bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annexin A2 combined with TTK accelerates esophageal cancer progression via the Akt/mTOR signaling pathway
Authors: Liu Ruiqi , Lu Yanwei , Li Jing , Yao Weiping , Wu Jiajun , Chen Xiaoyan , Huang Luanluan , Nan Ding , Zhang Yitian , Chen Weijun , Wang Ying , Jia Yongshi , Tang Jianming , Liang Xiaodong , Zhang Haibo 
Published: April 2024

AbstractAnnexin A2 (ANXA2) is a widely reported oncogene. However, the mechanism of ANXA2 in esophageal cancer is not fully understood. In this study, we provided evidence that ANXA2 promotes the progression of esophageal squamous cell carcinoma (ESCC) through the downstream target threonine tyrosine kinase (TTK). These results are consistent with the up-regulation of ANXA2 and TTK in ESCC. In vitro experiments by knockdown and overexpression of ANXA2 revealed that ANXA2 promotes the progression of ESCC by enhancing cancer cell proliferation, migration, and invasion. Subsequently, animal models also confirmed the role of ANXA2 in promoting the proliferation and metastasis of ESCC. Mechanistically, the ANXA2/TTK complex activates the Akt/mTOR signaling pathway and accelerates epithelial-mesenchymal transition (EMT), thereby promoting the invasion and metastasis of ESCC. Furthermore, we identified that TTK overexpression can reverse the inhibition of ESCC invasion after ANXA2 knockdown. Overall, these data indicate that the combination of ANXA2 and TTK regulates the activation of the Akt/mTOR pathway and accelerates the progression of ESCC. Therefore, the ANXA2/TTK/Akt/mTOR axis is a potential therapeutic target for ESCC.
TANGO1 inhibitors reduce collagen secretion and limit tissue scarring
Authors: Raote Ishier , Rosendahl Ann-Helen , Häkkinen Hanna-Maria , Vibe Carina , Küçükaylak Ismail , Sawant Mugdha , Keufgens Lena , Frommelt Pia , Halwas Kai , Broadbent Katrina , Cunquero Marina , Castro Gustavo , Villemeur Marie , Nüchel Julian , Bornikoel Anna , Dam Binita , Zirmire Ravindra K. , Kiran Ravi , Carolis Carlo , Andilla Jordi , Loza-Alvarez Pablo , Ruprecht Verena , Jamora Colin , Campelo Felix , Krüger Marcus , Hammerschmidt Matthias , Eckes Beate , Neundorf Ines , Krieg Thomas , Malhotra Vivek 
Published: April 2024

AbstractUncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts. We have designed membrane permeant peptide inhibitors that specifically target the primary interface between TANGO1 and cTAGE5, an interaction that is required for collagen export from endoplasmic reticulum exit sites (ERES). Application of the peptide inhibitors leads to reduced TANGO1 and cTAGE5 protein levels and a corresponding inhibition in the secretion of several ECM components, including collagens. Peptide inhibitor treatment in zebrafish results in altered tissue architecture and reduced granulation tissue formation during cutaneous wound healing. The inhibitors reduce secretion of several ECM proteins, including collagens, fibrillin and fibronectin in human dermal fibroblasts and in cells obtained from patients with a generalized fibrotic disease (scleroderma). Taken together, targeted interference of the TANGO1-cTAGE5 binding interface could enable therapeutic modulation of ERES function in ECM hypersecretion, during wound healing and fibrotic processes.
Emergence of enhancers at late DNA replicating regions
Authors: Cornejo-Páramo Paola , Petrova Veronika , Zhang Xuan , Young Robert S. , Wong Emily S. 
Published: April 2024

AbstractEnhancers are fast-evolving genomic sequences that control spatiotemporal gene expression patterns. By examining enhancer turnover across mammalian species and in multiple tissue types, we uncover a relationship between the emergence of enhancers and genome organization as a function of germline DNA replication time. While enhancers are most abundant in euchromatic regions, enhancers emerge almost twice as often in late compared to early germline replicating regions, independent of transposable elements. Using a deep learning sequence model, we demonstrate that new enhancers are enriched for mutations that alter transcription factor (TF) binding. Recently evolved enhancers appear to be mostly neutrally evolving and enriched in eQTLs. They also show more tissue specificity than conserved enhancers, and the TFs that bind to these elements, as inferred by binding sequences, also show increased tissue-specific gene expression. We find a similar relationship with DNA replication time in cancer, suggesting that these observations may be time-invariant principles of genome evolution. Our work underscores that genome organization has a profound impact in shaping mammalian gene regulation.
A comprehensive synthetic library of poly-N-acetyl glucosamines enabled vaccine against lethal challenges of Staphylococcus aureus
Authors: Tan Zibin , Yang Weizhun , O’Brien Nicholas A. , Pan Xingling , Ramadan Sherif , Marsh Terence , Hammer Neal , Cywes-Bentley Colette , Vinacur Mariana , Pier Gerald B. , Gildersleeve Jeffrey C. , Huang Xuefei 
Published: April 2024

