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Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism

细胞研究（英文版） 2018年第6期28卷 616-624页

作者： Ying Yang Phillip J.Hsu Yu-Sheng Chen Yun-Gui Yang CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and Development College of Future Technology Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China Institute of Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China Department of Chemistry and Institute for Biophysical Dynamics Howard Hughes Medical Institute The University of Chicago Chicago IL 60637 USA Medical Scientist Training Program/Committee on Immunology The University of Chicago Chicago IL 60637 USA CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and Development College of Future Technology Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China

N6-methyladenosine (m6A) is a chemical modification present in multiple RNA species,being most abundant in *** on enzymes or factors that catalyze,recognize,and remove m6A have revealed its comprehensive roles in almost every aspect of mRNA metabolism,as well as in a variety of physiological *** review describes the current understanding of the m6A modification,particularly the functions of its writers,erasers,readers in RNA metabolism,with an emphasis on its role in regulating the isoform dosage of mRNAs.

关键词： Methylation analysis RNA modification

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43852 JAK inhibitor safety compared to traditional systemic immunosuppressive therapies

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Journal of the American Academy of Dermatology 2023年第3期89卷 AB60-AB60页

作者： Bunick, Christopher, MD, PhD Daniele, Stefano, PhD Department of Dermatology and Program in Translational Biomedicine Yale University Medical Scientist Training Program Yale School of Medicine

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Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine

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细胞研究（英文版） 2014年第12期24卷 1493-1496页

作者： Tingting Zhu Ian A Roundtree Ping Wang Xiao Wang Li Wang Chang Sun Yuan Tian Fudan University Shanghai Cancer Center Department of Oncology and Institute of Biomedical Sciences and School of Basic Medical SciencesShanghai Medical College of Fudan University Shanghai 200032 China Medical Scientist Training Program and Department of Biochemistry and Molecular Biology The University of Chicago Chicago IL 60637 USA Department of Chemistry and Institute for Biophysical Dynamics The University of Chicago Chicago IL 60637 USA Howard Hughes Medical Institute The University of Chicago Chicago IL 60637 USA

Dear Editor,N6-methyladenosine (m6A) has been demonstrated to be ubiquitous in several types of eukaryotic RNAs,including messenger RNA (mRNA),transfer RNA (tRNA),ribosomal RNA (rRNA),long non-coding RNA (lncRNA),and small nuclear RNA (snRNA) [1].The recent discoveries of RNA m6A methyltransferase complex METTL3/METTL14/WTAP and demethylases FTO and ALKBH5 prove the reversibility of m6A modification [2-6].

关键词： @@

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Updating Clinical Risk Stratification Models Using Rank-Based Compatibility: Approaches for Evaluating and Optimizing Clinician-Model Team Performance

arXiv

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arXiv 2023年

作者： Ötles, Erkin Denton, Brian T. Wiens, Jenna Medical Scientist Training Program University of Michigan Ann ArborMI United States Department of Industrial and Operations Engineering University of Michigan Ann ArborMI United States Division of Computer Science and Engineering University of Michigan Ann ArborMI United States

As data shift or new data become available, updating clinical machine learning models may be necessary to maintain or improve performance over time. However, updating a model can introduce compatibility issues when the behavior of the updated model does not align with user expectations, resulting in poor user-model team performance. Existing compatibility measures depend on model decision thresholds, limiting their applicability in settings where models are used to generate rankings based on estimated risk. To address this limitation, we propose a novel rank-based compatibility measure, CR, and a new loss function that aims to optimize discriminative performance while encouraging good compatibility. Applied to a case study in mortality risk stratification leveraging data from MIMIC, our approach yields more compatible models while maintaining discriminative performance compared to existing model selection techniques, with an increase in CR of 0.019 (95% confidence interval: 0.005, 0.035). This work provides new tools to analyze and update risk stratification models used in clinical care. © 2023, CC BY.

关键词： Risk assessment

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An efficient approximation for the real-time implementation of the Mixture of Trajectory Models decoder

An efficient approximation for the real-time implementation ...

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IEEE Biomedical Circuits and Systems (BIOCAS)

作者： William Bishop Byron M. Yuy Gopal Santhanam Afsheen Afshar Stephen I. Ryu Krishna V. Shenoy The Johns Hopkins University Applied Physics Laboratory Laurel Maryland USA Department of Electrical Engineering Standford University California USA Department of Electrical Engineering Stanford University Stanford California USA Medical Scientist Training Program Stanford University Stanford California Department of Neurosurgery Stanford University Stanford California Neurosciences Program Stanford University Stanford California

The mixture of trajectory models (MTM) decoder has been used to reconstruct arm trajectories from neural activity. While it produces reasonable results, the computational demands of previously published versions may be too high for many real-time systems. We have developed a novel method of approximating the MTM state posteriors that does not require the use of Newtonpsilas method. We show that this method results in only a small decrease in decoding performance yet reduces computational cost by 56.4%. Additionally, an MTM algorithm using this method of approximating the state posteriors produces more accurate decoded trajectories when using small bin sizes than an MTM algorithm using a Gaussian observation model. The more efficient formulation of the MTM algorithm presented here provides an alternative approximation of this algorithm for use on resource constrained embedded systems.

