bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of gene/protein and metabolite multiomics to reveal biomarkers of nickel ion cytotoxicity and the underlying mechanism
Authors: Huang Yan , Zhang Fudan , Zhang Yajing , Chen Rong , Lü Xiaoying 
Published: June 2024

Abstract
Biomarkers have been applied for toxicity assessment of biomaterials due to their advantages. However, research on biomarkers for biomaterials is still in its early stages. There is a lack of integrated analysis in biomarker research based on multiomics studies. Herein, we report a new approach for combining of gene/protein and metabolite multiomics to reveal biomarkers of nickel ion (Ni2+) cytotoxicity and the underlying mechanism. Firstly, differentially expressed genes and proteins were compared to screen gene/protein pairs exhibiting consistent differential expression within the same Ni2+-treated groups. Next, metabolic pathway analysis was carried out to reveal pathways in which gene/protein pairs and metabolites showed upstream and downstream relationships. Important networks composed of gene/protein pairs, metabolites and metabolic pathways and candidate biomarkers were subsequently identified. Through expression level and function validation, the gene/protein/metabolite biomarkers were confirmed, and the underlying mechanism was revealed: Ni2+ influenced the expression of the Rrm2 gene biomarker, which subsequently affected the expression of the RRM2 protein biomarker. These changes in turn impacted the levels of uric acid and uridine metabolite biomarkers, ultimately inhibiting DNA synthesis, suppressing cell proliferation, increasing intracellular ROS levels and reducing ATP content.
Tristetraprolin mediates immune evasion of mycobacterial infection in macrophages
Authors: Wei Jiawei , Ning Huan , Ramos‐Espinosa Octavio , Eickhoff Christopher S. , Hou Rong , Wang Qinghong , Fu Mingui , Liu Ethan Y. , Fan Daping , Hoft Daniel F. , Liu Jianguo 
Published: June 2024

AbstractImmune evasion of Mycobacterium tuberculosis (Mtb) facilitates intracellular bacterial growth. The mechanisms of immune evasion, however, are still not fully understood. In this study, we reveal that tristetraprolin (TTP), one of the best characterized RNA‐binding proteins controlling the stability of targeted mRNAs, mediates innate immune evasion of mycobacteria. We found that TTP knockout mice displayed reduced bacterial burden in the early stage after Mtb aerosol challenge. Macrophages deficient in TTP also showed an inhibition in intracellular mycobacterial growth. Live mycobacteria induced TTP protein expression in macrophages, which was blocked by the mTOR inhibitor rapamycin. Rapamycin and AZD8055 specifically blocked 4EBP1 phosphorylation in infected macrophages and suppressed intracellular BCG growth. Rapamycin promoted TTP protein degradation through the ubiquitination pathway, whereas the proteasome inhibitor MG‐132 blocked rapamycin function and thus stabilized TTP protein. TTP induction suppressed the expression of iNOS/TNF‐α/IL‐12/IL‐23, and weakened protective immune responses in macrophages, whereas rapamycin enhanced the bactericidal effects through TTP inhibition. Moreover, blocking TTP binding increased the expression of TNF‐α and iNOS and suppressed intracellular mycobacterial growth. Overall, our study reveals a novel role for RNA‐binding protein TTP in Mtb immune evasion mechanisms and provides a potential target for host‐directed therapy against tuberculosis (TB).
NRF2-dependent regulation of the prostacyclin receptor PTGIR drives CD8 T cell exhaustion
Authors: Dahabieh Michael S. , DeCamp Lisa M. , Oswald Brandon M. , Kitchen-Goosen Susan M. , Fu Zhen , Vos Matthew , Compton Shelby E. , Longo Joseph , Williams Kelsey S. , Ellis Abigail E. , Johnson Amy , Sodiya Ibukunoluwa , Vincent Michael , Lee Hyoungjoo , Sheldon Ryan D. , Krawczyk Connie M. , Yao Chen , Wu Tuoqi , Jones Russell G. 
Published: June 2024