AbstractPoly-β-(1–6)-N-acetylglucosamine (PNAG) is an important vaccine target, expressed on many pathogens. A critical hurdle in developing PNAG based vaccine is that the impacts of the number and the position of free amine vs N-acetylation on its antigenicity are not well understood. In this work, a divergent strategy is developed to synthesize a comprehensive library of 32 PNAG pentasaccharides. This library enables the identification of PNAG sequences with specific patterns of free amines as epitopes for vaccines against Staphylococcus aureus (S. aureus), an important human pathogen. Active vaccination with the conjugate of discovered PNAG epitope with mutant bacteriophage Qβ as a vaccine carrier as well as passive vaccination with diluted rabbit antisera provides mice with near complete protection against infections by S. aureus including methicillin-resistant S. aureus (MRSA). Thus, the comprehensive PNAG pentasaccharide library is an exciting tool to empower the design of next generation vaccines.
Transparent integrated pyroelectric-photovoltaic structure for photo-thermo hybrid power generation
Authors: Patel Malkeshkumar , Park Hyeong-Ho , Bhatnagar Priyanka , Kumar Naveen , Lee Junsik , Kim Joondong 
Published: April 2024

AbstractThermal losses in photoelectric devices limit their energy conversion efficiency, and cyclic input of energy coupled with pyroelectricity can overcome this limit. Here, incorporating a pyroelectric absorber into a photovoltaic heterostructure device enables efficient electricity generation by leveraging spontaneous polarization based on pulsed light-induced thermal changes. The proposed pyroelectric-photovoltaic device outperforms traditional photovoltaic devices by 2.5 times due to the long-range electric field that occurs under pulse illumination. Optimization of parameters such as pulse frequency, scan speed, and illumination wavelength enhances power harvesting, as demonstrated by a power conversion efficiency of 11.9% and an incident-photon-to-current conversion efficiency of 200% under optimized conditions. This breakthrough enables reconfigurable electrostatic devices and presents an opportunity to accelerate technology that surpasses conventional limits in energy generation.
Wild-type IDH2 is a therapeutic target for triple-negative breast cancer
Authors: Li Jiang-jiang , Yu Tiantian , Zeng Peiting , Tian Jingyu , Liu Panpan , Qiao Shuang , Wen Shijun , Hu Yumin , Liu Qiao , Lu Wenhua , Zhang Hui , Huang Peng 
Published: April 2024

AbstractMutations in isocitrate dehydrogenases (IDH) are oncogenic events due to the generation of oncogenic metabolite 2-hydroxyglutarate. However, the role of wild-type IDH in cancer development remains elusive. Here we show that wild-type IDH2 is highly expressed in triple negative breast cancer (TNBC) cells and promotes their proliferation in vitro and tumor growth in vivo. Genetic silencing or pharmacological inhibition of wt-IDH2 causes a significant increase in α-ketoglutarate (α-KG), indicating a suppression of reductive tricarboxylic acid (TCA) cycle. The aberrant accumulation of α-KG due to IDH2 abrogation inhibits mitochondrial ATP synthesis and promotes HIF-1α degradation, leading to suppression of glycolysis. Such metabolic double-hit results in ATP depletion and suppression of tumor growth, and renders TNBC cells more sensitive to doxorubicin treatment. Our study reveals a metabolic property of TNBC cells with active utilization of glutamine via reductive TCA metabolism, and suggests that wild-type IDH2 plays an important role in this metabolic process and could be a potential therapeutic target for TNBC.
Visualized in-sensor computing
Authors: Ni Yao , Liu Jiaqi , Han Hong , Yu Qianbo , Yang Lu , Xu Zhipeng , Jiang Chengpeng , Liu Lu , Xu Wentao 
Published: April 2024