关键词： Decoding Newton method Iterative algorithms Laboratories Physics computing Real time systems Approximation algorithms Biomedical engineering Neurosurgery Educational institutions

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High-Throughput Co-Culture System for Analysis of Spatiotemporal Cell-Cell Signaling

SSRN

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SSRN 2022年

作者： Son, Minjun Wang, Andrew G. Kenna, Emma Tay, Savaş Pritzker School of Molecular Engineering University of Chicago ChicagoIL60637 United States Institute for Genomics and Systems Biology University of Chicago ChicagoIL60637 United States Medical Scientist Training Program University of Chicago ChicagoIL60637 United States

Study of spatial and temporal aspects of signaling between individual cells is essential in understanding development, the immune response, and host-pathogen interactions. We present an automated high-throughput microfluidic platform that chemically stimulates immune cells to initiate cytokine secretion, and controls the formation of signal gradients that activate neighboring cell populations. Furthermore, our system enables controlling the cell type and density based on distance, and retrieval of cells from different regions for gene expression analysis. Our device performs these tasks in 192 independent chambers to simultaneously test different co-culture conditions. We demonstrate these capabilities by creating various cellular communication scenarios between macrophages and fibroblasts in vitro. We find that spatial distribution of macrophages and heterogeneity in cytokine secretion determine spatiotemporal gene expression responses. Furthermore, we describe how gene expression dynamics depend on a cell’s distance from the signaling source. Our device addresses key challenges in the study of cell-to-cell signaling, and provides high-throughput and automated analysis over a wide range of culture conditions. © 2022, The Authors. All rights reserved.

关键词： Macrophages

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SPATIAL CRAVING PATTERNS IN MARIJUANA USERS: INSIGHTS FROM FMRI BRAIN CONNECTIVITY ANALYSIS WITH HIGH-ORDER GRAPH ATTENTION NEURAL NETWORKS

arXiv

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arXiv 2024年

作者： Ding, Jun-En Yang, Shihao Zilverstand, Anna Kulkarni, Kaustubh R. Gu, Xiaosi Liu, Fegn School of Systems and Enterprises Stevens Institute of Technology Hoboken United States Department of Psychiatry and Behavioral Sciences University of Minnesota MinneapolisMN55414 United States Medical Scientist Training Program The Icahn School of Medicine at Mount Sinai NY10027 United States Psychiatry and Neuroscience and directs the Center for Computational Psychiatry at Mount Sinai New York CityNY United States

The excessive consumption of marijuana can induce substantial psychological and social consequences. In this investigation, we propose an elucidative framework termed high-order graph attention neural networks (HOGANN) for the classification of Marijuana addiction, coupled with an analysis of localized brain network communities exhibiting abnormal activities among chronic marijuana users. HOGANN integrates dynamic intrinsic functional brain networks, estimated from functional magnetic resonance imaging (fMRI), using graph attention-based long short-term memory (GAT-LSTM) to capture temporal network dynamics. We employ a high-order attention module for information fusion and message passing among neighboring nodes, enhancing the network community analysis. Our model is validated across two distinct data cohorts, yielding substantially higher classification accuracy than benchmark algorithms. Furthermore, we discern the most pertinent subnetworks and cognitive regions affected by persistent marijuana consumption, indicating adverse effects on functional brain networks, particularly within the dorsal attention and frontoparietal networks. Intriguingly, our model demonstrates superior performance in cohorts exhibiting prolonged dependence, implying that prolonged marijuana usage induces more pronounced alterations in brain networks. The model proficiently identifies craving brain maps, thereby delineating critical brain regions for analysis. © 2024, CC BY.

