bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-184 represses β-catenin and behaves as a skin tumor suppressor
Authors: Turovsky Lubov , Kheshaiboun Ghazal , Yassen Gharam , Nagosa Sara , Boyango Ilanit , Amitai-Lange Aya , Bhattacharya Swarnabh , Ilan Neta , Vlodavsky Israel , Aberdam Daniel , Shalom-Feuerstein Ruby , Avitan-Hersh Emily 
Published: February 2024

AbstractmiR-184-knockout mice display perturbed epidermal stem cell differentiation. However, the potential role of miR-184 in skin pathology is unclear. Here, we report that miR-184 controls epidermal stem cell dynamics and that miR-184 ablation enhances skin carcinogenesis in mice. In agreement, repression of miR-184 in human squamous cell carcinoma (SCC) enhances neoplastic hallmarks of human SCC cells in vitro and tumor development in vivo. Characterization of miR-184-regulatory network, suggests that miR-184 inhibits pro-oncogenic pathways, cell proliferation, and epithelial to mesenchymal transformation. Of note, depletion of miR-184 enhances the levels of β-catenin under homeostasis and following experimental skin carcinogenesis. Finally, the repression of β-catenin by miR-184, inhibits the neoplastic phenotype of SCC cells. Taken together, miR-184 behaves as an epidermal tumor suppressor, and may provide a potentially useful target for skin SCC therapy.
SPOP point mutations regulate substrate preference and affect its function
Authors: Deng Yanran , Ding Wenhao , Ma Kaize , Zhan Meixiao , Sun Li , Zhou Zizhang , Lu Ligong 
Published: February 2024

AbstractThe adaptor SPOP recruits substrates to CUL3 E3 ligase for ubiquitination and degradation. Structurally, SPOP harbors a MATH domain for substrate recognition, and a BTB domain responsible for binding CUL3. Reported point mutations always occur in SPOP’s MATH domain and are through to disrupt affinities of SPOP to substrates, thereby leading to tumorigenesis. In this study, we identify the tumor suppressor IRF2BP2 as a novel substrate of SPOP. SPOP enables to attenuate IRF2BP2-inhibited cell proliferation and metastasis in HCC cells. However, overexpression of wild-type SPOP alone suppresses HCC cell proliferation and metastasis. In addition, a HCC-derived mutant, SPOP-M35L, shows an increased affinity to IRF2BP2 in comparison with wild-type SPOP. SPOP-M35L promotes HCC cell proliferation and metastasis, suggesting that M35L mutation possibly reprograms SPOP from a tumor suppressor to an oncoprotein. Taken together, this study uncovers mutations in SPOP’s MATH lead to distinct functional consequences in context-dependent manners, rather than simply disrupting its interactions with substrates, raising a noteworthy concern that we should be prudent to select SPOP as therapeutic target for cancers.
Amorphous alloys surpass E/10 strength limit at extreme strain rates
Authors: Zhu Wenqing , Li Zhi , Shu Hua , Gao Huajian , Wei Xiaoding 
Published: February 2024

AbstractTheoretical predictions of the ideal strength of materials range from E/30 to E/10 (E is Young’s modulus). However, despite intense interest over the last decade, the value of the ideal strength achievable through experiments for metals remains a mystery. This study showcases the remarkable spall strength of Cu50Zr50 amorphous alloy that exceeds the E/10 limit at strain rates greater than 107 s−1 through laser-induced shock experiments. The material exhibits a spall strength of 11.5 GPa, approximately E/6 or 1/13 of its P-wave modulus, which sets a record for the elastic limit of metals. Electron microscopy and large-scale molecular dynamics simulations reveal that the primary failure mechanism at extreme strain rates is void nucleation and growth, rather than shear-banding. The rate dependence of material strength is explained by a void kinetic model controlled by surface energy. These findings help advance our understanding on the mechanical behavior of amorphous alloys under extreme strain rates.
In situ combinatorial synthesis of degradable branched lipidoids for systemic delivery of mRNA therapeutics and gene editors
Authors: Han Xuexiang , Xu Junchao , Xu Ying , Alameh Mohamad-Gabriel , Xue Lulu , Gong Ningqiang , El-Mayta Rakan , Palanki Rohan , Warzecha Claude C. , Zhao Gan , Vaughan Andrew E. , Wilson James M. , Weissman Drew , Mitchell Michael J. 
Published: February 2024

