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Fixational eye movements enhance the precision of visual information transmitted by the primate retina

Nature Communications 2024年第1期15卷 7964页

作者： Wu, Eric G. Brackbill, Nora Rhoades, Colleen Kling, Alexandra Gogliettino, Alex R. Shah, Nishal P. Sher, Alexander Litke, Alan M. Simoncelli, Eero P. Chichilnisky, E.J. Department of Electrical Engineering Stanford University Stanford CA United States Department of Physics Stanford University Stanford CA United States Department of Bioengineering Stanford University Stanford CA United States Department of Neurosurgery Stanford University Stanford CA United States Department of Ophthalmology Stanford University Stanford CA United States Hansen Experimental Physics Laboratory Stanford University 452 Lomita Mall Stanford 94305 CA United States Neurosciences PhD Program Stanford University Stanford CA United States Santa Cruz Institute for Particle Physics University of California Santa Cruz Santa Cruz CA United States Flatiron Institute Simons Foundation New York NY United States Center for Neural Science New York University New York NY United States Courant Institute of Mathematical Sciences New York University New York NY United States

Fixational eye movements alter the number and timing of spikes transmitted from the retina to the brain, but whether these changes enhance or degrade the retinal signal is unclear. To quantify this, we developed a Bayesian method for reconstructing natural images from the recorded spikes of hundreds of retinal ganglion cells (RGCs) in the macaque retina (male), combining a likelihood model for RGC light responses with the natural image prior implicitly embedded in an artificial neural network optimized for denoising. The method matched or surpassed the performance of previous reconstruction algorithms, and provides an interpretable framework for characterizing the retinal signal. Reconstructions were improved with artificial stimulus jitter that emulated fixational eye movements, even when the eye movement trajectory was assumed to be unknown and had to be inferred from retinal spikes. Reconstructions were degraded by small artificial perturbations of spike times, revealing more precise temporal encoding than suggested by previous studies. Finally, reconstructions were substantially degraded when derived from a model that ignored cell-to-cell interactions, indicating the importance of stimulus-evoked correlations. Thus, fixational eye movements enhance the precision of the retinal representation. © The Author(s) 2024.

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Epigenetic factor competition reshapes the EMT landscape

arXiv

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arXiv 2022年

作者： Ali Al-Radhawi, M. Tripathi, Shubham Zhang, Yun Sontag, Eduardo D. Levine, Herbert Department of Electrical and Computer Engineering Northeastern University BostonMA02115 United States Center for Theoretical Biological Physics Northeastern University BostonMA02115 United States PhD Program in Systems Synthetic and Physical Biology Rice University HoustonTX77005 United States Whitehead Institute for Biomedical Research CambridgeMA02142 United States Department of Bioengineering Northeastern University BostonMA02115 United States Department of Physics Northeastern University BostonMA02115 United States Laboratory of Systems Pharmacology Harvard Medical School BostonMA02115 United States State Key Laboratory of Molecular Oncology National Cancer Center National Clinical Research Center for Cancer Cancer Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing100021 China

The emergence of and transitions between distinct phenotypes in isogenic cells can be attributed to the intricate interplay of epigenetic marks, external signals, and gene regulatory elements. These elements include chromatin remodelers, histone modifiers, transcription factors, and regulatory RNAs. Mathematical models known as Gene Regulatory Networks (GRNs) are an increasingly important tool to unravel the workings of such complex networks. In such models, epigenetic factors are usually proposed to act on the chromatin regions directly involved in the expression of relevant genes. However, it has been well-established that these factors operate globally and compete with each other for targets genome-wide. Therefore, a perturbation of the activity of a regulator can redistribute epigenetic marks across the genome and modulate the levels of competing regulators. In this paper, we propose a conceptual and mathematical modeling framework that incorporates both local and global competition effects between antagonistic epigenetic regulators in addition to local transcription factors, and show the counter-intuitive consequences of such interactions. We apply our approach to recent experimental findings on the Epithelial-Mesenchymal Transition (EMT). We show that it can explain the puzzling experimental data as well provide new verifiable predictions. © 2022, CC BY-NC-ND.