AbstractThe progressive decline of CD8 T cell effector function—also known as terminal exhaustion—is a major contributor to immune evasion in cancer. Yet, the molecular mechanisms that drive CD8 T cell dysfunction remain poorly understood. Here, we report that the Kelch-like ECH-associated protein 1 (KEAP1)-Nuclear factor erythroid 2-related factor 2 (NRF2) signaling axis, which mediates cellular adaptations to oxidative stress, directly regulates CD8 T cell exhaustion. Transcriptional profiling of dysfunctional CD8 T cells from chronic infection and cancer reveals enrichment of NRF2 activity in terminally exhausted (Texterm) CD8 T cells. Increasing NRF2 activity in CD8 T cells (via conditional deletion of KEAP1) promotes increased glutathione production and antioxidant defense yet accelerates the development of terminally exhausted (PD-1+TIM-3+) CD8 T cells in response to chronic infection or tumor challenge. Mechanistically, we identify PTGIR, a receptor for the circulating eicosanoid prostacyclin, as an NRF2-regulated protein that promotes CD8 T cell dysfunction. Silencing PTGIR expression restores the anti-tumor function of KEAP1-deficient T cells. Moreover, lowering PTGIR expression in CD8 T cells both reduces terminal exhaustion and enhances T cell effector responses (i.e. IFN-γ and granzyme production) to chronic infection and cancer. Together, these results establish the KEAP1-NRF2 axis as a metabolic sensor linking oxidative stress to CD8 T cell dysfunction and identify the prostacyclin receptor PTGIR as an NRF2-regulated immune checkpoint that regulates CD8 T cell fate decisions between effector and exhausted states.One Sentence SummaryThe KEAP1-NRF2 pathway is hyperactivated in terminally exhausted CD8 T cells and drives T cell dysfunction via transcriptional regulation of the prostacyclin receptor,Ptgir.
Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumors
Authors: Hegde Samarth , Giotti Bruno , Soong Brian Y. , Halasz Laszlo , Berichel Jessica Le , Magen Assaf , Kloeckner Benoit , Mattiuz Raphaël , Park Matthew D. , Marks Adam , Belabed Meriem , Hamon Pauline , Chin Theodore , Troncoso Leanna , Lee Juliana J. , Ahimovic Dughan , Bale Michael , Chung Grace , D’souza Darwin , Angeliadis Krista , Dawson Travis , Kim-Schulze Seunghee , Flores Raja M. , Kaufman Andrew J. , Ginhoux Florent , Josefowicz Steven Z. , Ma Sai , Tsankov Alexander M. , Marron Thomas U. , Brown Brian D. , Merad Miriam 
Published: June 2024

ABSTRACTMonocyte–derived macrophages (mo-macs) drive immunosuppression in the tumor microenvironment (TME) and tumor-enhanced myelopoiesis in the bone marrow (BM) fuels these populations. Here, we performed paired transcriptome and chromatin analysis over the continuum of BM myeloid progenitors, circulating monocytes, and tumor-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. Analyzing chromatin accessibility and histone mark changes, we show that lung tumors prime accessibility for Nfe2l2 (NRF2) in BM myeloid progenitors as a cytoprotective response to oxidative stress. NRF2 activity is sustained and increased during monocyte differentiation into mo-macs in the lung TME to regulate oxidative stress, in turn promoting metabolic adaptation, resistance to cell death, and contributing to immunosuppressive phenotype. NRF2 genetic deletion and pharmacological inhibition significantly reduced mo-macs’ survival and immunosuppression in the TME, enabling NK and T cell therapeutic antitumor immunity and synergizing with checkpoint blockade strategies. Altogether, our study identifies a targetable epigenetic node of myeloid progenitor dysregulation that sustains immunoregulatory mo-macs in the TME.
Repetitive Somatosensory Stimulation Shrinks The Body Image
Authors: Azaroual-Sentucq Malika , Macchione Silvia , Miller Luke E. , Koun Eric , Salemme Romeo , Longo Matthew R. , Muret Dollyane , Farnè Alessandro 
Published: June 2024