AbstractThe ionizable lipidoid is a key component of lipid nanoparticles (LNPs). Degradable lipidoids containing extended alkyl branches have received tremendous attention, yet their optimization and investigation are underappreciated. Here, we devise an in situ construction method for the combinatorial synthesis of degradable branched (DB) lipidoids. We find that appending branch tails to inefficacious lipidoids via degradable linkers boosts mRNA delivery efficiency up to three orders of magnitude. Combinatorial screening and systematic investigation of two libraries of DB-lipidoids reveal important structural criteria that govern their in vivo potency. The lead DB-LNP demonstrates robust delivery of mRNA therapeutics and gene editors into the liver. In a diet-induced obese mouse model, we show that repeated administration of DB-LNP encapsulating mRNA encoding human fibroblast growth factor 21 alleviates obesity and fatty liver. Together, we offer a construction strategy for high-throughput and cost-efficient synthesis of DB-lipidoids. This study provides insights into branched lipidoids for efficient mRNA delivery.
Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells
Authors: Costa Bibiana , Becker Jennifer , Krammer Tobias , Mulenge Felix , Durán Verónica , Pavlou Andreas , Gern Olivia Luise , Chu Xiaojing , Li Yang , Čičin-Šain Luka , Eiz-Vesper Britta , Messerle Martin , Dölken Lars , Saliba Antoine-Emmanuel , Erhard Florian , Kalinke Ulrich 
Published: February 2024

AbstractHuman cytomegalovirus (HCMV) is a widespread pathogen that in immunocompromised hosts can cause life-threatening disease. Studying HCMV-exposed monocyte-derived dendritic cells by single-cell RNA sequencing, we observe that most cells are entered by the virus, whereas less than 30% of them initiate viral gene expression. Increased viral gene expression is associated with activation of the stimulator of interferon genes (STING) that usually induces anti-viral interferon responses, and with the induction of several pro- (RHOB, HSP1A1, DNAJB1) and anti-viral (RNF213, TNFSF10, IFI16) genes. Upon progression of infection, interferon-beta but not interferon-lambda transcription is inhibited. Similarly, interferon-stimulated gene expression is initially induced and then shut off, thus further promoting productive infection. Monocyte-derived dendritic cells are composed of 3 subsets, with one being especially susceptible to HCMV. In conclusion, HCMV permissiveness of monocyte-derived dendritic cells depends on complex interactions between virus sensing, regulation of the interferon response, and viral gene expression.
Dual-site segmentally synergistic catalysis mechanism: boosting CoFeSx nanocluster for sustainable water oxidation
Authors: Xu Siran , Feng Sihua , Yu Yue , Xue Dongping , Liu Mengli , Wang Chao , Zhao Kaiyue , Xu Bingjun , Zhang Jia-Nan 
Published: February 2024

AbstractEfficient oxygen evolution reaction electrocatalysts are essential for sustainable clean energy conversion. However, catalytic materials followed the conventional adsorbate evolution mechanism (AEM) with the inherent scaling relationship between key oxygen intermediates *OOH and *OH, or the lattice-oxygen-mediated mechanism (LOM) with the possible lattice oxygen migration and structural reconstruction, which are not favorable to the balance between high activity and stability. Herein, we propose an unconventional Co-Fe dual-site segmentally synergistic mechanism (DSSM) for single-domain ferromagnetic catalyst CoFeSx nanoclusters on carbon nanotubes (CNT) (CFS-ACs/CNT), which can effectively break the scaling relationship without sacrificing stability. Co3+ (L.S, t2g6eg0) supplies the strongest OH* adsorption energy, while Fe3+ (M.S, t2g4eg1) exposes strong O* adsorption. These dual-sites synergistically produce of Co-O-O-Fe intermediates, thereby accelerating the release of triplet-state oxygen ( ↑ O = O ↑ ). As predicted, the prepared CFS-ACs/CNT catalyst exhibits less overpotential than that of commercial IrO2, as well as approximately 633 h of stability without significant potential loss.
Removal of detritivore sea cucumbers from reefs increases coral disease
Authors: Clements Cody S. , Pratte Zoe A. , Stewart Frank J. , Hay Mark E. 
Published: February 2024

