bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contactin-associated protein-like 2 (CNTNAP2) mutations impair the essential α-secretase cleavages, leading to autism-like phenotypes
Authors: Zhang Qing , Xing Mengen , Bao Zhengkai , Xu Lu , Bai Yang , Chen Wanqi , Pan Wenhao , Cai Fang , Wang Qunxian , Guo Shipeng , Zhang Jing , Wang Zhe , Wu Yili , Zhang Yun , Li Jia-Da , Song Weihong 
Published: March 2024

AbstractMutations in the Contactin-associated protein-like 2 (CNTNAP2) gene are associated with autism spectrum disorder (ASD), and ectodomain shedding of the CNTNAP2 protein plays a role in its function. However, key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown, and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain elusive. In this report we showed that CNTNAP2 undergoes sequential cleavages by furin, ADAM10/17-dependent α-secretase and presenilin-dependent γ-secretase. We identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96, and the main α-cleavage product C79 by ADAM10 is required for the subsequent γ-secretase cleavage to generate CNTNAP2 intracellular domain (CICD). ASD-associated CNTNAP2 mutations impair the α-cleavage to generate C79, and the inhibition leads to ASD-like repetitive and social behavior abnormalities in the Cntnap2-I1254T knock-in mice. Finally, exogenous expression of C79 improves autism-like phenotypes in the Cntnap2-I1254T knock-in and Cntnap2−/− knockout mice. This data demonstrates that the α-secretase is essential for CNTNAP2 processing and its function. Our study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis, and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.
TRIB3 promotes malignancy of head and neck squamous cell carcinoma via inhibiting ferroptosis
Authors: Chen Li , Lin Wanzun , Zhang Haojiong , Geng Shikai , Le Ziyu , Wan Fangzhu , Huang Qingting , Chen Huaiyuan , Liu Xingyu , Lu Jiade J. , Kong Lin 
Published: March 2024

AbstractTribbles pseudokinase 3 (TRIB3) has been identified recently as a novel oncogene in several cancers. Still, further extensive research is imperative to elucidate its function and the molecular mechanisms underlying its involvement in the progression of head and neck squamous cell carcinoma (HNSCC). In our study, we found that TRIB3 silencing significantly promoted cell death by inducing ferroptosis. The interaction of TRIB3 with Transcription Factor 4 (TCF4) and β-catenin created a heterotrimeric complex, which directly interacts with the ALOXE3 promoter, detrimentally impacting its activation. The consequential partial neutralization of ferroptosis induced by TRIB3 deficiency is observed through the implementation of ALOXE3 knockdown. Furthermore, the study demonstrated that the molecular inhibitor hesperidin, targeting TRIB3, not only reduced cell malignancy but also induced ferroptosis, thereby suppressing tumor growth. Overall, our findings unequivocally validate the proposition that TRIB3 deficiency precipitates the iron death mechanism, thereby indicating that the strategic targeting of TRIB3 could emerge as an innovative therapeutic strategy for HNSCC.
Depletion of the N6-Methyladenosine (m6A) reader protein IGF2BP3 induces ferroptosis in glioma by modulating the expression of GPX4
Authors: Deng Limei , Di Yunbo , Chen Caiyun , Xia Juan , Lei Bingxi , Li Ning , Zhang Qingyu 
Published: March 2024

AbstractEmerging evidence highlights the multifaceted contributions of m6A modifications to glioma. IGF2BP3, a m6A modification reader protein, plays a crucial role in post-transcriptional gene regulation. Though several studies have identified IGF2BP3 as a poor prognostic marker in glioma, the underlying mechanism remains unclear. In this study, we demonstrated that IGF2BP3 knockdown is detrimental to cell growth and survival in glioma cells. Notably, we discovered that IGF2BP3 regulated ferroptosis by modulating the protein expression level of GPX4 through direct binding to a specific motif on GPX4 mRNA. Strikingly, the m6A modification at this motif was found to be critical for GPX4 mRNA stability and translation. Furthermore, IGF2BP3 knockdown glioma cells were incapable of forming tumors in a mouse xenograft model and were more susceptible to phagocytosis by microglia. Our findings shed light on an unrecognized regulatory function of IGF2BP3 in ferroptosis. The identification of a critical m6A site within the GPX4 transcript elucidates the significance of post-transcriptional control in ferroptosis.
Mechanisms and significance of entosis for tumour growth and progression
Authors: Gaptulbarova Ksenia Аndreevna , Tsydenova Irina Alexandrovna , Dolgasheva Daria Sergeevna , Kravtsova Ekaterina Andreevna , Ibragimova Marina Konstantinovna , Vtorushin Sergey Vladimirovich , Litviakov Nikolai Vasilievich 
Published: March 2024