AbstractIn artificial nervous systems, conductivity changes indicate synaptic weight updates, but they provide limited information compared to living organisms. We present the pioneering design and production of an electrochromic neuromorphic transistor employing color updates to represent synaptic weight for in-sensor computing. Here, we engineer a specialized mechanism for adaptively regulating ion doping through an ion-exchange membrane, enabling precise control over color-coded synaptic weight, an unprecedented achievement. The electrochromic neuromorphic transistor not only enhances electrochromatic capabilities for hardware coding but also establishes a visualized pattern-recognition network. Integrating the electrochromic neuromorphic transistor with an artificial whisker, we simulate a bionic reflex system inspired by the longicorn beetle, achieving real-time visualization of signal flow within the reflex arc in response to environmental stimuli. This research holds promise in extending the biomimetic coding paradigm and advancing the development of bio-hybrid interfaces, particularly in incorporating color-based expressions.
Functionalized MXene ink enables environmentally stable printed electronics
Authors: Ko Tae Yun , Ye Heqing , Murali G. , Lee Seul-Yi , Park Young Ho , Lee Jihoon , Lee Juyun , Yun Dong-Jin , Gogotsi Yury , Kim Seon Joon , Kim Se Hyun , Jeong Yong Jin , Park Soo-Jin , In Insik 
Published: April 2024

AbstractEstablishing dependable, cost-effective electrical connections is vital for enhancing device performance and shrinking electronic circuits. MXenes, combining excellent electrical conductivity, high breakdown voltage, solution processability, and two-dimensional morphology, are promising candidates for contacts in microelectronics. However, their hydrophilic surfaces, which enable spontaneous environmental degradation and poor dispersion stability in organic solvents, have restricted certain electronic applications. Herein, electrohydrodynamic printing technique is used to fabricate fully solution-processed thin-film transistors with alkylated 3,4-dihydroxy-L-phenylalanine functionalized Ti3C2Tx (AD-MXene) as source, drain, and gate electrodes. The AD-MXene has excellent dispersion stability in ethanol, which is required for electrohydrodynamic printing, and maintains high electrical conductivity. It outperformed conventional vacuum-deposited Au and Al electrodes, providing thin-film transistors with good environmental stability due to its hydrophobicity. Further, thin-film transistors are integrated into logic gates and one-transistor-one-memory cells. This work, unveiling the ligand-functionalized MXenes’ potential in printed electrical contacts, promotes environmentally robust MXene-based electronics (MXetronics).
Altered grid-like coding in early blind people
Authors: Sigismondi Federica , Xu Yangwen , Silvestri Mattia , Bottini Roberto 
Published: April 2024

AbstractCognitive maps in the hippocampal-entorhinal system are central for the representation of both spatial and non-spatial relationships. Although this system, especially in humans, heavily relies on vision, the role of visual experience in shaping the development of cognitive maps remains largely unknown. Here, we test sighted and early blind individuals in both imagined navigation in fMRI and real-world navigation. During imagined navigation, the Human Navigation Network, constituted by frontal, medial temporal, and parietal cortices, is reliably activated in both groups, showing resilience to visual deprivation. However, neural geometry analyses highlight crucial differences between groups. A 60° rotational symmetry, characteristic of a hexagonal grid-like coding, emerges in the entorhinal cortex of sighted but not blind people, who instead show a 90° (4-fold) symmetry, indicative of a square grid. Moreover, higher parietal cortex activity during navigation in blind people correlates with the magnitude of 4-fold symmetry. In sum, early blindness can alter the geometry of entorhinal cognitive maps, possibly as a consequence of higher reliance on parietal egocentric coding during navigation.
CoCas9 is a compact nuclease from the human microbiome for efficient and precise genome editing
Authors: Pedrazzoli Eleonora , Demozzi Michele , Visentin Elisabetta , Ciciani Matteo , Bonuzzi Ilaria , Pezzè Laura , Lucchetta Lorenzo , Maule Giulia , Amistadi Simone , Esposito Federica , Lupo Mariangela , Miccio Annarita , Auricchio Alberto , Casini Antonio , Segata Nicola , Cereseto Anna 
Published: April 2024

AbstractThe expansion of the CRISPR-Cas toolbox is highly needed to accelerate the development of therapies for genetic diseases. Here, through the interrogation of a massively expanded repository of metagenome-assembled genomes, mostly from human microbiomes, we uncover a large variety (n = 17,173) of type II CRISPR-Cas loci. Among these we identify CoCas9, a strongly active and high-fidelity nuclease with reduced molecular size (1004 amino acids) isolated from an uncultivated Collinsella species. CoCas9 is efficiently co-delivered with its sgRNA through adeno associated viral (AAV) vectors, obtaining efficient in vivo editing in the mouse retina. With this study we uncover a collection of previously uncharacterized Cas9 nucleases, including CoCas9, which enriches the genome editing toolbox.
MYADM binds human parechovirus 1 and is essential for viral entry
Authors: Qiao Wenjie , Richards Christopher M. , Kim Youlim , Zengel James R. , Ding Siyuan , Greenberg Harry B. , Carette Jan E. 
Published: April 2024

