bluuebunny/crossref_metadata_2025_split huggingface dataset:
NLRP3, NLRP6, and NLRP12 are inflammasomes with distinct expression patterns
Authors: Wei Bo , Billman Zachary P. , Nozaki Kengo , Goodridge Helen S. , Miao Edward A. 
Published: February 2024

AbstractInflammasomes are sensors that detect cytosolic microbial molecules or cellular damage, and in response they initiate a form of lytic regulated cell death called pyroptosis. Inflammasomes signal via homotypic protein-protein interactions where CARD or PYD domains are crucial for recruiting downstream partners. Here, we screened these domains from NLR family proteins, and found that the PYD domain of NLRP6 and NLRP12 could activate caspase-1 to induce cleavage of IL-1β and GSDMD. Inflammasome reconstitution verified that full length NLRP6 and NLRP12 formed inflammasomes in vitro, and NLRP6 was more prone to auto-activation. NLRP6 was highly expressed in intestinal epithelial cells (IEC), but not in immune cells. Molecular phylogeny analysis found that NLRP12 was closely related to NLRP3, but the activation mechanisms are different. NLRP3 was highly expressed in monocytes and macrophages, and was modestly but appreciably expressed in neutrophils. In contrast, NLRP12 was specifically expressed in neutrophils and eosinophils, but was not detectable in macrophages. NLRP12 mutations cause a periodic fever syndrome called NLRP12 autoinflammatory disease. We found that several of these patient mutations caused spontaneous activation of caspase-1 in vitro, which likely causes their autoinflammatory disease. Different cell types have unique cellular physiology and structures which could be perturbed by a pathogen, necessitating expression of distinct inflammasome sensors to monitor for signs of infection.
Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis thymoma
Authors: Yasumizu Yoshiaki , Kinoshita Makoto , Zhang Martin Jinye , Motooka Daisuke , Suzuki Koichiro , Okuzaki Daisuke , Nojima Satoshi , Funaki Soichiro , Shintani Yasushi , Ohkura Naganari , Morii Eiichi , Okuno Tatsusada , Mochizuki Hideki 
Published: February 2024

SummaryMyasthenia gravis (MG) is known to be epidemiologically associated with abnormalities of the thymus, an organ that maintains central tolerance. However, due to the complexity of the thymus, specific characteristics related to the pathogenesis of MG remain elusive. In our study, we attempted to narrow down the features associated with MG using spatial transcriptome analysis of thymoma and thymic hyperplasia samples. We found that the majority of thymomas were constituted by the cortical region, whereas the medullary region was localized in comparatively restricted areas. Moreover, the medullary region contained polygenic enrichment, MG-specific germinal center structures, and a supporting immune microenvironment. Additionally, neuromuscular medullary thymic epithelial cells (nmTECs), previously identified as MG-specific autoantigen-producing cells, were situated at the cortico-medullary junction. The immune microenvironment in the medulla was characterized by a specific chemokine pattern and specific immune cells, such asCCR7+migratory dendritic cells (migDCs) and effector regulatory T (Treg) cells. Furthermore, similar germinal center structures and immune microenvironments were observed in the medulla during thymic hyperplasia. This study indicates that the medulla and junction areas are related to the pathology of MG, suggesting that these areas should be the focus of future studies on MG pathogenesis and drug targeting.
Comparison of Machine Leaning Models for Prediction of Acute Pain Severity and On-Treatment Opioid Utilization in Oral Cavity and Oropharyngeal Cancer Patients Receiving Radiation Therapy: Exploratory Analysis from a Large-Scale Retrospective Cohort
Authors: Salama Vivian , Humbert-Vidan Laia , Godinich Brandon , Wahid Kareem A. , ElHabashy Dina M. , Naser Mohamed A. , He Renjie , Mohamed Abdallah S.R. , Sahli Ariana J. , Hutcheson Katherine A. , Gunn Gary Brandon , Rosenthal David I. , Fuller Clifton D. , Moreno Amy C. 
Published: February 2024