关键词： Transcription factors

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Assessment of circulating extracellular vesicles from calorie-restricted mice and humans in ischaemic injury models

Journal of Extracellular Biology

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Journal of Extracellular Biology 2023年第5期2卷 e86页

作者： Jaimes, Manuel S. V. Liao, Chia-Te Chen, Max M. Czosseck, Andreas Lee, Tsung-Lin Chou, Yu-Hsiang Chen, Yung-Ming Lin, Shuei-Liong Lai, James J. Lundy, David J. Graduate Institute of Biomedical Materials & Tissue Engineering Taipei Medical University Taipei Taiwan Division of Nephrology Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei Taiwan Division of Nephrology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan TMU Research Center of Urology and Kidney (TMU-RCUK) Taipei Medical University Taipei Taiwan Division of Nephrology Department of Internal Medicine National Taiwan University Hospital College of Medicine National Taiwan University Taipei Taiwan Graduate Institute of Physiology College of Medicine National Taiwan University Taipei Taiwan Department of Bioengineering University of Washington Seattle WA United States Department of Materials Science and Engineering National Taiwan University of Science and Technology Taipei Taiwan International PhD Program in Biomedical Engineering Taipei Medical University Taipei Taiwan Center for Cell Therapy Taipei Medical University Hospital Taipei Taiwan

Calorie restriction (CR) and fasting affect lifespan, disease susceptibility and response to acute injury across multiple animal models, including ischaemic injuries such as myocardial infarction or kidney hypoxia. The cargo and function of circulating extracellular vesicles (EV) respond to changes in host physiology, including exercise, injury, and other interventions. Thus, we hypothesised that EVs induced following CR may reflect some of the beneficial properties of CR itself. In a pilot study, EVs were isolated from mice following 21 days of 30 % CR, and from eight human donors after 72 h water-only fasting. EV size, concentration and morphology were profiled by NTA, western blot and cryoEM, and their function was assessed using multiple assays related to ischaemic diseases. We found that EVs from post-fasting samples better protected cardiac cells from hypoxia/reperfusion (H/R) injury compared to pre-fasting EVs. However, there was no difference when used to treat H/R-injured kidney epithelial cells. Post-fasting derived EVs slowed the rate of fibroblast migration and slightly reduced macrophage inflammatory gene expression compared to pre-fasting derived EVs. Lastly, we compared miRNA cargos of pre- and post-fasting human serum EVs and found significant changes in a small number of miRNAs. We conclude that fasting appears to influence EV cargo and function, with varied effects worthy of further exploration. © 2023 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

关键词： calorie restriction cardiomyocyte diet extracellular vesicle fasting hypoxia ketone macrophage microRNA serum

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Therapeutic Effect of Ershen Pill (二神丸) Extract on Pi (Spleen)-Shen (Kidney) Yang Deficiency-Induced Diarrhea in Rat Model

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Chinese Journal of Integrative Medicine 2019年第7期25卷 536-542页

作者： PAN Xin XU Kang XIONG Rui CHEN Zhi-min HU Chang-jiang FENG Jian LI Wen-bin College of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu (610075) China College of Pharmacy South Central University for Nationalities Wuhan (430074) China National Innovation and Attracting Talents "111" Base Bioengineering College Chongqing University Chongqing (400030) China University of California Berkeley-Chongqing University Joint PhD. Student Program in Bioengineering Stanley Hall Berkeley CA (94720) United States Key Research Institute of Quality and Efficacy Evaluation of Traditional Chinese Medicine Formula State Administration of Traditional Chinese Medicine Chengdu (610075) China