AbstractHuman parechoviruses (PeV-A) are increasingly being recognized as a cause of infection in neonates and young infants, leading to a spectrum of clinical manifestations ranging from mild gastrointestinal and respiratory illnesses to severe sepsis and meningitis. However, the host factors required for parechovirus entry and infection remain poorly characterized. Here, using genome-wide CRISPR/Cas9 loss-of-function screens, we identify myeloid-associated differentiation marker (MYADM) as a host factor essential for the entry of several human parechovirus genotypes including PeV-A1, PeV-A2 and PeV-A3. Genetic knockout of MYADM confers resistance to PeV-A infection in cell lines and in human gastrointestinal epithelial organoids. Using immunoprecipitation, we show that MYADM binds to PeV-A1 particles via its fourth extracellular loop, and we identify critical amino acid residues within the loop that mediate binding and infection. The demonstrated interaction between MYADM and PeV-A1, and its importance specifically for viral entry, suggest that MYADM is a virus receptor. Knockout of MYADM does not reduce PeV-A1 attachment to cells pointing to a role at the post-attachment stage. Our study suggests that MYADM is a multi-genotype receptor for human parechoviruses with potential as an antiviral target to combat disease associated with emerging parechoviruses.
Metabolic coupling between soil aerobic methanotrophs and denitrifiers in rice paddy fields
Authors: Chen Kang-Hua , Feng Jiao , Bodelier Paul L. E. , Yang Ziming , Huang Qiaoyun , Delgado-Baquerizo Manuel , Cai Peng , Tan Wenfeng , Liu Yu-Rong 
Published: April 2024

AbstractPaddy fields are hotspots of microbial denitrification, which is typically linked to the oxidation of electron donors such as methane (CH4) under anoxic and hypoxic conditions. While several anaerobic methanotrophs can facilitate denitrification intracellularly, whether and how aerobic CH4 oxidation couples with denitrification in hypoxic paddy fields remains virtually unknown. Here we combine a ~3300 km field study across main rice-producing areas of China and 13CH4-DNA-stable isotope probing (SIP) experiments to investigate the role of soil aerobic CH4 oxidation in supporting denitrification. Our results reveal positive relationships between CH4 oxidation and denitrification activities and genes across various climatic regions. Microcosm experiments confirm that CH4 and methanotroph addition promote gene expression involved in denitrification and increase nitrous oxide emissions. Moreover, 13CH4-DNA-SIP analyses identify over 70 phylotypes harboring genes associated with denitrification and assimilating 13C, which are mostly belonged to Rubrivivax, Magnetospirillum, and Bradyrhizobium. Combined analyses of 13C-metagenome-assembled genomes and 13C-metabolomics highlight the importance of intermediates such as acetate, propionate and lactate, released during aerobic CH4 oxidation, for the coupling of CH4 oxidation with denitrification. Our work identifies key microbial taxa and pathways driving coupled aerobic CH4 oxidation and denitrification, with important implications for nitrogen management and greenhouse gas regulation in agroecosystems.
Direct programming of confined surface phonon polariton resonators with the plasmonic phase-change material In3SbTe2
Authors: Conrads Lukas , Schüler Luis , Wirth Konstantin G. , Wuttig Matthias , Taubner Thomas 
Published: April 2024

AbstractTailoring light-matter interaction is essential to realize nanophotonic components. It can be achieved with surface phonon polaritons (SPhPs), an excitation of photons coupled with phonons of polar crystals, which also occur in 2d materials such as hexagonal boron nitride or anisotropic crystals. Ultra-confined resonances are observed by restricting the SPhPs to cavities. Phase-change materials (PCMs) enable non-volatile programming of these cavities based on a change in the refractive index. Recently, the plasmonic PCM In3SbTe2 (IST) was introduced which can be reversibly switched from an amorphous dielectric state to a crystalline metallic one in the entire infrared to realize numerous nanoantenna geometries. However, reconfiguring SPhP resonators to modify the confined polaritons modes remains elusive. Here, we demonstrate direct programming of confined SPhP resonators by phase-switching IST on top of a polar silicon carbide crystal and investigate the strongly confined resonance modes with scanning near-field optical microscopy. Reconfiguring the size of the resonators themselves result in enhanced mode confinements up to a value of $${{{{{\boldsymbol{\lambda }}}}}}{{{{{\boldsymbol{/}}}}}}{{{{{\boldsymbol{35}}}}}}{{{{{\boldsymbol{.}}}}}}$$
λ
/
35
.
Finally, unconventional cavity shapes with complex field patterns are explored as well. This study is a first step towards rapid prototyping of reconfigurable SPhP resonators that can be easily transferred to hyperbolic and anisotropic 2d materials.
The phosphorylation of carboxyl-terminal eIF2α by SPA kinases contributes to enhanced translation efficiency during photomorphogenesis
Authors: Chang Hui-Hsien , Huang Lin-Chen , Browning Karen S. , Huq Enamul , Cheng Mei-Chun 
Published: April 2024