AbstractBackgroundAcute pain is a common and debilitating symptom experienced by oral cavity and oropharyngeal cancer (OC/OPC) patients undergoing radiation therapy (RT). Uncontrolled pain can result in opioid overuse and increased risks of long-term opioid dependence. The specific aim of this exploratory analysis was the prediction of severe acute pain and opioid use in the acute on-treatment setting, to develop risk-stratification models for pragmatic clinical trials.Materials and MethodsA retrospective study was conducted on 900 OC/OPC patients treated with RT during 2017 to 2023. Clinical data including demographics, tumor data, pain scores and medication data were extracted from patient records. On-treatment pain intensity scores were assessed using a numeric rating scale (0-none, 10-worst) and total opioid doses were calculated using morphine equivalent daily dose (MEDD) conversion factors. Analgesics efficacy was assessed based on the combined pain intensity and the total required MEDD. ML models, including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), and Gradient Boosting Model (GBM) were developed and validated using ten-fold cross-validation. Performance of models were evaluated using discrimination and calibration metrics. Feature importance was investigated using bootstrap and permutation techniques.ResultsFor predicting acute pain intensity, the GBM demonstrated superior area under the receiver operating curve (AUC) (0.71), recall (0.39), and F1 score (0.48). For predicting the total MEDD, LR outperformed other models in the AUC (0.67). For predicting the analgesics efficacy, SVM achieved the highest specificity (0.97), and best calibration (ECE of 0.06), while RF and GBM achieved the same highest AUC, 0.68. RF model emerged as the best calibrated model with ECE of 0.02 for pain intensity prediction and 0.05 for MEDD prediction. Baseline pain scores and vital signs demonstrated the most contributed features for the different predictive models.ConclusionThese ML models are promising in predicting end-of-treatment acute pain and opioid requirements and analgesics efficacy in OC/OPC patients undergoing RT. Baseline pain score, vital sign changes were identified as crucial predictors. Implementation of these models in clinical practice could facilitate early risk stratification and personalized pain management. Prospective multicentric studies and external validation are essential for further refinement and generalizability.
Prognosis of aneurysmal subarachnoid hemorrhage not altered with transatlantic airplane transfer. A bicentric matched case–control study
Authors: Martino Frédéric , Trainel Milan , Guillaume Jessica , Schaffar Aurélien , Escalard Simon , Pons Adrien , Engrand Nicolas 
Published: February 2024

AbstractBackgroundThe treatment of a ruptured aneurysm, in a center with expertise in aneurysmal subarachnoid hemorrhage (aSAH), is recommended preferably within 24 to 72 hr. We assessed the impact of long-distance aeromedical evacuation in patients presenting aSAH in a remote island without neuro-interventional capacities.MethodsThis was a case–control study of patients with aSAH flown from a French Caribbean island (Guadeloupe) to Paris, France (6750 km), for neuro-interventional and neuro-ICU management and identical patients from the Paris region over a 10-year period (2010 to 2019). The two populations were matched on age, sex, World Federation of Neurological Surgeons score, and Fisher score. The primary outcome was the 1-year modified Rankin Scale (mRS) score divided into two categories: good outcome (mRS 0 to 3) and poor outcome (mRS 4 to 6). A cost study was added.ResultsAmong 128 consecutive aSAH transferred from Guadeloupe, 93 could be matched with 93 patients with aSAH from the Paris area. The median [Q1,Q3] time from diagnosis to securing the aneurysm was 48 hr [30,63] in the Guadeloupe group versus 23 [12,24] in the control group (p<0.001). The rate of good clinical outcome (1-year-mRS ≤ 3) was 75% in the Guadeloupe group and 82% in the control group (p=0.1). The groups did not differ in 1-year mortality (18% vs 14%, p=0.5) and duration of mechanical ventilation. However, Guadeloupe patients more frequently required mechanical ventilation (59% vs 38%, p<0.001) and external ventricular drainage (55% versus 39%, p=0.005) than the control group, although the number of hydrocephalus events did not differ. The additional cost of treating a Guadeloupe patient in mainland France was estimated at 7580 euros, or 17% of the estimated cost in Guadeloupe.ConclusionsLong distance aeromedical evacuation of Guadeloupe patients with aSAH resulted in a 25-hr increase in median embolization time but had no effect on mortality or functional prognosis at 1 year.
First draft genome assembly and characterization of spongeHalisarca dujardiniireveals key components of basement membrane and broad repertoire of aggregation factors
Authors: Borisenko Ilya , Predeus Alexander , Lavrov Andrey , Ereskovsky Alexander 
Published: February 2024