Objective: To investigate whether Ershen Pill(ESP,二神丸) could alleviate the symptom of Pi(Spleen)-Shen(Kidney) yang deficiency(PSYD)-induced diarrhea in rat model and explore its anti-diarrhea mechanism. Methods: Seventy-five Sprague-Dawley rats were divided into 5 groups by a random number table, including control, positive, model, low-dose(LD) and high-dose(HD) ESP groups, 15 rats in each group. All the rats, except those in the control group, were developed PSYD induced-diarrhea based on its pathology and etiology. The rats in positive, LD and HD ESP groups were treated with Shenling Baizhu Pill(参苓白术丸), LD(1.05 g/kg) or HD(3.50 g/kg) ESP petroleum ether extract once a day for 2 weeks, respectively. Body weight change and diarrhea index were measured. The histology scores of the kidney were evaluated via hematoxylin and eosin(HE) staining. Aquaporin-3(AQP3) expression in the colon was analyzed by immunofluorescence, quantitative reverse transcription-polymerase chain reaction(qRT-PCR) and Western blot, respectively. Results: Compared with the model group, oral administration of LD and HD ESP prevented body weight loss and inhibited diarrhea after 2-week treatment(P<0.05). Kidney deterioration was impeded, and the histology score in LD and HD ESP groups were 8.2 and 10.5, respectively, which were both higher than those in the model group(P<0.05). In addition, ESP treatment alleviated rat colitis, and HD ESP significantly improved the AQP3 positive staining intensity in the colon tissue compared with the model group. The result from Western blot revealed that AQP3 protein synthesis in colon tissue of LD and HD ESP groups increased by 2.1-and 5.9-fold compared with the model group(P<0.05). qR T-PCR result showed that AQP3 gene expression in the HD ESP group was also up-regulated by 2.5-fold normalized to the model group(P<0.05). Conclusion: ESP extract effectively alleviates the symptoms of PSYD and relieves PSYD-induced diarrhea by improving AQP3 synthesis in the col

关键词： Ershen Pill Chinese medicine petroleum ether extract anti-diarrhea AQP3 colon

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Prosthetic hand signals

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Significance 2018年第4期15卷 30-35页

作者： Mike Wininger Reva Johnson PhD has faculty appointments at the University of Hartford (Prosthetics Program) and Yale University (Department of Biostatistics) and is a statistician of clinical trials with the Department of Veterans Affairs. PhD is a professor in the Department of Mechanical Engineering and Bioengineering at Valparaiso University.

How Bayesian inference can decode movement intentions and control the next generation of powered prostheses. By Mike Wininger and Reva Johnson

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Author Correction: Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation

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Nature communications 2024年第1期15卷 7618页

作者： Fan Li Jazlyn Gallego Natasha N Tirko Jenna Greaser Derek Bashe Rudra Patel Eric Shaker Grace E Van Valkenburg Alanoud S Alsubhi Steven Wellman Vanshika Singh Camila Garcia Padilla Kyle W Gheres John I Broussard Roger Bagwell Maureen Mulvihill Takashi D Y Kozai Department of Bioengineering University of Pittsburgh Pittsburgh PA USA. Center for Neural Basis of Cognition Pittsburgh PA USA. Computational Modeling and Simulation PhD Program University of Pittsburgh Pittsburgh PA USA. Department of Biochemistry and Molecular Biology Pennsylvania State University University Park PA USA. Actuated Medical Bellefonte PA USA. Washington University in St. Louis St. Louis MO USA. Department of Neuroscience University of Pittsburgh Pittsburgh PA USA. Columbia University New York NY USA. Department of Bioengineering University of Pittsburgh Pittsburgh PA USA. TK.Kozai@pitt.edu. Center for Neural Basis of Cognition Pittsburgh PA USA. TK.Kozai@pitt.edu. Center for Neuroscience University of Pittsburgh Pittsburgh PA USA. TK.Kozai@pitt.edu. McGowan Institute of Regenerative Medicine University of Pittsburgh Pittsburgh PA USA. TK.Kozai@pitt.edu. NeuroTech Center University of Pittsburgh Brain Institute Pittsburgh PA USA. TK.Kozai@pitt.edu.

