bluuebunny/crossref_metadata_2025_split huggingface dataset:
1,4-dihydroxy quininib activates ferroptosis pathways in metastatic uveal melanoma and reveals a novel prognostic biomarker signature
Authors: Tonelotto Valentina , Costa-Garcia Marcel , O’Reilly Eve , Smith Kaelin Francis , Slater Kayleigh , Dillon Eugene T. , Pendino Marzia , Higgins Catherine , Sist Paola , Bosch Rosa , Passamonti Sabina , Piulats Josep M. , Villanueva Alberto , Tramer Federica , Vanella Luca , Carey Michelle , Kennedy Breandán N. 
Published: February 2024

AbstractUveal melanoma (UM) is an ocular cancer, with propensity for lethal liver metastases. When metastatic UM (MUM) occurs, as few as 8% of patients survive beyond two years. Efficacious treatments for MUM are urgently needed. 1,4-dihydroxy quininib, a cysteinyl leukotriene receptor 1 (CysLT1) antagonist, alters UM cancer hallmarks in vitro, ex vivo and in vivo. Here, we investigated the 1,4-dihydroxy quininib mechanism of action and its translational potential in MUM. Proteomic profiling of OMM2.5 cells identified proteins differentially expressed after 1,4-dihydroxy quininib treatment. Glutathione peroxidase 4 (GPX4), glutamate-cysteine ligase modifier subunit (GCLM), heme oxygenase 1 (HO-1) and 4 hydroxynonenal (4-HNE) expression were assessed by immunoblots. Biliverdin, glutathione and lipid hydroperoxide were measured biochemically. Association between the expression of a specific ferroptosis signature and UM patient survival was performed using public databases. Our data revealed that 1,4-dihydroxy quininib modulates the expression of ferroptosis markers in OMM2.5 cells. Biochemical assays validated that GPX4, biliverdin, GCLM, glutathione and lipid hydroperoxide were significantly altered. HO-1 and 4-HNE levels were significantly increased in MUM tumor explants from orthotopic patient-derived xenografts (OPDX). Expression of genes inhibiting ferroptosis is significantly increased in UM patients with chromosome 3 monosomy. We identified IFerr, a novel ferroptosis signature correlating with UM patient survival. Altogether, we demontrated that in MUM cells and tissues, 1,4-dihydroxy quininib modulates key markers that induce ferroptosis, a relatively new type of cell death driven by iron-dependent peroxidation of phospholipids. Furthermore, we showed that high expression of specific genes inhibiting ferroptosis is associated with a worse UM prognosis, thus, the IFerr signature is a potential prognosticator for which patients develop MUM. All in all, ferroptosis has potential as a clinical biomarker and therapeutic target for MUM.
The dynamic genetic determinants of increased transcriptional divergence in spermatids
Authors: Panten Jasper , Heinen Tobias , Ernst Christina , Eling Nils , Wagner Rebecca E. , Satorius Maja , Marioni John C. , Stegle Oliver , Odom Duncan T. 
Published: February 2024

AbstractCis-genetic effects are key determinants of transcriptional divergence in discrete tissues and cell types. However, how cis- and trans-effects act across continuous trajectories of cellular differentiation in vivo is poorly understood. Here, we quantify allele-specific expression during spermatogenic differentiation at single-cell resolution in an F1 hybrid mouse system, allowing for the comprehensive characterisation of cis- and trans-genetic effects, including their dynamics across cellular differentiation. Collectively, almost half of the genes subject to genetic regulation show evidence for dynamic cis-effects that vary during differentiation. Our system also allows us to robustly identify dynamic trans-effects, which are less pervasive than cis-effects. In aggregate, genetic effects were strongest in round spermatids, which parallels their increased transcriptional divergence we identified between species. Our approach provides a comprehensive quantification of the variability of genetic effects in vivo, and demonstrates a widely applicable strategy to dissect the impact of regulatory variants on gene regulation in dynamic systems.
Unified picture of vibrational relaxation of OH stretch at the air/water interface
Authors: Sung Woongmo , Inoue Ken-ichi , Nihonyanagi Satoshi , Tahara Tahei 
Published: February 2024