AbstractHow features characteristic of multicellular animals emerged in evolution and how the body plan of particular taxa was shaped are hotspots of modern evolutionary biology. We can get closer to answering them by studying animals that occupy a basal position on the phylogenetic tree, such as sponges (Porifera). We sequenced the genome of the spongeHalisarca dujardiniiusing Oxford Nanopore and Illumina technologies and made an assembly of long reads, followed by polishing with short reads. The resulting assembly had a size of 176 Mb, matching the prediction from the k-mer distribution, and an N50 of about 785 Kb. By analyzing transposable elements in the genomes ofH. dujardiniiand a number of other sponges, we found that a significant portion of the genome (more than half for Demospongiae) is occupied by repeats, most of which are evolutionary young. RNA-seq data were used to predict about 14000 genes in the genome, several times less than in other Demospongiae. By analyzing ortholog groups unique toH. dujardiniiamong sponges and higher invertebrates, we found overrepresented genes related to the extracellular matrix. The extracellular matrix ofH. dujardiniicontains, among others, key basement membrane components such as laminin, nidogen, fibronectin, and collagen IV, for which phylogenetic analysis has confirmed that it belongs to this type of nonfibrillar collagen. In addition, we showed inH. dujardinii14 aggregation factor genes responsible for cell recognition and adhesion. They are organized in a genomic cluster and have at least two types of domains: Calx-beta, responsible for calcium ion binding, and Wreath domain, unique for this type of molecules. Our obtained assembly and annotation will further expand the understanding of genome evolution at the emergence of animal multicellularity, and will serve as a tool to study the regulation of gene expression by modern methods.
Enhancing Plant Photosynthesis using Carbon Dots as Light Converter and Photosensitizer
Authors: Hu Haitao , Cheng Wenbo , Wang Xueyun , Yang Yu , Yu Xuemeng , Ding Jianwei , Lin Yiliang , Zhao Wei , Zhao Qiao , Ledesma-Amaro Rodrigo , Chen Xihan , Liu Junzhong , Yang Chen , Gao Xiang 
Published: February 2024

AbstractImproving photosynthetic efficiency is pivotal for CO2-based biomanufacturing and agriculture purposes. Despite the progress on photosynthetic biohybrids integrating biocatalysts with synthetic materials, nanomaterials with improved optical and photoelectrochemical properties are still needed to increase the energy-conversion efficiency. Here, we present a novel approach using carbon dots (CDs) as both intracellular photosensitizers and light converters for enhancing solar energy utilization in photosynthetic organisms. The CDs were produced from cyanobacterial biomass and used to convert a broad spectrum of solar irradiation to red light. We demonstrated that the nanosized CDs were incorporated into cyanobacterial cells and transferred light-excited electrons into the photosynthetic electron transfer chain. The biohybrids consisting of the CDs andSynechococcus elongatusexhibited increased growth rates, enhanced activities of both photosystems, and accelerated linear electron transport, compared with the cyanobacterial cells only. The supplementation of the CDs increased CO2-fixation rate and CO2-to-glycerol production by 2.4-fold and 2.2-fold, respectively. Furthermore, the CDs were shown to enhance photosynthesis and promote growth ofArabidopsis thaliana. The fresh weight of plant was increased 1.8-fold by CDs addition. These results reveal that simultaneous photosensitization and spectral modification could substantially improve the efficiency of natural photosynthesis. This study presents CDs as an attractive nanomaterial with great application potential in agriculture and solar-powered biomanufacturing.
Probing PAC1 receptor activation across species with an engineered sensor
Authors: Cola Reto B. , Niethammer Salome N. , Rajamannar Preethi , Gresch Andrea , Bhat Musadiq A. , Assoumou Kevin , Williams Elyse , Hauck Patrick , Hartrampf Nina , Benke Dietmar , Stoeber Miriam , Levkowitz Gil , Melzer Sarah , Patriarchi Tommaso 
Published: February 2024

