bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-canonical activation of PAR1 induces autophagy in mammalian breast cancer cells
Authors: Saha Saibal , Kumar Rishikesh , Sarangi Snehanjan , Tapader Rima , Ray Tanusree , Gope Animesh , Nag Niraj , Pal Ananda , Pal Amit 
Published: January 2025

AbstractThe question of whether autophagy is a boon or a bane for the body does not lend itself to a straightforward answer, as its consequences are intricately tied to the pathophysiological context that triggers its activation. The intricate nature of autophagy’s effects on the body, compounded by its multifaceted regulation through various upstream signaling pathways, warrants a deeper and more nuanced research. This study delves into the regulation of autophagy through the non-canonical activation of protease activated receptor 1 (hereafter, termed as PAR1) by Hemagglutinin protease (hereafter, referred as HAP). In contrast to the canonical activation of PAR1 by thrombin, which promotes cell proliferation via the upregulation of mTOR signaling, HAP-induced, non-canonical activation of PAR1 triggers autophagy by downregulating mTOR activation and modulating subsequent key signaling pathways in mammalian breast cancer cells. This non-canonical activation results in the generation of a new N-terminal sequence of PAR1. Moreover, synthetic peptide designed to replicate this newly generated N-terminal sequence effectively triggers autophagy in mammalian breast cancer cells, thereby establishing that induction of autophagy via non-canonical PAR1 activation is independent of the activating agent of PAR1 itself. The study also explores the implications of peptide-induced autophagy in the context of early-stage, low-grade breast cancer using a BALB/c mouse model, demonstrating substantial inhibition of tumor growth and a delay in carcinogenesis progression. Importantly, the absence of notable PAR1 expression in normal, healthy cells ensures that they remain unaffected by the peptide, positioning it as a promising candidate for targeted therapy in low-grade breast cancer.
Skeletal muscle mitochondria contain nuclear-encoded RNA species prior to and following adaptation to exercise training in rats
Authors: Silver Jessica L. , Lamon Séverine , Loke Stella , Mazzarino Gisella , Croft Larry , Ziemann Mark , Wadley Glenn. D. , Trewin Adam J. 
Published: January 2025

ABSTRACTSkeletal muscle mitochondria adaptation to exercise training is mediated by molecular factors that are not fully understood. Mitochondria import over 1000 proteins encoded by the nuclear genome, but the RNA population resident within the organelle is generally thought to be exclusively encoded by the mitochondrial genome. However, recentin vitroevidence suggests that specific nuclear-encoded miRNAs and other non-coding RNAs (ncRNAs) can reside within the mitochondrial matrix. Whether these are present in mitochondria of skeletal muscle tissue, and if this affected by endurance training - a potent metabolic stimulus for mitochondrial adaptation - remains unknown. Rats underwent four weeks of moderate intensity treadmill exercise training, then humanely killed and tissues collected for molecular profiling. Mitochondria from gastrocnemius skeletal muscle were isolated by immunoprecipitation, further purified, then the resident RNA was sequenced to assess the mitochondrial transcriptome. Exercise training elicited typical transcriptomic responses and functional adaptations in skeletal muscle, including increased mitochondrial respiratory capacity. We identified 24 nuclear-encoded, coding or non-coding RNAs in purified mitochondria, in addition to 50 nuclear-encoded miRNAs that met a specified abundance threshold. Although none were differentially expressed in the exercise vs control group at FDR<0.05, exploratory analyses suggested that the abundance of 3 miRNAs were altered (p<0.05) in mitochondria isolated from trained compared with sedentary skeletal muscle. We report the presence of a specific population of nuclear-encoded RNAs in the mitochondria isolated from rat skeletal muscle tissue, which could play a role in regulating exercise adaptations and mitochondrial biology.KEY POINTSMitochondria are a central metabolic and signalling hub, particularly in tissues with high energy demand such as skeletal muscle. Their ability to adapt to stimuli such as exercise training is directly related to improved metabolic health. Understanding the factors that regulate these adaptive processes is therefore essential.Mitochondria contain RNA encoded by their own genome (mtDNA); typically are not thought to contain nuclear-encoded RNA.Here, we report that mitochondria from rat skeletal muscle do indeed contain a select population of nuclear-encoded protein coding and non-coding RNAs, including 3 microRNAs whose expression tended to be altered by exercise training.These findings suggest that mitochondria-localised nuclear-encoded RNAs may play a role in mediating beneficial adaptive responses to exercise.
Initiation of primary T cell—B cell interactions and extrafollicular antibody responses in an organized microphysiological model of the human lymph node
Authors: Zatorski Jonathan M. , Raskovic Djuro , Arneja Abhinav , Kiridena Saweetha , Ozulumba Tochukwu , Hammel Jennifer H. , Anbaei Parastoo , Ortiz-Cárdenas Jennifer E. , Braciale Thomas J. , Munson Jennifer M. , Luckey Chance John , Pompano Rebecca R. 
Published: January 2025