AbstractThe elucidation of the energy dissipation process is crucial for understanding various phenomena occurring in nature. Yet, the vibrational relaxation and its timescale at the water interface, where the hydrogen-bonding network is truncated, are not well understood and are still under debate. In the present study, we focus on the OH stretch of interfacial water at the air/water interface and investigate its vibrational relaxation by femtosecond time-resolved, heterodyne-detected vibrational sum-frequency generation (TR-HD-VSFG) spectroscopy. The temporal change of the vibrationally excited hydrogen-bonded (HB) OH stretch band (ν=1→2 transition) is measured, enabling us to determine reliable vibrational relaxation (T1) time. The T1 times obtained with direct excitations of HB OH stretch are 0.2-0.4 ps, which are similar to the T1 time in bulk water and do not noticeably change with the excitation frequency. It suggests that vibrational relaxation of the interfacial HB OH proceeds predominantly with the intramolecular relaxation mechanism as in the case of bulk water. The delayed rise and following decay of the excited-state HB OH band are observed with excitation of free OH stretch, indicating conversion from excited free OH to excited HB OH (~0.9 ps) followed by relaxation to low-frequency vibrations (~0.3 ps). This study provides a complete set of the T1 time of the interfacial OH stretch and presents a unified picture of its vibrational relaxation at the air/water interface.
Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage
Authors: Ruz-Maldonado Inmaculada , Gonzalez John T. , Zhang Hanming , Sun Jonathan , Bort Alicia , Kabir Inamul , Kibbey Richard G. , Suárez Yajaira , Greif Daniel M. , Fernández-Hernando Carlos 
Published: February 2024

AbstractMidlobular hepatocytes are proposed to be the most plastic hepatic cell, providing a reservoir for hepatocyte proliferation during homeostasis and regeneration. However, other mechanisms beyond hyperplasia have been little explored and the contribution of other hepatocyte subpopulations to regeneration has been controversial. Thus, re-examining hepatocyte dynamics during regeneration is critical for cell therapy and treatment of liver diseases. Using a mouse model of hepatocyte- and non-hepatocyte- multicolor lineage tracing, we demonstrate that midlobular hepatocytes also undergo hypertrophy in response to chemical, physical, and viral insults. Our study shows that this subpopulation also combats liver impairment after infection with coronavirus. Furthermore, we demonstrate that pericentral hepatocytes also expand in number and size during the repair process and Galectin-9-CD44 pathway may be critical for driving these processes. Notably, we also identified that transdifferentiation and cell fusion during regeneration after severe injury contribute to recover hepatic function.
Tailoring tokamak error fields to control plasma instabilities and transport
Authors: Yang SeongMoo , Park Jong-Kyu , Jeon YoungMu , Logan Nikolas C. , Lee Jaehyun , Hu Qiming , Lee JongHa , Kim SangKyeun , Kim Jaewook , Lee Hyungho , Na Yong-Su , Hahm Taik Soo , Choi Gyungjin , Snipes Joseph A. , Park Gunyoung , Ko Won-Ha 
Published: February 2024

AbstractA tokamak relies on the axisymmetric magnetic fields to confine fusion plasmas and aims to deliver sustainable and clean energy. However, misalignments arise inevitably in the tokamak construction, leading to small asymmetries in the magnetic field known as error fields (EFs). The EFs have been a major concern in the tokamak approaches because small EFs, even less than 0.1%, can drive a plasma disruption. Meanwhile, the EFs in the tokamak can be favorably used for controlling plasma instabilities, such as edge-localized modes (ELMs). Here we show an optimization that tailors the EFs to maintain an edge 3D response for ELM control with a minimized core 3D response to avoid plasma disruption and unnecessary confinement degradation. We design and demonstrate such an edge-localized 3D response in the KSTAR facility, benefiting from its unique flexibility to change many degrees of freedom in the 3D coil space for the various fusion plasma regimes. This favorable control of the tokamak EF represents a notable advance for designing intrinsically 3D tokamaks to optimize stability and confinement for next-step fusion reactors.
Robust links in photoactive covalent organic frameworks enable effective photocatalytic reactions under harsh conditions
Authors: Wang Jia-Rui , Song Kepeng , Luan Tian-Xiang , Cheng Ke , Wang Qiurong , Wang Yue , Yu William W. , Li Pei-Zhou , Zhao Yanli 
Published: February 2024