AbstractClass-B1 G protein-coupled receptors (GPCRs) are an important family of clinically relevant drug targets that remain difficult to investigate via high-throughput screening and in animal models. Here, we engineered PAClight1P78A, a novel genetically-encoded sensor based on a class-B1 GPCR (the human PAC1 receptor, hmPAC1R) endowed with high dynamic range (ΔF/F0= 1100%), excellent ligand selectivity and rapid activation kinetics (τON= 1.15 sec). To showcase the utility of this tool for in vitro applications, we thoroughly characterized and compared its expression, brightness and performance between PAClight1P78Atransfected and stably-expressing cells. Demonstrating its use in animal models, we show robust expression and fluorescence responses upon exogenous ligand application ex vivo and in vivo in mice, as well as in living zebrafish larvae. Thus, the new GPCR-based sensor can be used for a wide range of applications across the life sciences empowering both basic research and drug development efforts.
Mutant fate in spatially structured populations on graphs: connecting models to experiments
Authors: Abbara Alia , Pagani Lisa , García-Pareja Celia , Bitbol Anne-Florence 
Published: February 2024

AbstractIn nature, most microbial populations have complex spatial structures that can affect their evolution. Evolutionary graph theory predicts that some spatial structures modelled by placing individuals on the nodes of a graph affect the probability that a mutant will fix. Evolution experiments are beginning to explicitly address the impact of graph structures on mutant fixation. However, the assumptions of evolutionary graph theory differ from the conditions of modern evolution experiments, making the comparison between theory and experiment challenging. Here, we aim to bridge this gap by using our new model of spatially structured populations. This model considers connected subpopulations that lie on the nodes of a graph, and allows asymmetric migrations. It can handle large populations, and explicitly models serial passage events with migrations, thus closely mimicking experimental conditions. We analyze recent experiments in light of this model. We suggest useful parameter regimes for future experiments, and we make quantitative predictions for these experiments. In particular, we propose experiments to directly test our recent prediction that the star graph with asymmetric migrations suppresses natural selection and can accelerate mutant fixation or extinction, compared to a well-mixed population.Author SummaryPredicting how mutations spread through a population and eventually take over is important for understanding evolution. Complex spatial structures are ubiquitous in natural microbial populations, and can impact the fate of mutants. Theoretical models have been developed to describe this effect. They predict that some spatial structures have mutant fixation probabilities that differ from those of well-mixed populations. Experiments are beginning to probe these effects in the laboratory. However, there is a disconnect between models and experiments, because they consider different conditions. In this work, we connect them through a new model that closely matches experimental conditions. We analyze recent experiments and propose new ones that should allow testing the effects of complex population spatial structures on mutant fate.
Substrate stiffness modulates the emergence and magnitude of senescence phenotypes in dermal fibroblasts
Authors: Starich Bartholomew , Yang Fan , Tanrioven Derin , Kung Heng-Chung , Baek Joanne , Nair Praful R. , Kamat Pratik , Macaluso Nico , Eoh Joon , Han Kyu Sang , Gu Luo , Walston Jeremy , Sun Sean , Wu Pei-Hsun , Wirtz Denis , Phillip Jude M. 
Published: February 2024

ABSTRACTCellular senescence is a major driver of aging and disease. Here we show that substrate stiffness modulates the emergence and magnitude of senescence phenotypes after exposure to senescence inducers. Using a primary dermal fibroblast model, we show that decreased substrate stiffness accelerates senescence-associated cell-cycle arrest and regulates the expression of conventional protein-based biomarkers of senescence. We found that the expression of these senescence biomarkers, namely p21WAF1/CIP1and p16INK4aare mechanosensitive and are in-part regulated by myosin contractility through focal adhesion kinase (FAK)-ROCK signaling. Interestingly, at the protein level senescence-induced dermal fibroblasts on soft substrates (0.5 kPa) do not express p21WAF1/CIP1and p16INK4aat comparable levels to induced cells on stiff substrates (4GPa). However, cells expressCDKN1a, CDKN2a,andIL6at the RNA level across both stiff and soft substrates. Moreover, when cells are transferred from soft to stiff substrates, senescent cells recover an elevated expression of p21WAF1/CIP1and p16INK4aat levels comparable to senescence cells on stiff substrates, pointing to a mechanosensitive regulation of the senescence phenotype. Together, our results indicate that the emergent senescence phenotype depends critically on the local mechanical environments of cells and that senescent cells actively respond to changing mechanical cues.
S100A9 Inhibits and Redirects Prion Protein 89-230 Fragment Amyloid Aggregation
Authors: Ziaunys Mantas , Sulskis Darius , Mikalauskaite Kamile , Sakalauskas Andrius , Snieckute Ruta , Smirnovas Vytautas 
Published: February 2024