AbstractCoral reefs are in global decline with coral diseases playing a significant role. This is especially true for Acroporid corals that represent ~25% of all Pacific coral species and generate much of the topographic complexity supporting reef biodiversity. Coral diseases are commonly sediment-associated and could be exacerbated by overharvest of sea cucumber detritivores that clean reef sediments and may suppress microbial pathogens as they feed. Here we show, via field manipulations in both French Polynesia and Palmyra Atoll, that historically overharvested sea cucumbers strongly suppress disease among corals in contact with benthic sediments. Sea cucumber removal increased tissue mortality of Acropora pulchra by ~370% and colony mortality by ~1500%. Additionally, farmerfish that kill Acropora pulchra bases to culture their algal gardens further suppress disease by separating corals from contact with the disease-causing sediment—functioning as mutualists rather than parasites despite killing coral bases. Historic overharvesting of sea cucumbers increases coral disease and threatens the persistence of tropical reefs. Enhancing sea cucumbers may enhance reef resilience by suppressing disease.
Engineering surface dipoles on mixed conducting oxides with ultra-thin oxide decoration layers
Authors: Siebenhofer Matthäus , Nenning Andreas , Rameshan Christoph , Blaha Peter , Fleig Jürgen , Kubicek Markus 
Published: February 2024

AbstractImproving materials for energy conversion and storage devices is deeply connected with an optimization of their surfaces and surface modification is a promising strategy on the way to enhance modern energy technologies. This study shows that surface modification with ultra-thin oxide layers allows for a systematic tailoring of the surface dipole and the work function of mixed ionic and electronic conducting oxides, and it introduces the ionic potential of surface cations as a readily accessible descriptor for these effects. The combination of X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) illustrates that basic oxides with a lower ionic potential than the host material induce a positive surface charge and reduce the work function of the host material and vice versa. As a proof of concept that this strategy is widely applicable to tailor surface properties, we examined the effect of ultra-thin decoration layers on the oxygen exchange kinetics of pristine mixed conducting oxide thin films in very clean conditions by means of in-situ impedance spectroscopy during pulsed laser deposition (i-PLD). The study shows that basic decorations with a reduced surface work function lead to a substantial acceleration of the oxygen exchange on the surfaces of diverse materials.
Statistical method scDEED for detecting dubious 2D single-cell embeddings and optimizing t-SNE and UMAP hyperparameters
Authors: Xia Lucy , Lee Christy , Li Jingyi Jessica 
Published: February 2024

AbstractTwo-dimensional (2D) embedding methods are crucial for single-cell data visualization. Popular methods such as t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP) are commonly used for visualizing cell clusters; however, it is well known that t-SNE and UMAP’s 2D embeddings might not reliably inform the similarities among cell clusters. Motivated by this challenge, we present a statistical method, scDEED, for detecting dubious cell embeddings output by a 2D-embedding method. By calculating a reliability score for every cell embedding based on the similarity between the cell’s 2D-embedding neighbors and pre-embedding neighbors, scDEED identifies the cell embeddings with low reliability scores as dubious and those with high reliability scores as trustworthy. Moreover, by minimizing the number of dubious cell embeddings, scDEED provides intuitive guidance for optimizing the hyperparameters of an embedding method. We show the effectiveness of scDEED on multiple datasets for detecting dubious cell embeddings and optimizing the hyperparameters of t-SNE and UMAP.
Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice
Authors: Durand Aurélie , Bonilla Nelly , Level Théo , Ginestet Zoé , Lombès Amélie , Guichard Vincent , Germain Mathieu , Jacques Sébastien , Letourneur Franck , Do Cruzeiro Marcio , Marchiol Carmen , Renault Gilles , Le Gall Morgane , Charvet Céline , Le Bon Agnès , Martin Bruno , Auffray Cédric , Lucas Bruno 
Published: February 2024