AbstractDeveloping heterogeneous photocatalysts for the applications in harsh conditions is of high importance but challenging. Herein, by converting the imine linkages into quinoline groups of triphenylamine incorporated covalent organic frameworks (COFs), two photosensitive COFs, namely TFPA-TAPT-COF-Q and TFPA-TPB-COF-Q, are successfully constructed. The obtained quinoline-linked COFs display improved stability and photocatalytic activity, making them suitable photocatalysts for photocatalytic reactions under harsh conditions, as verified by the recyclable photocatalytic reactions of organic acid involving oxidative decarboxylation and organic base involving benzylamine coupling. Under strong oxidative condition, the quinoline-linked COFs show a high efficiency up to 11831.6 μmol·g−1·h−1 and a long-term recyclable usability for photocatalytic production of H2O2, while the pristine imine-linked COFs are less catalytically active and easily decomposed in these harsh conditions. The results demonstrate that enhancing the linkage robustness of photoactive COFs is a promising strategy to construct heterogeneous catalysts for photocatalytic reactions under harsh conditions.
Sustainable conversion of alkaline nitrate to ammonia at activities greater than 2 A cm−2
Authors: Liao Wanru , Wang Jun , Ni Ganghai , Liu Kang , Liu Changxu , Chen Shanyong , Wang Qiyou , Chen Yingkang , Luo Tao , Wang Xiqing , Wang Yanqiu , Li Wenzhang , Chan Ting-Shan , Ma Chao , Li Hongmei , Liang Ying , Liu Weizhen , Fu Junwei , Xi Beidou , Liu Min 
Published: February 2024

AbstractNitrate (NO3‒) pollution poses significant threats to water quality and global nitrogen cycles. Alkaline electrocatalytic NO3‒ reduction reaction (NO3RR) emerges as an attractive route for enabling NO3‒ removal and sustainable ammonia (NH3) synthesis. However, it suffers from insufficient proton (H+) supply in high pH conditions, restricting NO3‒-to-NH3 activity. Herein, we propose a halogen-mediated H+ feeding strategy to enhance the alkaline NO3RR performance. Our platform achieves near-100% NH3 Faradaic efficiency (pH = 14) with a current density of 2 A cm–2 and enables an over 99% NO3–-to-NH3 conversion efficiency. We also convert NO3‒ to high-purity NH4Cl with near-unity efficiency, suggesting a practical approach to valorizing pollutants into valuable ammonia products. Theoretical simulations and in situ experiments reveal that Cl-coordination endows a shifted d-band center of Pd atoms to construct local H+-abundant environments, through arousing dangling O-H water dissociation and fast *H desorption, for *NO intermediate hydrogenation and finally effective NO3‒-to-NH3 conversion.
Structural role for DNA Ligase IV in promoting the fidelity of non-homologous end joining
Authors: Stinson Benjamin M. , Carney Sean M. , Walter Johannes C. , Loparo Joseph J. 
Published: February 2024

AbstractNonhomologous end joining (NHEJ), the primary pathway of vertebrate DNA double-strand-break (DSB) repair, directly re-ligates broken DNA ends. Damaged DSB ends that cannot be immediately re-ligated are modified by NHEJ processing enzymes, including error-prone polymerases and nucleases, to enable ligation. However, DSB ends that are initially compatible for re-ligation are typically joined without end processing. As both ligation and end processing occur in the short-range (SR) synaptic complex that closely aligns DNA ends, it remains unclear how ligation of compatible ends is prioritized over end processing. In this study, we identify structural interactions of the NHEJ-specific DNA Ligase IV (Lig4) within the SR complex that prioritize ligation and promote NHEJ fidelity. Mutational analysis demonstrates that Lig4 must bind DNA ends to form the SR complex. Furthermore, single-molecule experiments show that a single Lig4 binds both DNA ends at the instant of SR synapsis. Thus, Lig4 is poised to ligate compatible ends upon initial formation of the SR complex before error-prone processing. Our results provide a molecular basis for the fidelity of NHEJ.
Intercellular transfer of cancer cell invasiveness via endosome-mediated protease shedding
Authors: Wenzel Eva Maria , Pedersen Nina Marie , Elfmark Liv Anker , Wang Ling , Kjos Ingrid , Stang Espen , Malerød Lene , Brech Andreas , Stenmark Harald , Raiborg Camilla 
Published: February 2024