ABSTRACTAntibody production is central to protection against new pathogens and cancers, as well as to certain forms of autoimmunity. Antibodies often originate in the lymph node (LN), specifically at the extrafollicular border of B cell follicles, where T and B lymphocytes physically interact to drive B cell maturation into antibody-secreting plasmablasts. In vitro models of this process are sorely needed to predict aspects of the human immune response. Microphysiological systems (MPSs) offer the opportunity to approximate the lymphoid environment, but so far have focused primarily on memory recall responses to antigens previously encountered by donor cells. To date, no 3D culture system has replicated the engagement between T cells and B cells (T—B interaction) that leads to antibody production when starting with naïve cells. Here, we developed a LN-MPS to model early T—B interactions at the extrafollicular border built from primary, naïve human lymphocytes encapsulated within a collagen-based 3D matrix. Within the MPS, naïve T cells exhibited CCL21-dependent chemotaxis and chemokinesis as predicted. Naïve T and B cells were successfully skewed on chip to an early T follicular helper (pre-Tfh) and activated state, respectively, and co-culture of the latter cells led to CD38+ plasmablast cells and T cell dependent production of IgM. These responses required differentiation of the T cells into pre-Tfhs, physical cell-cell contact, and were sensitive to the ratio at which pre-Tfh and activated B cells were seeded on-chip. Dependence on T cell engagement was greatest at a 1:5 T:B ratio, while cell proliferation and CD38+ signal was greatest at a 1:1 T:B ratio. Furthermore, plasmablast formation was established starting from naïve T and B cells on-chip. We envision that this MPS model of primary lymphocyte physiology will enable new mechanistic analyses of human humoral immunity in vitro.
Stable, Easy-to-Handle, Fully Autologous Electrospun Polymer-Peptide Skin Equivalent for Severe Burn Injuries
Authors: Cohen-Gerassi Dana , BenShoshan Marina , Liiani Adi , Reuveni Tomer , Loboda Offir , Haratz Moti , Haik Josef , Binderman Itzhak , Shacham-Diamand Yosi , Sitt Amit , Segni Ayelet Di , Adler-Abramovich Lihi 
Published: January 2025

AbstractSevere burn injuries represent a significant clinical challenge due to their complex healing process and the high risk of complications, including infection, scarring, and contracture formation. Current therapeutic approaches for burn wound treatment include autologous donor-site grafting and advanced cell therapy techniques like cultured epidermal autografts (CEA), which successfully facilitate wound closure through re-epithelialization. However, CEAs are limited by fragility, shrinkage, lack of a dermal layer, and risks of contamination. Here, aiming to overcome these limitations, we developed a personalized skin equivalent featuring an engineered scaffold composed of electrospun polycaprolactone (PCL) functionalized with the bioactive peptide fluorenylmethyloxycarbonyl-phenylalanine-arginine-glycine-aspartic acid (Fmoc-FRGD). This scaffold is designed to mimic the natural extracellular matrix (ECM), promoting cellular adhesion, integration, and proliferation while maintaining structural integrity.In-vitroanalysis demonstrated the scaffold’s ability to support multi-layered human skin cell growth, whilein-vivoexperiments confirmed its efficacy in facilitating wound closure and full-thickness skin regeneration in a murine model. This bioengineered skin equivalent is mechanically robust, easy to handle, fully autologous and exhibits no contraction, offering a transformative therapeutic alternative for the treatment of severe burn injuries.
Exploring the visual system of the black Grouse (Lyrurus tetrix): Combining experimental and molecular approaches to inform strategies for reducing collisions
Authors: Potier Simon , Lassance Jean-Marc , Blary Constance , Coulombier Justine , Berthillot Sandrine , Dos Santos Virginie , Andraud Christine , Liénard Marjorie A. 
Published: January 2025

