-like enzymes and highly suggest that the isolated pcCYTs and meCYTs are most likely artificially derived products.
The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage
Authors: Girard Romain , Tremblay Sarah , Noll Christophe , St-Jean Stéphanie , Jones Christine , Gélinas Yves , Maloum-Rami Faïza , Perreault Nathalie , Laplante Mathieu , Carpentier André C. , Boudreau François
Published: January 2022

The transcription factor hepatocyte nuclear factor 4 A (HNF4A) controls the metabolic features of several endodermal epithelia. Both HNF4A and HNF4G are redundant in the intestine and it remains unclear whether HNF4A alone controls intestinal lipid metabolism. Here we show that intestinal HNF4A is not required for intestinal lipid metabolism per se, but unexpectedly influences whole-body energy expenditure in diet-induced obesity (DIO). Deletion of intestinal HNF4A caused mice to become DIO-resistant with a preference for fat as an energy substrate and energetic changes in association with white adipose tissue (WAT) beiging. Intestinal HNF4A is crucial for the fat-induced release of glucose-dependent insulinotropic polypeptide (GIP), while the reintroduction of a stabilized GIP analog rescues the DIO resistance phenotype of the mutant mice. Our study provides evidence that intestinal HNF4A plays a non-redundant role in whole-body lipid homeostasis and points to a non-cell-autonomous regulatory circuit for body-fat management.
Signatures of selection in recently domesticated macadamia
Authors: Lin Jishan , Zhang Wenping , Zhang Xingtan , Ma Xiaokai , Zhang Shengcheng , Chen Shuai , Wang Yibin , Jia Haifeng , Liao Zhenyang , Lin Jing , Zhu Mengting , Xu Xiuming , Cai Mingxing , Zeng Hui , Wan Jifeng , Yang Weihai , Matsumoto Tracie , Hardner Craig , Nock Catherine J. , Ming Ray
Published: January 2022

Macadamia is a high value nut crop that is recently domesticated, ideal for testing the effect of artificial selection. Here, we sequence the genome of Hawaiian cultivar ‘Kau’ and assemble into 794 Mb in 14 pseudo-chromosomes with 37,728 genes. Genome analysis reveals a whole-genome duplication event, occurred 46.8 million years ago. Gene expansions occurred in gene families involves in fatty acid biosynthesis. Gene duplication of MADS-Box transcription factors in proanthocyanidin biosynthesis are relevant for seed coat development. Genome re-sequencing of 112 accessions reveals the origin of Hawaiian cultivars from Mount Bauple in southeast Queensland in Australia. Selective sweeps are detected in macadamia cultivars, including genes involved in fatty acid biosynthesis, seed coat development, and heat stress response. Such strong effects of artificial selection in few generations reveals the genomic basis for ‘one-step operation’ for clonal crop domestication. The knowledge gained could accelerate domestication of new crops from wild species.
Gaps and roadmap of novel neuromodulation targets for treatment of gait in Parkinson’s disease
Authors: Cury Rubens Gisbert , Pavese Nicola , Aziz Tipu Z. , Krauss Joachim K. , Moro Elena ,   the Neuromodulation of Gait Study Group from Movement Disorders Society
Published: January 2022

Gait issues in Parkinson’s disease (PD) are common and can be highly disabling. Although levodopa and deep brain stimulation (DBS) of the subthalamic nucleus and the globus pallidus internus have been established therapies for addressing the motor symptoms of PD, their effects on gait are less predictable and not well sustained with disease progression. Given the high prevalence of gait impairment in PD and the limitations in currently approved therapies, there has been considerable interest in alternative neuromodulation targets and techniques. These have included DBS of pedunculopontine nucleus and substantia nigra pars reticulata, spinal cord stimulation, non-invasive modulation of cortical regions and, more recently, vagus nerve stimulation. However, successes and failures have also emerged with these approaches. Current gaps and controversies are related to patient selection, optimal electrode placement within the target, placebo effects and the optimal programming parameters. Additionally, recent advances in pathophysiology of oscillation dynamics have driven new models of closed-loop DBS systems that may or may not be applicable to gait issues. Our aim is to describe approaches, especially neuromodulation procedures, and emerging challenges to address PD gait issues beyond subthalamic nucleus and the globus pallidus internus stimulation.
Distanced self-talk increases rational self-interest
Authors: Gainsburg Izzy , Sowden Walter J. , Drake Brittany , Herold Warren , Kross Ethan
Published: January 2022