关键词： Graph neural networks

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Mycotic aneurysm of the left main coronary artery producing acute coronary occlusion and purulent pericarditis

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International Journal of Cardiology 2007年第3期114卷 E81-E82页

作者： Westover, Kenneth Benedick, Bruce Stanford University School of Medicine Medical Scientist Training Program Stanford CA 94305 United States Stanford University School of Medicine Department of Medicine Palo Alto CA 94304 770 Welch Road #100 United States

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Cerebral hemodynamics and pseudo-continuous arterial spin labeling considerations in adults with sickle cell anemia

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NMR in Biomedicine 2017年第2期30卷 101002/nbm3681页

作者： Juttukonda, Meher R. Jordan, Lori C. Gindville, Melissa C. Davis, Larry T. Watchmaker, Jennifer M. Pruthi, Sumit Donahue, Manus J. Department of Radiology and Radiological Sciences Vanderbilt University Medical Center NashvilleTN United States Department of Pediatrics Division of Pediatric Neurology Vanderbilt Medical Center NashvilleTN United States Medical Scientist Training Program Vanderbilt University NashvilleTN United States Department of Neurology Vanderbilt University Medical Center NashvilleTN United States Department of Psychiatry Vanderbilt University Medical Center NashvilleTN United States

Sickle cell anemia (SCA) is a genetic disorder resulting in reduced oxygen carrying capacity and elevated stroke risk. Pseudo-continuous arterial spin labeling (pCASL) measures of cerebral blood flow (CBF) may have relevance for stroke risk assessment;however, the effects of elevated flow velocity and reduced bolus arrival time (BAT) on CBF quantification in SCA patients have not been thoroughly characterized, and pCASL model parameters used in healthy adults are often applied to patients with SCA. Here, cervical arterial flow velocities and pCASL labeling efficiencies were computed in adults with SCA (n = 19) and age- and race-matched controls without sickle trait (n = 7) using pCASL in sequence with phase contrast MR angiography (MRA). Controls (n = 7) and a subgroup of patients (n = 8) also underwent multi-post-labeling-delay pCASL for BAT assessment. Mean flow velocities were elevated in SCA adults (velocity = 28.3 ± 4.1 cm/s) compared with controls (velocity = 24.5 ± 3.8 cm/s), and mean pCASL labeling efficiency (α) was reduced in SCA adults (α = 0.72) relative to controls (α = 0.91). In patients, mean whole-brain CBF from phase contrast MRA was 91.8 ± 18.1 ml/100 g/min, while mean pCASL CBF when assuming a constant labeling efficiency of 0.86 was 75.2 ± 17.3 ml/100 g/min (p 1 variation. In conclusion, BAT variation influences pCASL quantification less than elevated cervical arterial velocity and labeling efficiency variation in SCA adults;thus, a lower labeling efficiency (α = 0.72) or subject-specific labeling efficiency should be incorporated for SCA patients. Copyright © 2017 John Wiley & Sons, Ltd.

关键词： Flow velocity

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Therapeutic Targeting of Follicular Helper T Cells with Chimeric Antigen Receptor-Expressing Natural Killer Cells

SSRN

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SSRN 2019年

作者： Reighard, Seth D. Cranert, Stacey A. Rangel, Kelly M. Ali, Ayad Gyurova, Ivayla E. de la Cruz-Lynch, Arthur T. Tuazon, Jasmine A. Kottyan, Leah C. Smith, David F. Brunner, Hermine I. Waggoner, Stephen N. Center for Autoimmune Genomics & Etiology Cincinnati Children’s Hospital Medical Center Medical Scientist Training Program University of Cincinnati College of Medicine Immunology Graduate Training Program University of Cincinnati College of Medicine Division of Developmental Biology Cincinnati Children’s Hospital Medical Center Pathobiology and Molecular Medicine Graduate Program University of Cincinnati College of Medicine Department of Pediatrics University of Cincinnati College of Medicine Division of Pediatric Otolaryngology - Head & Neck Surgery Cincinnati Children’s Hospital Medical Center Division of Pulmonary and Sleep Medicine Cincinnati Children’s Hospital Medical Center Department of Otolaryngology - Head & Neck Surgery University of Cincinnati College of Medicine Division of Rheumatology Cincinnati Children’s Hospital Medical Center

Follicular helper T cells (TFH) are critical for vaccine and infection elicitation of long-lived humoral immunity, but exaggerated TFH responses can promote autoimmunity and other pathologies. Unfortunately, no clinical interventions are currently available for selective depletion of TFH cells to alleviate these disease conditions. We engineered a novel chimeric antigen receptor (CAR) that facilitates specific targeting of cells highly expressing human programmed cell death protein 1 (PD-1), a cardinal feature of TFH cells. CAR-expressing natural killer (NK) cells robustly degranulate in response to PD-1, resulting in discriminatory elimination of human tonsil TFH cells while sparing other T and B-cell subsets. Given that CAR NK cells are emerging as a safe and effective alternative to CAR T cells in cancer immunotherapy, our results suggest a new, clinically-translatable application of CAR NK cells for selective depletion of pathogenic TFH cells in specific disease states. © 2019, The Authors. All rights reserved.

关键词： Diseases

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