AbstractTo date, numerous mechanisms have been identified in which one cell engulfs another, resulting in the creation of ‘cell-in-cell’ (CIC) structures, which subsequently cause cell death. One of the mechanisms of formation of these structures is entosis, which is presumably associated with possible carcinogenesis and tumour progression. The peculiarity of the process is that entotic cells themselves actively invade the host cell, and afterwards have several possible variants of fate. Entotic formations are structures where one cell is engulfed by another cell, creating a cell-in-cell structure. The nucleus of the outer cell has a crescent shape, while the inner cell is surrounded by a large entotic vacuole. These characteristics differentiate entosis from cell cannibalism. It’s worth noting that entotic formations are not necessarily harmful and may even be beneficial in some cases. In this article we will consider the mechanism of entosis and variants of entotic cell death, and also put forward hypothesis about possible variants of participation of this process on the formation and progression of cancer. This article also presents our proposed classification of functional forms of entosis.
Biodegradable triboelectric nanogenerator as a implantable power source for embedded medicine devices
Authors: Jian Gang , Zhu Shangtao , Yuan Xiao , Fu Shengqiao , Yang Ning , Yan Chao , Wang Xu , Wong Ching-Ping 
Published: March 2024

Abstract
Implantable medical devices have played an important role in human medicine in recent decades. However, traditional implanted devices require battery replacement and a second surgery for device removal, which can cause pain to the patient. This work presents a biodegradable triboelectric nanogenerator (BI-TENG) made from both natural and synthetic biodegradable materials that is utilized to collect mechanical energy in vivo and transduce it into electricity. Reed film and polylactic acid were chosen among different biodegradable materials as the triboelectric layers due to having the best generator output performance by providing voltages that reached 368 V. The biocompatibility of the friction layer and the device was verified via a blood test. After implantation in mice, the BI-TENG exhibited an open-circuit voltage of 0.176 V and a short-circuit current of 192 nA as generated from body movement. The BI-TENG was connected to an interdigital electrode to generate an electric field, which stimulated the accelerated release of doxorubicin (DOX) from red blood cells in targeted drug delivery systems. After stopping the electric field, the release of DOX normalized, facilitating the precise killing of cancer cells. Our work demonstrates the broad potential of BI-TENGs in the field of cancer treatment.
Gestational vitamin D and offspring fracture risk: do associations persist into mid adolescence?
Authors: Percival Mia A. , Anderson Kara B. , Pasco Julie A. , Hosking Sarah M. , Williams Lana J. , Holloway-Kew Kara L. , Wark John D. , Hyde Natalie K. 
Published: March 2024

Abstract
Background
Previous studies report that maternal vitamin D exposure during pregnancy is associated with offspring later-life bone health. A study in the Vitamin D in Pregnancy (VIP) cohort reported sexually dimorphic effects of maternal 25-hydroxyvitamin-D (25(OH)D) and offspring fracture profiles at 10 years of age. We, therefore, aimed to determine associations between maternal 25(OH)D status and offspring fracture risk at 16 years of age in this cohort.

Methods
In total, 475 mother-child pairs were recruited to the VIP study in southeastern Australia. Maternal serum samples were obtained at recruitment (<16 weeks’ gestation) and/or 28–32 weeks’ gestation and analysed for 25(OH)D. Radiologically-confirmed incident fractures in children were ascertained from date of birth (2002–2004) until July 16, 2019. Cox proportional hazard models were used to determine associations between maternal 25(OH)D and childhood fracture risk, and final models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of 25(OH)D sample.

Results
Data were available for 400 children (mean age 16.1 years). There were 122 (30.5%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10 nmol/L) in early gestation was associated with a decreased fracture risk in boys (HR 0.87; 95% CI: 0.77, 0.99); the pattern was reversed in girls (HR 1.10; 95% CI 1.00, 1.22). At late gestation, higher maternal 25(OH)D was associated with an increased fracture risk in girls (HR 1.14; 95% CI: 1.04, 1.24).