AbstractCurrent models of mental body representations (MBRs) indicate that tactile inputs feed several of them for different functions, implying that altering tactile inputs may affect MBRs differently. Here we tested this hypothesis by leveraging Repetitive Somatosensory Stimulation (RSS), known to improve tactile perception by modulating primary somatosensory cortex (SI) activity, and measured its effects over thebody image, thebody modeland thesuperficial schemain a randomized sham-controlled, double-blind cross-over study. Results show that RSS affected thebody image, participants perceiving their finger size as being smaller after RSS. While previous work showed increase of finger size perception after tactile anesthesia (Gandevia & Phegan 1999), these findings reveal that tactile inputs can diametrically modulate the body image. In contrast, RSS did not alter thebody modelorsuperficial schema. In addition, we report a novel mislocalization pattern, with a bias towards the middle finger in the distal phalanges that reverses towards the thumb in the proximal phalanx, enriching the known distortions of thesuperficial schema. Overall, these findings provide novel insights into the functional organization of MBRs and their relationships with somatosensory information. Reducing the perceived body size through RSS could be useful in helping treat body image disturbance.
An Investigation of Parameter-Dependent Cell-Type Specific Effects of Transcranial Focused Ultrasound Stimulation Using an Awake Head-Fixed Rodent Model
Authors: Ramachandran Sandhya , Gao Huan , Yttri Eric , Yu Kai , He Bin 
Published: June 2024

AbstractTranscranial focused ultrasound (tFUS) is a promising neuromodulation technique able to target shallow and deep brain structures with high precision. Previous studies have demonstrated that tFUS stimulation responses are both cell-type specific and controllable through altering stimulation parameters. Specifically, tFUS can elicit time-locked neural activity in regular spiking units (RSUs) that is sensitive to increases in pulse repetition frequency (PRF), while time-locked responses are not seen in fast spiking units (FSUs). These findings suggest a unique capability of tFUS to alter circuit network dynamics with cell-type specificity; however, these results could be biased by the use of anesthesia, which significantly modulates neural activities. In this study, we develop an awake head-fixed rat model specifically designed for tFUS study, and address a key question if tFUS still has cell-type specificity under awake conditions. Using this novel animal model, we examined a series of PRFs and burst duty cycles (DCs) to determine their effects on neuronal subpopulations without anesthesia. We conclude that cell-type specific time-locked and delayed responses to tFUS as well as PRF and DC sensitivity are present in the awake animal model and that despite some differences in response, isoflurane anesthesia is not a major confound in studying the cell-type specificity of ultrasound neuromodulation. We further determine that, in an awake, head-fixed setting, the preferred PRF and DC for inducing time-locked excitation with our pulsed tFUS paradigm are 1500 Hz and 60%, respectively.
The DivisionCounter, a method for counting large ranges of cell divisionsin vivo,reveals cell dynamics of leukemic cell killing via CAR-T therapy
Authors: Hustin Lucie S P , Conrad Cecile , Liu Chang , Fuentealba Jaime , Menegatti Silvia , Shneer Seva , Battistella Aude , Tabarin Fanny , Weber Tom S , Amigorena Sebastian , Duffy Ken R , Perié Leïla 
Published: June 2024

AbstractCell division drives multicellular growth and its dysregulation can cause disease. While approximately 44 divisions are needed to produce without death all 1013cells in the human body, current methods are limited to count 10 cell divisionsin vivoacross diverse mammalian cell types. Here we introduce the DivisionCounter, a method to count cell divisionin vivoover large division ranges (∼70 divisions) using an easy fluorescence readout. We demonstrate that the DivisionCounter accurately measures the average cell division count of cells bothin vitroandin vivo. Its use revealed that leukemia tumor division rates are independent of the organ’s specific microenvironment and CAR-T cell treatment, providing an estimate of tumor death ratesin vivo. The DivisionCounter method holds unique potential for quantifying contributions of cell division, death, and migration to the growth of healthy and pathological mammalian tissues.
Computational Models of Age-Associated Cognitive Slowing
Authors: Ahmed Sanya , Lytton William W , Stewart Terrence , Crystal Howard 
Published: June 2024

AbstractBackgroundCognitive slowing accompanies normal aging, yet understanding of the mechanisms of slowing is limited at the network and neuronal level. Relating the pathophysiological factors responsible for cognitive slowing, and interpreting its relationship to working memory, requires multiscale computer modeling.ObjectiveThe aim of this research is to explore multiple mechanisms of cognitive slowing using computational modeling of the cortex to link neuronal activity with cognitive content.MethodWe developed multiscale computer models of a simple cognitive task - Condition 1 of the Stroop recognition task - using the Nengo system, a cognitive simulation environment with a semantic pointer architecture developed to model cognitive tasks using spiking neural networks. We explored how changes associated with aging such as increased input noise, axonal loss, neuronal loss, and feedback would affect the function of the models.ResultsAxonal loss and increased input noise produced profound slowing. High levels of neuronal loss severely impaired memory and paradoxically decreased slowing via the ability to respond more quickly by “releasing” a prior memory. Increased feedback improved memory at the cost of increased slowing.ConclusionOur simulations suggest that significant slowing could be caused by white matter loss (axonal loss) or input signal degradation (which could be caused by visual or other afferent system worsening). As neuronal loss markedly decreased the duration of working memory, we propose that physiological feedback is increased to preserve working memory at the cost of further cognitive slowing.
MAPK14/p38α Shapes the Molecular Landscape of Endometrial Cancer and promotes Tumorigenic Characteristics
Authors: Joseph Sayali , Zhang Xingyuan , Droby Gaith , Wu Di , Bae-Jump Victoria , Lyons Scott , Mordant Angie , Mills Allie , Herring Laura , Rushing Blake , Bowser Jessica , Vaziri Cyrus 
Published: June 2024