AbstractOverexpression of the transmembrane matrix metalloproteinase MT1-MMP/MMP14 promotes cancer cell invasion. Here we show that MT1-MMP-positive cancer cells turn MT1-MMP-negative cells invasive by transferring a soluble catalytic ectodomain of MT1-MMP. Surprisingly, this effect depends on the presence of TKS4 and TKS5 in the donor cell, adaptor proteins previously implicated in invadopodia formation. In endosomes of the donor cell, TKS4/5 promote ADAM-mediated cleavage of MT1-MMP by bridging the two proteases, and cleavage is stimulated by the low intraluminal pH of endosomes. The bridging depends on the PX domains of TKS4/5, which coincidently interact with the cytosolic tail of MT1-MMP and endosomal phosphatidylinositol 3-phosphate. MT1-MMP recruits TKS4/5 into multivesicular endosomes for their subsequent co-secretion in extracellular vesicles, together with the enzymatically active ectodomain. The shed ectodomain converts non-invasive recipient cells into an invasive phenotype. Thus, TKS4/5 promote intercellular transfer of cancer cell invasiveness by facilitating ADAM-mediated shedding of MT1-MMP in acidic endosomes.
Regression-based Deep-Learning predicts molecular biomarkers from pathology slides
Authors: El Nahhas Omar S. M. , Loeffler Chiara M. L. , Carrero Zunamys I. , van Treeck Marko , Kolbinger Fiona R. , Hewitt Katherine J. , Muti Hannah S. , Graziani Mara , Zeng Qinghe , Calderaro Julien , Ortiz-Brüchle Nadina , Yuan Tanwei , Hoffmeister Michael , Brenner Hermann , Brobeil Alexander , Reis-Filho Jorge S. , Kather Jakob Nikolas 
Published: February 2024

AbstractDeep Learning (DL) can predict biomarkers from cancer histopathology. Several clinically approved applications use this technology. Most approaches, however, predict categorical labels, whereas biomarkers are often continuous measurements. We hypothesize that regression-based DL outperforms classification-based DL. Therefore, we develop and evaluate a self-supervised attention-based weakly supervised regression method that predicts continuous biomarkers directly from 11,671 images of patients across nine cancer types. We test our method for multiple clinically and biologically relevant biomarkers: homologous recombination deficiency score, a clinically used pan-cancer biomarker, as well as markers of key biological processes in the tumor microenvironment. Using regression significantly enhances the accuracy of biomarker prediction, while also improving the predictions’ correspondence to regions of known clinical relevance over classification. In a large cohort of colorectal cancer patients, regression-based prediction scores provide a higher prognostic value than classification-based scores. Our open-source regression approach offers a promising alternative for continuous biomarker analysis in computational pathology.
Diffusive kinks turn kirigami into machines
Authors: Janbaz Shahram , Coulais Corentin 
Published: February 2024

AbstractKinks define boundaries between distinct configurations of a material. In the context of mechanical metamaterials, kinks have recently been shown to underpin logic, shape-changing and locomotion functionalities. So far such kinks propagate by virtue of inertia or of an external load. Here, we discover the emergence of propagating kinks in purely dissipative kirigami. To this end, we create kirigami that shape-change into different textures depending on how fast they are stretched. We find that if we stretch fast and wait, the viscoelastic kirigami can eventually snap from one texture to another. Crucially, such a snapping instability occurs in a sequence and a propagating diffusive kink emerges. As such, it mimics the slow sequential folding observed in biological systems, e.g., Mimosa Pudica. We finally demonstrate that diffusive kinks can be harnessed for basic machine-like functionalities, such as sensing, dynamic shape morphing, transport and manipulation of objects.
Nutrient-dependent regulation of a stable intron modulates germline mitochondrial quality control
Authors: Ng Annabel Qi En , Chan Seow Neng , Pek Jun Wei 
Published: February 2024

AbstractMitochondria are inherited exclusively from the mothers and are required for the proper development of embryos. Hence, germline mitochondrial quality is highly regulated during oogenesis to ensure oocyte viability. How nutrient availability influences germline mitochondrial quality control is unclear. Here we find that fasting leads to the accumulation of mitochondrial clumps and oogenesis arrest inDrosophila. Fasting induces the downregulation of the DIP1-Clueless pathway, leading to an increase in the expression of a stable intronic sequence RNA calledsisR-1. Mechanistically,sisR-1localizes to the mitochondrial clumps to inhibit the poly-ubiquitination of the outer mitochondrial protein Porin/VDAC1, thereby suppressing p62-mediated mitophagy. Alleviation of the fasting-induced highsisR-1levels by eithersisR-1RNAi or refeeding leads to mitophagy, the resumption of oogenesis and an improvement in oocyte quality. Thus, our study provides a possible mechanism by which fasting can improve oocyte quality by modulating the mitochondrial quality control pathway. Of note, we uncover that thesisR-1response also regulates mitochondrial clumping and oogenesis during protein deprivation, heat shock and aging, suggesting a broader role for this mechanism in germline mitochondrial quality control.
Pick-up single-cell proteomic analysis for quantifying up to 3000 proteins in a Mammalian cell
Authors: Wang Yu , Guan Zhi-Ying , Shi Shao-Wen , Jiang Yi-Rong , Zhang Jie , Yang Yi , Wu Qiong , Wu Jie , Chen Jian-Bo , Ying Wei-Xin , Xu Qin-Qin , Fan Qian-Xi , Wang Hui-Feng , Zhou Li , Wang Ling , Fang Jin , Pan Jian-Zhang , Fang Qun 
Published: February 2024