AbstractUnderstanding the visual systems of birds can inform conservation efforts and mitigate anthropogenic threats, such as collisions with man-made structures. This study investigates the visual abilities of the black grouse (Lyrurus tetrix), a European mountain bird highly vulnerable to collisions. Using an integrative approach, we assessed key visual components including visual field configuration, spatial resolution, contrast sensitivity, and spectral sensitivity. Behavioral assays revealed that black grouse have an extensive visual field with a wide binocular overlap and minimal blind spots, allowing for efficient predator detection and foraging. However, their spatial resolution and contrast sensitivity are relatively low, consistent with other prey species. Molecular analyses identified four cone opsins (SWS1, SWS2, Rh2, and LW) with spectral sensitivities spanning ultraviolet to long wavelengths (393–546 nm). These findings highlight the black grouse’s ability to detect UV light. Our results emphasize the need for collision mitigation measures tailored to species-specific visual abilities, including diverters designed with enhanced reflectance and increased visibility. This study advances our understanding of avian vision and provides critical insights to guide conservation strategies for reducing bird collisions in alpine habitats.
Characterizing Gene Regulatory Network Ensembles in Kidney Injury and Repair
Authors: Tannenbaum Eitan , Markiewitz Dana , Kalisky Tomer , Kugler Hillel 
Published: January 2025

AbstractThe inference of gene regulatory networks (GRNs) from single-cell RNAseq data allows for mechanistic characterization of the different cell states and their dynamics in complex biological processes. While numerous algorithms have been proposed to infer GRNs from single-cell transcriptomic data, multiple network solutions may explain the same dataset, posing a challenge for biologically meaningful interpretation. Here, we use the Reasoning Engine for Interaction Networks (RE:IN), a computational tool based on formal reasoning, to characterize GRN ensembles in the context of acute kidney injury (AKI). To this end, we applied RE:IN to a single-cell RNAseq dataset from a mouse ischemiareperfusion injury (IRI) model, focusing on distinct proximal tubule cell states related to kidney injury and repair. We first created an Abstract Boolean Net-work (ABN) model for the kidney using RE:IN and synthesized an ensemble of consistent network solutions. Then, we visualized the ensemble in latent space using Principal Components Analysis (PCA) and discovered four distinct GRN families compatible with the input gene expression and regulatory constraints. Finally, we identified two specific network substructures that discern between the four different network families. This study provides a methodology for characterizing and interpreting GRN heterogeneity in complex processes such as tissue development, disease, and repair.
Make it grow,Pseudozyma aphidisextract promotes plant growth
Authors: Fennec Anton , Rotem Neta , Levy Maggie 
Published: January 2025

AbstractIncreasing global population demands higher agricultural yield while avoiding the use of harmful products in agriculture. The use of beneficial micro-organisms is an Eco-friendly approach to reduce the use of fertilizers and plant growth promoting (PGP) products. This study is focused on the fungusPseudozyma aphidis (P. aphidis), a yeast like dimorphic fungus beneficial to plants and related to the phytopathogenic fungusUstilago maydisthat causes corn smut disease. Our lab isolated a uniqueP. aphidisstrain (PA12) that has shown significant plant protection and plant growth activity. We extracted and screened the active PGP fraction from PA12, calibrated treatment dosage and application method. Tomato, corn and melon plants treated with PA12 extract exhibited; increased germination, shoot length, biomass and higher yield. Our results demonstrate the potential ofP. aphidisextract application as an eco-friendly PGP agent that can contribute to reduction of harmful agricultural products usage.
Effects of increasing hydrostatic pressures on marine microbial enzymatic activities
Authors: Balmonte John Paul , Arnosti Carol , Bartlett Douglas H. , Caddell Stephanie , Glud Ronnie N. 
Published: January 2025