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Towards decoding the coupled decision-making of metabolism and epithelial-mesenchymal transition in cancer

arXiv

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arXiv 2020年

作者： Jia, Dongya Park, Jun Hyoung Kaur, Harsimran Jung, Kwang Hwa Yang, Sukjin Tripathi, Shubham Galbraith, Madeline Deng, Youyuan Jolly, Mohit Kumar Kaipparettu, Benny Abraham Onuchic, José N. Levine, Herbert Center for Theoretical Biological Physics Rice University HoustonTX77005 United States Department of Molecular and Human Genetics Baylor College of Medicine HoustonTX77030 United States Centre for BioSystems Science and Engineering Indian Institute of Science BangaloreKarnataka560012 India PhD Program in Systems Synthetic and Physical Biology Rice University HoustonTX77005 United States Department of Physics Northeastern University BostonMA02115 United States Department of Physics and Astronomy Rice University HoustonTX77005 United States Applied Physics Graduate Program Rice University HoustonTX77005 United States Dan L. Duncan Comprehensive Cancer Center Baylor College of Medicine HoustonTX77030 United States Department of Chemistry Rice University HoustonTX77005 United States Department of Biosciences Rice University HoustonTX77005 United States Department of Bioengineering Northeastern University BostonMA02115 United States

Cancer cells have the plasticity to adjust their metabolic phenotypes for survival and metastasis. During metastasis, a developmental program known as the epithelial-mesenchymal transition (EMT) plays a critical role. There is extensive cross-talk between metabolism and EMT, but how this leads to coordinated physiological changes is still uncertain. The elusive connection between metabolism and EMT compromises the efficacy of metabolic therapies targeting metastasis. In this review, we aim for clarifying causation between metabolism and EMT based on recent experimental studies and propose integrated theoretical-experimental efforts to better understand the coupled decision-making of metabolism and EMT. © 2020, CC-BY-NC-ND.

关键词： Metabolism

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Publisher Correction: Immune landscape in invasive ductal and lobular breast cancer reveals a divergent macrophage-driven microenvironment

Nature cancer

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Nature cancer 2023年第4期4卷 582页

作者： Sayali Onkar Jian Cui Jian Zou Carly Cardello Anthony R Cillo Mostofa Rafid Uddin April Sagan Marion Joy Hatice U Osmanbeyoglu Katherine L Pogue-Geile Priscilla F McAuliffe Peter C Lucas George C Tseng Adrian V Lee Tullia C Bruno Steffi Oesterreich Dario A A Vignali Department of Immunology University of Pittsburgh School of Medicine Pittsburgh PA USA. Tumor Microenvironment Center UPMC Hillman Cancer Center Pittsburgh PA USA. Graduate Program in Microbiology and Immunology University of Pittsburgh School of Medicine Pittsburgh PA USA. Department of Biostatistics University of Pittsburgh Pittsburgh PA USA. Computational Biology Department Carnegie Mellon University Pittsburgh PA USA. Joint Carnegie Mellon University-University of Pittsburgh PhD Program in Computational Biology Pittsburgh PA USA. Department of Biomedical Informatics University of Pittsburgh Pittsburgh PA USA. UPMC Hillman Cancer Center Pittsburgh PA USA. NSABP Foundation Pittsburgh PA USA. Department of Bioengineering University of Pittsburgh Pittsburgh PA USA. Section of Breast Surgery Division of Surgical Oncology Department of Surgery University of Pittsburgh College of Medicine Magee Women's Hospital of UPMC Pittsburgh PA USA. Women's Cancer Research Center UPMC Hillman Cancer Center Magee-Womens Research Institute University of Pittsburgh Pittsburgh PA USA. Department of Pathology University of Pittsburgh Pittsburgh PA USA. Cancer Biology Program UPMC Hillman Cancer Center Pittsburgh PA USA. Department of Pharmacology and Chemical Biology University of Pittsburgh Pittsburgh PA USA. Cancer Immunology and Immunotherapy Program UPMC Hillman Cancer Center Pittsburgh PA USA. Women's Cancer Research Center UPMC Hillman Cancer Center Magee-Womens Research Institute University of Pittsburgh Pittsburgh PA USA. oesterreichs@upmc.edu. Cancer Biology Program UPMC Hillman Cancer Center Pittsburgh PA USA. oesterreichs@upmc.edu. Department of Pharmacology and Chemical Biology University of Pittsburgh Pittsburgh PA USA. oesterreichs@upmc.edu. Department of Immunology University of Pittsburgh School of Medicine Pittsburgh PA USA. dvignali@pitt.edu. Tumor Microenvironment Center UPMC Hillman Cancer Center Pittsburgh PA USA. dvignali@pi