AbstractFoxo family transcription factors are critically involved in multiple processes, such as metabolism, quiescence, cell survival and cell differentiation. Although continuous, high activity of Foxo transcription factors extends the life span of some species, the involvement of Foxo proteins in mammalian aging remains to be determined. Here, we show that Foxo1 is down-regulated with age in mouse T cells. This down-regulation of Foxo1 in T cells may contribute to the disruption of naive T-cell homeostasis with age, leading to an increase in the number of memory T cells. Foxo1 down-regulation is also associated with the up-regulation of co-inhibitory receptors by memory T cells and exhaustion in aged mice. Using adoptive transfer experiments, we show that the age-dependent down-regulation of Foxo1 in T cells is mediated by T-cell-extrinsic cues, including type 1 interferons. Taken together, our data suggest that type 1 interferon-induced Foxo1 down-regulation is likely to contribute significantly to T-cell dysfunction in aged mice.
A distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study
Authors: Chen Hui , Wang Zeyang , Gong Lihai , Wang Qixuan , Chen Wenyan , Wang Jia , Ma Xuelian , Ding Ruofan , Li Xing , Zou Xudong , Plass Mireya , Lian Cheng , Ni Ting , Wei Gong-Hong , Li Wei , Deng Lin , Li Lei 
Published: February 2024

AbstractAlternative polyadenylation plays an important role in cancer initiation and progression; however, current transcriptome-wide association studies mostly ignore alternative polyadenylation when identifying putative cancer susceptibility genes. Here, we perform a pan-cancer 3′ untranslated region alternative polyadenylation transcriptome-wide association analysis by integrating 55 well-powered (n > 50,000) genome-wide association studies datasets across 22 major cancer types with alternative polyadenylation quantification from 23,955 RNA sequencing samples across 7,574 individuals. We find that genetic variants associated with alternative polyadenylation are co-localized with 28.57% of cancer loci and contribute a significant portion of cancer heritability. We further identify 642 significant cancer susceptibility genes predicted to modulate cancer risk via alternative polyadenylation, 62.46% of which have been overlooked by traditional expression- and splicing- studies. As proof of principle validation, we show that alternative alleles facilitate 3′ untranslated region lengthening of CRLS1 gene leading to increased protein abundance and promoted proliferation of breast cancer cells. Together, our study highlights the significant role of alternative polyadenylation in discovering new cancer susceptibility genes and provides a strong foundational framework for enhancing our understanding of the etiology underlying human cancers.
Pooled effector library screening in protoplasts rapidly identifies novel Avr genes
Authors: Arndell Taj , Chen Jian , Sperschneider Jana , Upadhyaya Narayana M. , Blundell Cheryl , Niesner Nathalie , Outram Megan A. , Wang Aihua , Swain Steve , Luo Ming , Ayliffe Michael A. , Figueroa Melania , Vanhercke Thomas , Dodds Peter N. 
Published: February 2024

AbstractCrop breeding for durable disease resistance is challenging due to the rapid evolution of pathogen virulence. While progress in resistance (R) gene cloning and stacking has accelerated in recent years1–3, the identification of corresponding avirulence (Avr) genes in many pathogens is hampered by the lack of high-throughput screening options. To address this technology gap, we developed a platform for pooled library screening in plant protoplasts to allow rapid identification of interacting R–Avr pairs. We validated this platform by isolating known and novel Avr genes from wheat stem rust (Puccinia graminis f. sp. tritici) after screening a designed library of putative effectors against individual R genes. Rapid Avr gene identification provides molecular tools to understand and track pathogen virulence evolution via genotype surveillance, which in turn will lead to optimized R gene stacking and deployment strategies. This platform should be broadly applicable to many crop pathogens and could potentially be adapted for screening genes involved in other protoplast-selectable traits.
Robust training of machine learning interatomic potentials with dimensionality reduction and stratified sampling
Authors: Qi Ji , Ko Tsz Wai , Wood Brandon C. , Pham Tuan Anh , Ong Shyue Ping 
Published: February 2024