AbstractHigh hydrostatic pressure is characteristic of the deep ocean and presumed to influence microbial functions and viability. However, marine microbial processes are typically measured only at atmospheric pressure (0.1 MPa), limiting our understanding of pressure effects on the activities of microbes that sink as part of the biological carbon pump as well as those that reside in the deep ocean. To test pressure effects on microbial functions, we measured extracellular enzymatic activities—the first step in organic matter remineralization—of a moderate piezophile (Photobacterium profundum SS9), as well as of microbial communities in waters and sediments from shallow to abyssal (5,500 m) depths and their cell-free enzymes (<0.2 µm). Activities were measured at 0.1-100 MPa to assess the pressure effects across the nearly full range of oceanic depths.P. profundumSS9 enzymes show varying pressure effects, from considerable stimulation at optimal pressure (28 MPa) to near complete inhibition (100 MPa). Pressure effects were measured for diverse protein- and carbohydrate-degrading and phosphorus-acquiring enzymes among pelagic and benthic microbial communities. The most common pressure effect is partial activity reduction, indicating a dampening of the initial step of carbon remineralization at increasing pressures. However, retention of cell-free enzymatic activities at higher pressures was occasionally observed even for enzymes from surface-originating assemblages, indicating functionality down to hadal depths and their potential for piezotolerance. These variable pressure effects must be considered when quantifying degradation rates of sinking and deposited particulate matter at increasing pressures in the deep ocean.
Global extent and change in human modification of terrestrial ecosystems from 1990 to 2022
Authors: Theobald David M. , Oakleaf James R. , Moncrieff Glenn , Voigt Maria , Kiesecker Joe , Kennedy Christina M. 
Published: January 2025

AbstractHabitat loss and degradation associated with industrial development is the primary threat and dominant driver of biodiversity loss globally. Spatially-explicit datasets that estimate human pressures are essential to understand the extent and rate of anthropogenic impacts on ecosystems and are critical to inform conservation commitments and efforts under the Global Biodiversity Framework. We leveraged the human modification framework to generate comprehensive, consistent, detailed, robust, temporal, and contemporary datasets to map cumulative and individual threats associated with industrial human activities to terrestrial biodiversity and ecosystems from 1990 to 2022. In ∼2022, 43% of terrestrial lands had very low levels of modification, while 27%, 20%, and 10% had low, moderate, and high modification, respectively. Nearly ⅔ of biomes and ½ of ecoregions currently (∼2022) are moderately-modified, and 24% of terrestrial ecosystems (31 M km2) experienced increased modification from 1990 to 2020. About 29% of countries and 31% of ecoregions might also be particularly vulnerable to biodiversity loss given their above-average increased modification and less than 30% protection.
Kinking and buckling instability in growing bacterial chains
Authors: McMahon Sean G. , Neu John C. , Chen Jing 
Published: January 2025

AbstractMany gram-positive bacteria likeBacillus subtilisandClostridiumspecies, exhibit a growing chain–mediated sliding motility that is driven entirely by the force of cell growth. Particularly, the bacteria maintain cell-cell linkage after cell division and form long chains of many cells. The cells in a chain are continuously pushed outward by the mechanical force of cell growth. As the cell number in a chain grows, the cells toward the tip of the chain accelerate, and can in principle reach very high speeds. Although this seems to suggest a highly efficient motility mechanism, recent modeling work predicted mechanical stress builds up in the growing chain and the resulting chain breakage beyond a critical chain length, which ultimately sets a mechanical limitation in the maximum speed of the chain-mediated sliding. In this work we developed models to show that under different conditions the chain can either form sharp kinks or smooth buckles under the increasing stress. This can explain differential behaviors observed in different bacterial species. Our model further predicted how kinking and buckling affect the susceptibility of the chain to breakage. Our model provides a theoretical framework for predicting the dynamics and efficiency of growing chain–mediated bacterial sliding, and suggest cell properties that can optimize sliding efficiency.
A Lung CT Foundation Model Facilitating Disease Diagnosis and Medical Imaging
Authors: Gao Zebin , Zhang Guoxun , Liang Hengrui , Liu Jiaxin , Ma Liangdi , Wang Tianyun , Guo Yanchen , Chen YuJia , Yan Zeping , Chen Xiangru , Guo Yuchen , He Jianxing , Xu Feng , Wong Tien Yin , Dai Qionghai 
Published: January 2025