Conclusions
While our findings must be interpreted within the constraints of our limitations, we report that the contradictory risk profiles observed at early childhood in this cohort remain in adolescence.
Competing itinerant and local spin interactions in kagome metal FeGe
Authors: Chen Lebing , Teng Xiaokun , Tan Hengxin , Winn Barry L. , Granroth Garrett E. , Ye Feng , Yu D. H. , Mole R. A. , Gao Bin , Yan Binghai , Yi Ming , Dai Pengcheng 
Published: March 2024

AbstractThe combination of a geometrically frustrated lattice, and similar energy scales between degrees of freedom endows two-dimensional Kagome metals with a rich array of quantum phases and renders them ideal for studying strong electron correlations and band topology. The Kagome metal, FeGe is a noted example of this, exhibiting A-type collinear antiferromagnetic (AFM) order at TN ≈ 400 K, then establishes a charge density wave (CDW) phase coupled with AFM ordered moment below TCDW ≈ 110 K, and finally forms a c-axis double cone AFM structure around TCanting ≈ 60 K. Here we use neutron scattering to demonstrate the presence of gapless incommensurate spin excitations associated with the double cone AFM structure of FeGe at temperatures well above TCanting and TCDW that merge into gapped commensurate spin waves from the A-type AFM order. Commensurate spin waves follow the Bose factor and fit the Heisenberg Hamiltonian, while the incommensurate spin excitations, emerging below TN where AFM order is commensurate, start to deviate from the Bose factor around TCDW, and peaks at TCanting. This is consistent with a critical scattering of a second order magnetic phase transition with decreasing temperature. By comparing these results with density functional theory calculations, we conclude that the incommensurate magnetic structure arises from the nested Fermi surfaces of itinerant electrons and the formation of a spin density wave order.
CD8+ T cell priming that is required for curative intratumorally anchored anti-4-1BB immunotherapy is constrained by Tregs
Authors: Palmeri Joseph R. , Lax Brianna M. , Peters Joshua M. , Duhamel Lauren , Stinson Jordan A. , Santollani Luciano , Lutz Emi A. , Pinney William , Bryson Bryan D. , Dane Wittrup K. 
Published: March 2024

AbstractAlthough co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical success has been limited by on-target, off-tumor activity. Here, we report the development of a tumor-anchored ɑ4-1BB agonist (ɑ4-1BB-LAIR), which consists of a ɑ4-1BB antibody fused to the collagen-binding protein LAIR. While combination treatment with an antitumor antibody (TA99) shows only modest efficacy, simultaneous depletion of CD4+ T cells boosts cure rates to over 90% of mice. Mechanistically, this synergy depends on ɑCD4 eliminating tumor draining lymph node regulatory T cells, resulting in priming and activation of CD8+ T cells which then infiltrate the tumor microenvironment. The cytotoxic program of these newly primed CD8+ T cells is then supported by the combined effect of TA99 and ɑ4-1BB-LAIR. The combination of TA99 and ɑ4-1BB-LAIR with a clinically approved ɑCTLA-4 antibody known for enhancing T cell priming results in equivalent cure rates, which validates the mechanistic principle, while the addition of ɑCTLA-4 also generates robust immunological memory against secondary tumor rechallenge. Thus, our study establishes the proof of principle for a clinically translatable cancer immunotherapy.
Voltage-based magnetization switching and reading in magnetoelectric spin-orbit nanodevices
Authors: Vaz Diogo C. , Lin Chia-Ching , Plombon John J. , Choi Won Young , Groen Inge , Arango Isabel C. , Chuvilin Andrey , Hueso Luis E. , Nikonov Dmitri E. , Li Hai , Debashis Punyashloka , Clendenning Scott B. , Gosavi Tanay A. , Huang Yen-Lin , Prasad Bhagwati , Ramesh Ramamoorthy , Vecchiola Aymeric , Bibes Manuel , Bouzehouane Karim , Fusil Stephane , Garcia Vincent , Young Ian A. , Casanova Fèlix 
Published: March 2024