Does stepping back to evaluate a situation from a distanced perspective lead us to be selfish or fair? This question has been of philosophical interest for centuries, and, more recently, the focus of extensive empirical inquiry. Yet, extant research reveals a puzzle: some studies suggest that adopting a distanced perspective will produce more rationally self-interested behavior, whereas others suggest that it will produce more impartial behavior. Here we adjudicate between these perspectives by testing the effects of adopting a third-person perspective on decision making in a task that pits rational self-interest against impartiality: the dictator game. Aggregating across three experiments (N = 774), participants who used third-person (i.e., distanced) vs. first-person (i.e., immersed) self-talk during the dictator game kept more money for themselves. We discuss these results in light of prior research showing that psychological distance can promote cooperation and fairmindedness and how the effect of psychological distance on moral decision-making may be sensitive to social context.
Maximum 11C-methionine PET uptake as a prognostic imaging biomarker for newly diagnosed and untreated astrocytic glioma
Authors: Nakajo Kosuke , Uda Takehiro , Kawashima Toshiyuki , Terakawa Yuzo , Ishibashi Kenichi , Tsuyuguchi Naohiro , Tanoue Yuta , Nagahama Atsufumi , Uda Hiroshi , Koh Saya , Sasaki Tsuyoshi , Ohata Kenji , Kanemura Yonehiro , Goto Takeo
Published: January 2022

This study aimed whether the uptake of amino tracer positron emission tomography (PET) can be used as an additional imaging biomarker to estimate the prognosis of glioma. Participants comprised 56 adult patients with newly diagnosed and untreated World Health Organization (WHO) grade II–IV astrocytic glioma who underwent surgical excision and were evaluated by 11C-methionine PET prior to the surgical excision at Osaka City University Hospital from July 2011 to March 2018. Clinical and imaging studies were retrospectively reviewed based on medical records at our institution. Preoperative Karnofsky Performance Status (KPS) only influenced progression-free survival (hazard ratio [HR] 0.20; 95% confidence interval [CI] 0.10–0.41, p < 0.0001), whereas histology (anaplastic astrocytoma: HR 5.30, 95% CI 1.23–22.8, p = 0.025; glioblastoma: HR 11.52, 95% CI 2.27–58.47, p = 0.0032), preoperative KPS ≥ 80 (HR 0.23, 95% CI 0.09–0.62, p = 0.004), maximum lesion-to-contralateral normal brain tissue (LN max) ≥ 4.03 (HR 0.24, 95% CI 0.08–0.71, p = 0.01), and isocitrate dehydrogenase (IDH) status (HR 14.06, 95% CI 1.81–109.2, p = 0.011) were factors influencing overall survival (OS) in multivariate Cox regression. OS was shorter in patients with LN max ≥ 4.03 (29.3 months) than in patients with LN max < 4.03 (not reached; p = 0.03). OS differed significantly between patients with IDH mutant/LN max < 4.03 and patients with IDH mutant/LN max ≥ 4.03. LN max using 11C-methionine PET may be used in prognostic markers for newly identified and untreated WHO grade II–IV astrocytic glioma.
Discontinuation of Azathioprine could be considered in pediatric patients with Crohn’s disease who have sustained clinical and deep remission
Authors: Jeong Tae Jong , Kim Eun Sil , Kwon Yiyoung , Kim Seonwoo , Seo Sang Won , Choe Yon Ho , Kim Mi Jin
Published: January 2022

Few studies have demonstrated treatment strategies about the duration and cessation of medications in patients with Crohn’s disease (CD). We investigated factors affecting clinical relapse after infliximab (IFX) or azathioprine (AZA) withdrawal in pediatric patients with CD on combination therapy. Pediatric patients with moderate-to-severe CD receiving combination therapy were analyzed retrospectively and factors associated with clinical relapse were investigated. Discontinuation of IFX or AZA was performed in patients who sustained clinical remission (CR) for at least two years and achieved deep remission. A total of 75 patients were included. Forty-four patients (58.7%) continued with combination therapy and 31 patients (41.3%) discontinued AZA or IFX (AZA withdrawal 10, IFX withdrawal 15, both withdrawal 6). Cox proportional-hazards regression and statistical internal validation identified three factors associated with clinical relapse: IFX cessation (hazard ratio; HR 2.982, P = 0.0081), IFX TLs during maintenance therapy (HR 0.581, P = 0.003), 6-thioguanine nucleotide (6-TGN) level (HR 0.978, P < 0.001). However, AZA cessation was not associated with clinical relapse (P = 0.9021). Even when applied in pediatric patients who met stringent criteria, IFX cessation increased the relapse risk. However, withdrawal of AZA could be contemplated in pediatric patients with CD who have sustained CR for at least 2 years and achieved deep remission.