AbstractMachine learning interatomic potentials (MLIPs) enable accurate simulations of materials at scales beyond that accessible by ab initio methods and play an increasingly important role in the study and design of materials. However, MLIPs are only as accurate and robust as the data on which they are trained. Here, we present DImensionality-Reduced Encoded Clusters with sTratified (DIRECT) sampling as an approach to select a robust training set of structures from a large and complex configuration space. By applying DIRECT sampling on the Materials Project relaxation trajectories dataset with over one million structures and 89 elements, we develop an improved materials 3-body graph network (M3GNet) universal potential that extrapolates more reliably to unseen structures. We further show that molecular dynamics (MD) simulations with the M3GNet universal potential can be used instead of expensive ab initio MD to rapidly create a large configuration space for target systems. We combined this scheme with DIRECT sampling to develop a reliable moment tensor potential for titanium hydrides without the need for iterative augmentation of training structures. This work paves the way for robust high-throughput development of MLIPs across any compositional complexity.
Transitions in health insurance among continuously insured patients with schizophrenia
Authors: Ranchoff Brittany L. , Jeung Chanup , Zeber John E. , Simon Gregory E. , Ericson Keith M. , Qian Jing , Geissler Kimberley H. 
Published: February 2024

AbstractChanges in health insurance coverage may disrupt access to and continuity of care, even for those who remain insured. Continuity of care is especially important in schizophrenia, which requires ongoing medical and pharmaceutical treatment. However, little is known about continuity of insurance coverage among those with schizophrenia. The objective was to examine the probability of insurance transitions for individuals with schizophrenia who were continuously insured and whether this varied across insurance types. The Massachusetts All-Payer Claims Database identified individuals with schizophrenia aged 18–64 who were continuously insured during a two-year period between 2014 and 2018. A logistic regression estimated the association of having an insurance transition – defined as having a change in insurance type – with insurance type at the start of the period, adjusting for age, sex, ZIP code in the lowest quartile of median income, and ZIP code with concentrated poverty. Overall, 15.1% had at least one insurance transition across a 24-month period. Insurance transitions were most frequent among those with plans from the Marketplace. In regression adjusted results, individuals covered by the traditional Medicaid program were 20.2 percentage points [pp] (95% confidence interval [CI]: 24.6 pp, 15.9 pp) less likely to have an insurance transition than those who were insured by a Marketplace plan. Insurance transitions among individuals with schizophrenia were common, with more than one in six people having at least one transition in insurance type during a two-year period. Given that even continuously insured individuals with schizophrenia commonly experience insurance transitions, attention to insurance transitions as a barrier to care access and continuity is warranted.
Impact of sex on humoral immunity with live influenza B virus vaccines in mice
Authors: Cardenas-Garcia Stivalis , Cáceres C. Joaquín , Jain Aarti , Geiger Ginger , Mo Jong-Suk , Gay L. Claire , Seibert Brittany , Jasinskas Algimantas , Nakajima Rie , Rajao Daniela S. , Davies D. Huw , Perez Daniel R. 
Published: February 2024

AbstractInfluenza B virus (FLUBV) poses a significant infectious threat, with frequent vaccine mismatch limiting its effectiveness. Our previous work investigated the safety and efficacy of modified live attenuated FLUBV vaccines with rearranged genomes (FluB-RAM and FluB-RANS) or a temperature-sensitive PB1 segment with a C-terminal HA tag (FluB-att). In this study, we compared the immune responses of female and male DBA/2J mice vaccinated with these vaccines, including versions containing a chimeric HA segment with an N-terminal IgA-inducing peptide (IGIP). Importantly, both recombinant viruses with and without IGIP remained genetically stable during egg passage. We found that introducing IGIP strengthened vaccine attenuation, particularly for FluB-RAM/IGIP. Prime-boost vaccination completely protected mice against lethal challenge with a homologous FLUBV strain. Notably, recombinant viruses induced robust neutralizing antibody responses (hemagglutination inhibition titers ≥40) alongside antibodies against NA and NP. Interestingly, female mice displayed a consistent trend of enhanced humoral and cross-reactive IgG and IgA responses against HA, NA, and NP compared to male counterparts, regardless of the vaccine used. However, the presence of IGIP generally led to lower anti-HA responses but higher anti-NA and anti-NP responses, particularly of the IgA isotype. These trends were further reflected in mucosal and serological responses two weeks after challenge, with clear distinctions based on sex, vaccine backbone, and IGIP inclusion. These findings hold significant promise for advancing the development of universal influenza vaccines.