AbstractAs CMOS technologies face challenges in dimensional and voltage scaling, the demand for novel logic devices has never been greater, with spin-based devices offering scaling potential, at the cost of significantly high switching energies. Alternatively, magnetoelectric materials are predicted to enable low-power magnetization control, a solution with limited device-level results. Here, we demonstrate voltage-based magnetization switching and reading in nanodevices at room temperature, enabled by exchange coupling between multiferroic BiFeO3 and ferromagnetic CoFe, for writing, and spin-to-charge current conversion between CoFe and Pt, for reading. We show that, upon the electrical switching of the BiFeO3, the magnetization of the CoFe can be reversed, giving rise to different voltage outputs. Through additional microscopy techniques, magnetization reversal is linked with the polarization state and antiferromagnetic cycloid propagation direction in the BiFeO3. This study constitutes the building block for magnetoelectric spin-orbit logic, opening a new avenue for low-power beyond-CMOS technologies.
Superconductivity in a van der Waals layered quasicrystal
Authors: Tokumoto Yuki , Hamano Kotaro , Nakagawa Sunao , Kamimura Yasushi , Suzuki Shintaro , Tamura Ryuji , Edagawa Keiichi 
Published: March 2024

AbstractVan der Waals layered transition-metal chalcogenides are drawing significant attention owing to their intriguing physical properties. This group of materials consists of abundant members with various elements, having a variety of different structures. However, they are all crystalline materials, and the physical properties of van der Waals layered quasicrystals have never been studied to date. Here, we report on the discovery of superconductivity in a van der Waals layered quasicrystal of Ta1.6Te. The electrical resistivity, magnetic susceptibility, and specific heat of the quasicrystal unambiguously validate the occurrence of bulk superconductivity at a transition temperature of ~1 K. This discovery can promote new research on assessing the physical properties of novel van der Waals layered quasicrystals as well as two-dimensional quasicrystals; moreover, it paves the way toward new frontiers of superconductivity in thermodynamically stable quasicrystals.
Protein NirP1 regulates nitrite reductase and nitrite excretion in cyanobacteria
Authors: Kraus Alexander , Spät Philipp , Timm Stefan , Wilson Amy , Schumann Rhena , Hagemann Martin , Maček Boris , Hess Wolfgang R. 
Published: March 2024

AbstractWhen the supply of inorganic carbon is limiting, photosynthetic cyanobacteria excrete nitrite, a toxic intermediate in the ammonia assimilation pathway from nitrate. It has been hypothesized that the excreted nitrite represents excess nitrogen that cannot be further assimilated due to the missing carbon, but the underlying molecular mechanisms are unclear. Here, we identified a protein that interacts with nitrite reductase, regulates nitrogen metabolism and promotes nitrite excretion. The protein, which we named NirP1, is encoded by an unannotated gene that is upregulated under low carbon conditions and controlled by transcription factor NtcA, a central regulator of nitrogen homeostasis. Ectopic overexpression of nirP1 in Synechocystis sp. PCC 6803 resulted in a chlorotic phenotype, delayed growth, severe changes in amino acid pools, and nitrite excretion. Coimmunoprecipitation experiments indicated that NirP1 interacts with nitrite reductase, a central enzyme in the assimilation of ammonia from nitrate/nitrite. Our results reveal that NirP1 is widely conserved in cyanobacteria and plays a crucial role in the coordination of C/N primary metabolism by targeting nitrite reductase.
Dynamic control of DNA condensation
Authors: Agarwal Siddharth , Osmanovic Dino , Dizani Mahdi , Klocke Melissa A. , Franco Elisa 
Published: March 2024

AbstractArtificial biomolecular condensates are emerging as a versatile approach to organize molecular targets and reactions without the need for lipid membranes. Here we ask whether the temporal response of artificial condensates can be controlled via designed chemical reactions. We address this general question by considering a model problem in which a phase separating component participates in reactions that dynamically activate or deactivate its ability to self-attract. Through a theoretical model we illustrate the transient and equilibrium effects of reactions, linking condensate response and reaction parameters. We experimentally realize our model problem using star-shaped DNA motifs known as nanostars to generate condensates, and we take advantage of strand invasion and displacement reactions to kinetically control the capacity of nanostars to interact. We demonstrate reversible dissolution and growth of DNA condensates in the presence of specific DNA inputs, and we characterize the role of toehold domains, nanostar size, and nanostar valency. Our results will support the development of artificial biomolecular condensates that can adapt to environmental changes with prescribed temporal dynamics.
The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration
Authors: Sachs Wiebke , Blume Lukas , Loreth Desiree , Schebsdat Lisa , Hatje Favian , Koehler Sybille , Wedekind Uta , Sachs Marlies , Zieliniski Stephanie , Brand Johannes , Conze Christian , Florea Bogdan I. , Heppner Frank , Krüger Elke , Rinschen Markus M. , Kretz Oliver , Thünauer Roland , Meyer-Schwesinger Catherine 
Published: March 2024