AbstractThe molecular underpinnings ofHighGradeEndometrialCarcinoma (HGEC) metastatic growth and survival are poorly understood. Here we show that ascites-derived and primary tumor HGEC cell lines in 3D spheroid culture faithfully recapitulate key features of malignant peritoneal effusion and exhibit fundamentally distinct transcriptomic, proteomic and metabolomic landscapes when compared with conventional 2D monolayers. Using genetic screening platform we identifyMAPK14(which encodes the protein kinase p38α) as a specific requirement for HGEC in spheroid culture.MAPK14/p38α has broad roles in programing the phosphoproteome, transcriptome and metabolome of HGEC spheroids, yet has negligible impact on monolayer cultures.MAPK14promotes tumorigenicityin vivoand is specifically required to sustain a sub-population of spheroid cells that is enriched in cancer stemness markers. Therefore, spheroid growth of HGEC activates unique biological programs, including p38α signaling, that cannot be captured using 2D culture models and are highly relevant to malignant disease pathology.
Mapping Individual Differences in Intermodal Coupling in Neurodevelopment
Authors: Weinstein Sarah M. , Tu Danni , Hu Fengling , Pan Ruyi , Zhang Rongqian , Vandekar Simon N. , Baller Erica B. , Gur Ruben C. , Gur Raquel E. , Alexander-Bloch Aaron F. , Satterthwaite Theodore D. , Park Jun Young 
Published: June 2024

AbstractWithin-individual coupling between measures of brain structure and function evolves in development and may underlie differential risk for neuropsychiatric disorders. Despite increasing interest in the development of structure-function relationships, rigorous methods to quantify and test individual differences in coupling remain nascent. In this article, we explore and address gaps in approaches for testing and spatially localizing individual differences in intermodal coupling. We propose a new method, called CIDeR, which is designed to simultaneously perform hypothesis testing in a way that limits false positive results and improve detection of true positive results. Through a comparison across different approaches to testing individual differences in intermodal coupling, we delineate subtle differences in the hypotheses they test, which may ultimately lead researchers to arrive at different results. Finally, we illustrate the utility of CIDeR in two applications to brain development using data from the Philadelphia Neurodevelopmental Cohort.
Effects of transcranial photobiomodulation on peripheral biomarkers associated with oxidative stress and complex IV activity in the prefrontal cortex in rats subjected to chronic mild stress
Authors: Bortoluzzi Luciana , Colombo Rafael , Pinto Karoline Motta , Viscardi Lucas Henriques , Missiaggia Ricardo , Turella Douglas Jean , Schwantess Lisandra , Salvador Mirian , Branco Catia Santos , Rigotti Marina , Scotton Ellen , Schons Tainá , Ribeiro Silene Bazi , Caldieraro Marco Antonio , Rosa Adriane R 
Published: June 2024