AbstractThe shotgun proteomic analysis is currently the most promising single-cell protein sequencing technology, however its identification level of ~1000 proteins per cell is still insufficient for practical applications. Here, we develop a pick-up single-cell proteomic analysis (PiSPA) workflow to achieve a deep identification capable of quantifying up to 3000 protein groups in a mammalian cell using the label-free quantitative method. The PiSPA workflow is specially established for single-cell samples mainly based on a nanoliter-scale microfluidic liquid handling robot, capable of achieving single-cell capture, pretreatment and injection under the pick-up operation strategy. Using this customized workflow with remarkable improvement in protein identification, 2449–3500, 2278–3257 and 1621–2904 protein groups are quantified in single A549 cells (n = 37), HeLa cells (n = 44) and U2OS cells (n = 27) under the DIA (MBR) mode, respectively. Benefiting from the flexible cell picking-up ability, we study HeLa cell migration at the single cell proteome level, demonstrating the potential in practical biological research from single-cell insight.
Eco-evolutionary dynamics of gut phageome in wild gibbons (Hoolock tianxing) with seasonal diet variations
Authors: Gao Shao-Ming , Fei Han-Lan , Li Qi , Lan Li-Ying , Huang Li-Nan , Fan Peng-Fei 
Published: February 2024

AbstractIt has been extensively studied that the gut microbiome provides animals flexibility to adapt to food variability. Yet, how gut phageome responds to diet variation of wild animals remains unexplored. Here, we analyze the eco-evolutionary dynamics of gut phageome in six wild gibbons (Hoolock tianxing) by collecting individually-resolved fresh fecal samples and parallel feeding behavior data for 15 consecutive months. Application of complementary viral and microbial metagenomics recovers 39,198 virulent and temperate phage genomes from the feces. Hierarchical cluster analyses show remarkable seasonal diet variations in gibbons. From high-fruit to high-leaf feeding period, the abundances of phage populations are seasonally fluctuated, especially driven by the increased abundance of virulent phages that kill the Lachnospiraceae hosts, and a decreased abundance of temperate phages that piggyback the Bacteroidaceae hosts. Functional profiling reveals an enrichment through horizontal gene transfers of toxin-antitoxin genes on temperate phage genomes in high-leaf season, potentially conferring benefits to their prokaryotic hosts. The phage-host ecological dynamics are driven by the coevolutionary processes which select for tail fiber and DNA primase genes on virulent and temperate phage genomes, respectively. Our results highlight complex phageome-microbiome interactions as a key feature of the gibbon gut microbial ecosystem responding to the seasonal diet.
High intrinsic phase stability of ultrathin 2M WS2
Authors: Liu Xiangye , Zhang Pingting , Wang Shiyao , Fang Yuqiang , Wu Penghui , Xiang Yue , Chen Jipeng , Zhao Chendong , Zhang Xian , Zhao Wei , Wang Junjie , Huang Fuqiang , Guan Cao 
Published: February 2024

AbstractMetallic 2M or 1T′-phase transition metal dichalcogenides (TMDs) attract increasing interests owing to their fascinating physicochemical properties, such as superconductivity, optical nonlinearity, and enhanced electrochemical activity. However, these TMDs are metastable and tend to transform to the thermodynamically stable 2H phase. In this study, through systematic investigation and theoretical simulation of phase change of 2M WS2, we demonstrate that ultrathin 2M WS2 has significantly higher intrinsic thermal stabilities than the bulk counterparts. The 2M-to-2H phase transition temperature increases from 120 °C to 210 °C in the air as thickness of WS2 is reduced from bulk to bilayer. Monolayered 1T′ WS2 can withstand temperatures up to 350 °C in the air before being oxidized, and up to 450 °C in argon atmosphere before transforming to 1H phase. The higher stability of thinner 2M WS2 is attributed to stiffened intralayer bonds, enhanced thermal conductivity and higher average barrier per layer during the layer(s)-by-layer(s) phase transition process. The observed high intrinsic phase stability can expand the practical applications of ultrathin 2M TMDs.