AbstractProtein aggregation in the form of amyloid fibrils has long been associated with the onset and development of various amyloidoses, including Alzheimer’s, Parkinson’s or prion diseases. Recent studies of their fibril formation process have revealed that amyloidogenic protein cross-interactions may impact aggregation pathways and kinetic parameters, as well as the structure of the resulting aggregates. Despite a growing number of reports exploring this type of interaction, they only cover just a small number of possible amyloidogenic protein pairings. One such pair is between two neurodegeneration-associated proteins: the pro-inflammatory S100A9 and prion protein, which are known to co-localizein vivo. In this study, we examined their cross-interactionin vitroand discovered that the fibrillar form of S100A9 modulated the aggregation pathway of mouse prion protein 89-230 fragment, while non-aggregated S100A9 also significantly inhibited its primary nucleation process. These results complement previous observations of the pro-inflammatory protein’s role in amyloid aggregation and highlight its potential role against neurodegenerative disorders.
One-step N-terminomics based on isolation of protein N-terminal peptides from LysargiNase digests by tip-based strong cation exchange chromatography
Authors: Morikawa Kazuya , Nishida Hiroshi , Imami Koshi , Ishihama Yasushi 
Published: February 2024

AbstractWe have developed a one-step isolation method for protein N-terminal peptides from LysargiNase digests by pipette tip-based strong cation exchange (SCX) chromatography. This CHAMP-N (CHromatographic AMplification of Protein N-terminal peptides) method using disposable and parallel-processable SCX tips instead of conventional HPLC SCX columns facilitates simple, sensitive and high-throughput N-terminomic profiling without sacrificing the high identification numbers and selectivity achieved by the HPLC-based method. By applying the CHAMP-N method to HEK293T cells, we identified novel cleavage sites for signal and transit peptides, and non-canonical translation initiation sites. Finally, for proteome-wide terminomics, we present a simple and comprehensive N-and C-terminomics platform employing three different tip-based approaches, including CHAMP-N, in which protease digestion and one-step isolation by tip LC are commonly used to achieve complementary terminome coverages.
Anti-drift pose tracker (ADPT): A transformer-based network for robust animal pose estimation cross-species
Authors: Tang Guoling , Han Yaning , Sun Xing , Zhang Ruonan , Han Minghu , Liu Quanying , Wei Pengfei 
Published: February 2024

AbstractDeep learning-based methods have advanced animal pose estimation, enhancing accuracy and efficiency in quantifying animal behavior. However, these methods frequently experience tracking drift, where noise-induced jumps in body point estimates compromise reliability. Here, we present the Anti-Drift Pose Tracker (ADPT), a transformer-based tool that mitigates tracking drift in behavioral analysis. Extensive experiments across cross-species datasets—including proprietary mouse and monkey recordings and public Drosophila and macaque datasets—demonstrate that ADPT significantly reduces drift and surpasses existing models like DeepLabCut and SLEAP in accuracy. Moreover, ADPT achieved 93.16% identification accuracy for 10 unmarked mice and 90.36% accuracy for freely interacting unmarked mice, which can be further refined to 99.72%, enhancing both anti-drift performance and pose estimation accuracy in social interactions. With its end-to-end design, ADPT is computationally efficient and suitable for real-time analysis, offering a robust solution for reproducible animal behavior studies. The ADPT code is available athttps://github.com/tangguoling/ADPT.