AbstractBackgroundThis study addresses the urgent need for effective alternatives to treat major depressive disorder (MDD) in patients who do not respond to conventional therapies Transcranial photobiomodulation therapy (tPBM) shows promise by enhancing mitochondrial function and reducing oxidative stress, as demonstrated in the chronic mild stress (CMS) rat model.To analyze the impact of tPBM with two wavelengths (red and infrared) on behavioral and biological parameters related to MDD in a CMS model.MethodsMale Wistar rats were subjected to CMS for five weeks and categorized into resilient (CMS-R) and susceptible (CMS-S) groups using the sucrose consumption test (SCT). The CMS-S group received tPBM treatment (600nm and 840nm) for five weeks. Biological measures included lipid damage (TBARS), antioxidant defense (TEAC), mitochondrial complex IV activity (CCO), and nitric oxide (NO) concentration in the prefrontal cortex and blood were measured.ResultsAs expected, post-tPBM treatment (both red and infrared groups) exhibited increased sucrose consumption compared to the sham (Kruskal Wallis chi-squared=26.131; p<0.001). The red and infrared presented higher serum TEAC levels than the sham and control groups, but these effects did not reach statistical significance (p=0.306). In contrast, the red group showed lower peripheral TBARS levels (M = 9.50, SD = 2.87) than the sham group (M = 13.66, SD = 2.20) (p=0.0048); such effect was similar to the control non-stress group. The infrared group showed higher NO levels within the hippocampus than the sham group (Mean = 107.83; SD = 6.48, Dunn Test p = 0.0134) and higher prefrontal CCO activity levels than the red group (p=0.012), which was similar to the control non-stress group.ConclusionsOur study demonstrated that tPBM using both red and infrared wavelengths significantly improved behavioral and biological parameters in the chronic mild stress (CMS) rat model. In particular, tPBM may offer therapeutic benefits by ameliorating oxidative stress and enhancing mitochondrial function, thereby presenting a promising alternative for the management of MDD.
Genomic sequences and annotations of two pseudomonas species isolated from marine and terrestrial habitats
Authors: Manirakiza Eric , Chaumier Timothée , Tirichine Leïla 
Published: June 2024

ABSTRACTHere, we present the complete genome sequences and annotations of two species of thePseudomonasgenus isolated from marine and terrestrial environments. Both genomes and their annotations are available on BacBrowse (https://BacBrowse.univ-nantes.fr). This study will contribute to better understanding of the diversity present within thePseudomonasgenus.
AI-driven mobile application: unraveling students’ motivational feature preferences for reading comprehension
Authors: Chavez Odicar Joice , Palaoag Thelma 
Published: June 2024

PurposeThis study investigates user preferences for motivational features aligned with self-determination theory (SDT), emphasizing autonomy, relatedness, and competency. The study seeks to identify the most appealing and effective motivational features in AI-driven mobile apps for fostering autonomy, promoting relatedness, and enhancing feelings of competency in the context of reading comprehension.Design/methodology/approachEmploying a mixed-methods research design based on the self-determination theory, the study used triangulation of methods to enhance the research findings' quality, completeness, validity, and understanding.FindingsBoth qualitative and quantitative findings showed similarities in the emphasis on personalization, progress tracking, social interaction, gamification, differences in specific feature preferences, and nuanced recommendations, highlighting the importance of a comprehensive and user-centric development approach.Research limitations/implicationsThe study design and sample size might constrain the statistical power and generalizability of the results. The study used a convenience sample of students from one school.Practical implicationsThe synthesis of findings suggests the need for a comprehensive development strategy that incorporates both the commonalities and nuanced recommendations from qualitative and quantitative data. Combining the strengths of both findings, a holistic user-centric approach that integrates personalization, progress tracking, social interaction, and gamification is crucial for effective app development. Recognizing that individual preferences may vary, developers should consider tailoring features to accommodate a range of user needs, as indicated by qualitative and quantitative insights.Originality/valueThis comprehensive approach contributes to advancing knowledge in AI-driven mobile applications and their impact on student motivation and reading comprehension in the Philippine context. Also, it provides valuable insights for designers and developers, contributing to creating engaging and user-friendly platforms that enhance reading comprehension skills.
Robot‐assisted radical cystectomy for bladder cancer after low anterior resection: A case report
Authors: Watanabe Shoutarou , Kobayashi Hiroaki , Hiroe Nao , Iwasawa Tomohiro , Kosugi Michio , Shimizu Masayuki , Ishida Masaru 
Published: June 2024

AbstractRadical cystectomy after low anterior resection is rare, and no cases of robotic surgery have been reported. Cystectomy in patients who have undergone a previous pelvic surgery, whether open or endoscopic, requires caution to avoid damaging other organs due to anatomical changes caused by adhesions in a limited space. Additionally, the curative nature of the treatment must be maintained. We describe a 69‐year‐old man with a history of open low anterior resection for rectal cancer who underwent robot‐assisted radical cystectomy with extracorporeal ileal conduit construction. Although this procedure is challenging, it was performed safely with the collaboration of colorectal surgeons. The patient was discharged without perioperative complications and remained recurrence‐free for 5 years.