AbstractThe concomitant development and evolution of lung computed tomography (CT) and artificial intelligence (AI) has allowed non-invasive lung imaging to be a key part of the clinical care of patients with major diseases, such as lung cancer. However, the paucity of labeled lung CT data has limited the training highly efficacious AI models and thereby has retarded broad-scale adoption and deployment of AI-based lung CT imaging in the real-world clinical setting. In this paper, We introduce LCTfound, a foundational model that encodes images along with correlated clinical information, into a neural network. LCTfound used self-supervised learning pre-trained by diffusion models using a large dataset containing 105,184 lung CT scans (totaling more than 28 million images) from multiple centers. LCTfound was evaluated on 8 categories of lung CT tasks, ranging from scanning-level clinical diagnosis to pixel-level image restoration, including segmentation of mediastinal neoplasm, diagnosis of pulmonary alveolar proteinosis, prognosis of non-small cell lung cancer, prediction of major pathological response to neoadjuvant chemoimmunotherapy, whole lung 3D modeling for surgical navigation, virtual lung computed tomography angiography(CTA), reconstruction of lung CT from sparse views, and enhancement of low-dose CT images. Equipped with the robust few-shot learning capability, LCTfound outperformed the previously state-of-the-art pre-trained models in all the above tasks. LCTfound is a major advancements in self-supervised representation learning on lung CT, laying the groundwork for a foundational model that operates with high efficacy across the spectrum of low-level and high-level clinical tasks and serving a dual purpose in aiding in clinical diagnosis of lung diseases and improving the quality of lung CT imaging.
Predicting Metabolic Dysfunction Associated Steatotic Liver Disease Risk Using Patient-Derived Induced Pluripotent Stem Cells
Authors: Qin Yuanyuan , Chhetri Parth , Theusch Elizabeth , Lim Grace , Teker Sheila , Kuang Yu-Lin , Aziziraftar Shahrbanoo Keshavarz , Mehraban Mohammad Hossein , Munoz-Howell Antonio , Saxena Varun , Le Guillou Dounia , Mattis Aras N. , Maher Jacquelyn J. , Medina Marisa W. 
Published: January 2025

ABSTRACTBackground and AimsMetabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is reversible at early stages, making early identification of high-risk individuals clinically valuable. Previously, we demonstrated that patient-derived induced pluripotent stem cells (iPSCs) harboring MASLD DNA risk variants exhibit greater oleate-induced intracellular lipid accumulation than those without these variants. This study aimed to develop an iPSC-based MASLD risk predictor using functional lipid accumulation assessments.MethodsWe quantified oleate-induced intracellular lipid accumulation in iPSCs derived from three cohorts of diverse ancestry: 1) CIRM cohort (20 biopsy-confirmed MASH cases, 2 biopsy-confirmed MASLD cases, 17 controls), 2) POST cohort (18 MASLD cases, 17 controls), and 3) UCSF cohort (4 biopsy-confirmed MASH cases, 8 controls). Lipid accumulation levels in the CIRM cohort were used to define an iPSC-based MASLD risk score, which was used to predict case/control status in the POST and UCSF cohorts.ResultsIn all three cohorts, lipid accumulation was higher in MASLD/MASH cases vs. controls (CIRM cases vs. controls 3.32 ± 0.25 vs. 2.70 ± 0.19 -fold change, p=0.06; POST cases vs. controls 3.63 ± 0.33 vs. 2.70 ± 0.31, p=0.05; and UCSF cases vs. controls 4.39±0.46 vs. 2.03±0.20, p=0.0002). The iPSC-based MASLD risk score achieved a sensitivity of 44% and specificity of 75% in the POST cohort and 75% and 100%, respectively, in the UCSF cohort. Differences in cohort disease severity and cardiometabolic profiles may explain performance variability.ConclusionWhile validation in larger cohorts is needed, these findings suggest that oleate-induced intracellular lipid accumulation in subject-derived iPSCs is predictive of MASH development. Additional cellular phenotypes and donor information should be explored to improve predictive accuracy to inform MASLD surveillance and prevention strategies.