AbstractLight triggers an enhancement of global translation during photomorphogenesis in Arabidopsis, but little is known about the underlying mechanisms. The phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α) at a conserved serine residue in the N-terminus has been shown as an important mechanism for the regulation of protein synthesis in mammalian and yeast cells. However, whether the phosphorylation of this residue in plant eIF2α plays a role in regulation of translation remains elusive. Here, we show that the quadruple mutant of SUPPRESSOR OF PHYA-105 family members (SPA1-SPA4) display repressed translation efficiency after light illumination. Moreover, SPA1 directly phosphorylates the eIF2α C-terminus under light conditions. The C-term-phosphorylated eIF2α promotes translation efficiency and photomorphogenesis, whereas the C-term-unphosphorylated eIF2α results in a decreased translation efficiency. We also demonstrate that the phosphorylated eIF2α enhances ternary complex assembly by promoting its affinity to eIF2β and eIF2γ. This study reveals a unique mechanism by which light promotes translation via SPA1-mediated phosphorylation of the C-terminus of eIF2α in plants.
Single cell tracing of Pomc neurons reveals recruitment of ‘Ghost’ subtypes with atypical identity in a mouse model of obesity
Authors: Leon Stéphane , Simon Vincent , Lee Thomas H. , Steuernagel Lukas , Clark Samantha , Biglari Nasim , Lesté-Lasserre Thierry , Dupuy Nathalie , Cannich Astrid , Bellocchio Luigi , Zizzari Philippe , Allard Camille , Gonzales Delphine , Le Feuvre Yves , Lhuillier Emeline , Brochard Alexandre , Nicolas Jean Charles , Teillon Jérémie , Nikolski Macha , Marsicano Giovanni , Fioramonti Xavier , Brüning Jens C. , Cota Daniela , Quarta Carmelo 
Published: April 2024

AbstractThe hypothalamus contains a remarkable diversity of neurons that orchestrate behavioural and metabolic outputs in a highly plastic manner. Neuronal diversity is key to enabling hypothalamic functions and, according to the neuroscience dogma, it is predetermined during embryonic life. Here, by combining lineage tracing of hypothalamic pro-opiomelanocortin (Pomc) neurons with single-cell profiling approaches in adult male mice, we uncovered subpopulations of ‘Ghost’ neurons endowed with atypical molecular and functional identity. Compared to ‘classical’ Pomc neurons, Ghost neurons exhibit negligible Pomc expression and are ‘invisible’ to available neuroanatomical approaches and promoter-based reporter mice for studying Pomc biology. Ghost neuron numbers augment in diet-induced obese mice, independent of neurogenesis or cell death, but weight loss can reverse this shift. Our work challenges the notion of fixed, developmentally programmed neuronal identities in the mature hypothalamus and highlight the ability of specialised neurons to reversibly adapt their functional identity to adult-onset obesogenic stimuli.
Synergism between two BLA-to-BNST pathways for appropriate expression of anxiety-like behaviors in male mice
Authors: Han Ren-Wen , Zhang Zi-Yi , Jiao Chen , Hu Ze-Yu , Pan Bing-Xing 
Published: April 2024

AbstractUnderstanding how distinct functional circuits are coordinated to fine-tune mood and behavior is of fundamental importance. Here, we observe that within the dense projections from basolateral amygdala (BLA) to bed nucleus of stria terminalis (BNST), there are two functionally opposing pathways orchestrated to enable contextually appropriate expression of anxiety-like behaviors in male mice. Specifically, the anterior BLA neurons predominantly innervate the anterodorsal BNST (adBNST), while their posterior counterparts send massive fibers to oval BNST (ovBNST) with moderate to adBNST. Optogenetic activation of the anterior and posterior BLA inputs oppositely regulated the activity of adBNST neurons and anxiety-like behaviors, via disengaging and engaging the inhibitory ovBNST-to-adBNST microcircuit, respectively. Importantly, the two pathways exhibited synchronized but opposite responses to both anxiolytic and anxiogenic stimuli, partially due to their mutual inhibition within BLA and the different inputs they receive. These findings reveal synergistic interactions between two BLA-to-BNST pathways for appropriate anxiety expression with ongoing environmental demands.