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Mixed graphical models for causal analysis of multi-modal variables

arXiv

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arXiv 2017年

作者： Sedgewick, Andrew J. Ramsey, Joseph D. Spirtes, Peter Glymour, Clark Benos, Panayiotis V. Department of Computational and Systems Biology University of Pittsburgh School of Medicine PittsburghPA United States Joint Carnegie Mellon University University of Pittsburgh PhD Program in Computational Biology PittsburghPA United States Department of Bioengineering University of Pittsburgh PittsburghPA United States Department of Philosophy Carnegie Mellon University PittsburghPA United States

Graphical causal models are an important tool for knowledge discovery because they can represent both the causal relations between variables and the multivariate probability distributions over the data. Once learned, causal graphs can be used for classification, feature selection and hypothesis generation, while revealing the underlying causal network structure and thus allowing for arbitrary likelihood queries over the data. However, current algorithms for learning sparse directed graphs are generally designed to handle only one type of data (continuous-only or discrete-only), which limits their applicability to a large class of multi-modal biological datasets that include mixed type variables. To address this issue, we developed new methods that modify and combine existing methods for finding undirected graphs with methods for finding directed graphs. These hybrid methods are not only faster, but also perform better than the directed graph estimation methods alone for a variety of parameter settings and data set sizes. Here, we describe a new conditional independence test for learning directed graphs over mixed data types and we compare performances of different graph learning strategies on synthetic data. Copyright © 2017, The Authors. All rights reserved.

关键词： Directed graphs

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The standard genetic code facilitates exploration of the space of functional nucleotide sequences

arXiv

引用

arXiv 2017年

作者： Tripathi, Shubham Deem, Michael W. PhD Program in Systems Synthetic and Physical Biology Rice University HoustonTX77005 United States Center for Theoretical Biological Physics Rice University HoustonTX77005 United States Department of Bioengineering Rice University HoustonTX77005 United States Department of Physics and Astronomy Rice University HoustonTX77005 United States

The standard genetic code is well known to be optimized for minimizing the phenotypic effects of single nucleotide substitutions, a property that was likely selected for during the emergence of a universal code. Given the fitness advantage afforded by high standing genetic diversity in a population in a dynamic environment, it is possible that selection to explore a large fraction of the space of functional proteins also occurred. To determine whether selection for such a property played a role during the emergence of the nearly universal genetic code, we investigated the number of functional variants of the Escherichia coli PhoQ protein explored at different time scales under translation using different genetic codes. We found that the standard genetic code is highly optimal for exploring a large fraction of the space of functional PhoQ variants at intermediate time scales as compared to random codes. Environmental changes, in response to which genetic diversity in a population provides a fitness advantage, are likely to have occurred at these intermediate time scales. Our results indicate that the ability of the standard code to explore a large fraction of the space of functional sequence variants arises from a balance between robustness and flexibility and is largely independent of the property of the standard code to minimize the phenotypic effects of mutations. We propose that selection to explore a large fraction of the functional sequence space while minimizing the phenotypic effects of mutations contributed towards the emergence of the standard code as the universal genetic code. Copyright © 2017, The Authors. All rights reserved.

关键词： Escherichia coli

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