AbstractKidney filtration is ensured by the interaction of podocytes, endothelial and mesangial cells. Immunoglobulin accumulation at the filtration barrier is pathognomonic for glomerular injury. The mechanisms that regulate filter permeability are unknown. Here, we identify a pivotal role for the proteasome in a specific cell type. Combining genetic and inhibitor-based human, pig, mouse, and Drosophila models we demonstrate that the proteasome maintains filtration barrier integrity, with podocytes requiring the constitutive and glomerular endothelial cells the immunoproteasomal activity. Endothelial immunoproteasome deficiency as well as proteasome inhibition disrupt the filtration barrier in mice, resulting in pathologic immunoglobulin deposition. Mechanistically, we observe reduced endocytic activity, which leads to altered membrane recycling and endocytic receptor turnover. This work expands the concept of the (immuno)proteasome as a control protease orchestrating protein degradation and antigen presentation and endocytosis, providing new therapeutic targets to treat disease-associated glomerular protein accumulations.
A comprehensive transformer-based approach for high-accuracy gas adsorption predictions in metal-organic frameworks
Authors: Wang Jingqi , Liu Jiapeng , Wang Hongshuai , Zhou Musen , Ke Guolin , Zhang Linfeng , Wu Jianzhong , Gao Zhifeng , Lu Diannan 
Published: March 2024

AbstractGas separation is crucial for industrial production and environmental protection, with metal-organic frameworks (MOFs) offering a promising solution due to their tunable structural properties and chemical compositions. Traditional simulation approaches, such as molecular dynamics, are complex and computationally demanding. Although feature engineering-based machine learning methods perform better, they are susceptible to overfitting because of limited labeled data. Furthermore, these methods are typically designed for single tasks, such as predicting gas adsorption capacity under specific conditions, which restricts the utilization of comprehensive datasets including all adsorption capacities. To address these challenges, we propose Uni-MOF, an innovative framework for large-scale, three-dimensional MOF representation learning, designed for multi-purpose gas prediction. Specifically, Uni-MOF serves as a versatile gas adsorption estimator for MOF materials, employing pure three-dimensional representations learned from over 631,000 collected MOF and COF structures. Our experimental results show that Uni-MOF can automatically extract structural representations and predict adsorption capacities under various operating conditions using a single model. For simulated data, Uni-MOF exhibits remarkably high predictive accuracy across all datasets. Additionally, the values predicted by Uni-MOF correspond with the outcomes of adsorption experiments. Furthermore, Uni-MOF demonstrates considerable potential for broad applicability in predicting a wide array of other properties.
Warming underpins community turnover in temperate freshwater and terrestrial communities
Authors: Khaliq Imran , Rixen Christian , Zellweger Florian , Graham Catherine H. , Gossner Martin M. , McFadden Ian R. , Antão Laura , Brodersen Jakob , Ghosh Shyamolina , Pomati Francesco , Seehausen Ole , Roth Tobias , Sattler Thomas , Supp Sarah R. , Riaz Maria , Zimmermann Niklaus E. , Matthews Blake , Narwani Anita 
Published: March 2024

AbstractRising temperatures are leading to increased prevalence of warm-affinity species in ecosystems, known as thermophilisation. However, factors influencing variation in thermophilisation rates among taxa and ecosystems, particularly freshwater communities with high diversity and high population decline, remain unclear. We analysed compositional change over time in 7123 freshwater and 6201 terrestrial, mostly temperate communities from multiple taxonomic groups. Overall, temperature change was positively linked to thermophilisation in both realms. Extirpated species had lower thermal affinities in terrestrial communities but higher affinities in freshwater communities compared to those persisting over time. Temperature change’s impact on thermophilisation varied with community body size, thermal niche breadth, species richness and baseline temperature; these interactive effects were idiosyncratic in the direction and magnitude of their impacts on thermophilisation, both across realms and taxonomic groups. While our findings emphasise the challenges in predicting the consequences of temperature change across communities, conservation strategies should consider these variable responses when attempting to mitigate climate-induced biodiversity loss.