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arXiv 2020年

作者： Linden, Nathaniel J. Tabuena, Dennis R. Steinmetz, Nicholas A. Moody, William J. Brunton, Steven L. Brunton, Bingni W. Department of Bioengineering University of Washington Seattle United States Department of Biology University of Washington Seattle United States Graduate Program in Neuroscience University of Washington Seattle United States Department of Biological Structure University of Washington Seattle United States Department of Mechanical Engineering University of Washington Seattle United States

Widefield calcium imaging has recently emerged as a powerful experimental technique to record coordinated large-scale brain activity. These measurements present a unique opportunity to characterize spatiotemporally coherent structures that underlie neural activity across many regions of the brain. In this work, we leverage analytic techniques from fluid dynamics to develop a visualization framework that highlights features of flow across the cortex, mapping wave fronts that may be correlated with behavioral events. First, we transform the time series of widefield calcium images into time-varying vector fields using optic flow. Next, we extract concise diagrams summarizing the dynamics, which we refer to as FLOW (flow lines in optical widefield imaging) portraits. These FLOW portraits provide an intuitive map of dynamic calcium activity, including regions of initiation and termination, as well as the direction and extent of activity spread. To extract these structures, we use the finite-time Lyapunov exponent (FTLE) technique developed to analyze time-varying manifolds in unsteady fluids. Importantly, our approach captures coherent structures that are poorly represented by traditional modal decomposition techniques. We demonstrate the application of FLOW portraits on three simple synthetic datasets and two widefield calcium imaging datasets, including cortical waves in the developing mouse and spontaneous cortical activity in an adult mouse. © 2020, CC BY.

关键词： Brain

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V2a interneuron differentiation from mouse and human pluripotent stem cells (vol 74, pg 897, 2019)

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NATURE PROTOCOLS 2020年第1期15卷 181-181页

作者： Butts, Jessica C. Iyer, Nisha White, Nick Thompson, Russell Sakiyama-Elbert, Shelly McDevitt, Todd C. Gladstone Institutes San Francisco USA Graduate Program in Bioengineering University of California San Francisco and University of California Berkeley USA Department of Biomedical Engineering University of Wisconsin–Madison Madison USA Department of Biomedical Engineering University of Texas at Austin Austin USA Department of Biomedical Engineering Washington University in St. Louis St. Louis USA Department of Bioengineering and Therapeutic Sciences University of California San Francisco San Francisco USA

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates

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Cell 2025年

作者： Yan, Xiao Kuster, David Mohanty, Priyesh Nijssen, Jik Pombo-García, Karina Garcia Morato, Jorge Rizuan, Azamat Franzmann, Titus M. Sergeeva, Aleksandra Ly, Anh M. Liu, Feilin Passos, Patricia M. George, Leah Wang, Szu-Huan Shenoy, Jayakrishna Danielson, Helen L. Ozguney, Busra Honigmann, Alf Ayala, Yuna M. Fawzi, Nicolas L. Dickson, Dennis W. Rossoll, Wilfried Mittal, Jeetain Alberti, Simon Hyman, Anthony A. Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) Saxony Dresden 01307 Germany Biotechnology Center (BIOTEC) Center for Molecular and Cellular Bioengineering Technische Universität Dresden Saxony Dresden 01307 Germany Artie McFerrin Department of Chemical Engineering Texas A&M University College Station 77843 TX United States Edward Doisy Department of Biochemistry and Molecular Biology Saint Louis University St. Louis 63104 MO United States Department of Molecular Biology Cell Biology & Biochemistry Brown University Providence 02912 RI United States Center for Biomedical Engineering Brown University Providence 02912 RI United States Department of Chemistry Texas A&M University College Station 77843 TX United States Interdisciplinary Graduate Program in Genetics and Genomics Texas A&M University College Station 77843 TX United States Department of Neuroscience Mayo Clinic Jacksonville 32224 FL United States

Cytosolic aggregation of the nuclear protein TAR DNA-binding protein 43 (TDP-43) is associated with many neurodegenerative diseases, but the triggers for TDP-43 aggregation are still debated. Here, we demonstrate that TDP-43 aggregation requires a double event. One is up-concentration in stress granules beyond a threshold, and the other is oxidative stress. These two events collectively induce intra-condensate demixing, giving rise to a dynamic TDP-43-enriched phase within stress granules, which subsequently transition into pathological aggregates. Intra-condensate demixing of TDP-43 is observed in iPS-motor neurons, a disease mouse model, and patient samples. Mechanistically, intra-condensate demixing is triggered by local unfolding of the RRM1 domain for intermolecular disulfide bond formation and by increased hydrophobic patch interactions in the C-terminal domain. By engineering TDP-43 variants resistant to intra-condensate demixing, we successfully eliminate pathological TDP-43 aggregates in cells. We suggest that up-concentration inside condensates followed by intra-condensate demixing could be a general pathway for protein aggregation. © 2025 The Author(s)

关键词： ALS biomolecular condensate FTD intra-condensate demixing neurodegenerative diseases oxidative stress phase separation protein aggregation stress granules TDP-43

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Author Correction: Multi-institutional atlas of brain metastases informs spatial modeling for precision imaging and personalized therapy

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Nature communications 2025年第1期16卷 5096页

作者： Jorge Barrios Evan Porter Dante P I Capaldi Taman Upadhaya William C Chen Julian R Perks Aditya Apte Michalis Aristophanous Eve LoCastro Dylan Hsu Payton H Stone Javier E Villanueva-Meyer Gilmer Valdes Fei Jiang Michael Maddalena Ase Ballangrud Kayla Prezelski Hui Lin Jinger Y Sun Muhtada A K Aldin Oi Wai Chau Benjamin Ziemer Maasa Seaberg Penny K Sneed Jean L Nakamura Lauren C Boreta Shannon E Fogh David R Raleigh Jessica Chew Harish Vasudevan Soonmee Cha Christopher Hess Ruben Fragoso David B Shultz Luke Pike Shawn L Hervey-Jumper Derek S Tsang Philip Theodosopoulos Daniel Cooke Stanley H Benedict Ke Sheng Jan Seuntjens Catherine Coolens Joseph O Deasy Steve Braunstein Olivier Morin Department of Radiation Oncology University of California San Francisco San Francisco CA USA. Department of Radiation Oncology University of California Davis Health Sacramento CA USA. Department of Radiation Oncology Memorial Sloan Kettering New York NY USA. Department of Medical Physics Memorial Sloan Kettering New York NY USA. Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco CA USA. Department of Neurological Surgery University of California San Francisco San Francisco CA USA. Department of Epidemiology and Biostatistics University of California San Francisco San Francisco CA USA. Moffit Cancer Center Tampa Florida USA. Radiation Medicine Program Princess Margaret Cancer Centre University Health Network Toronto ON Canada. Department of Medical Biophysics University of Toronto Toronto ON Canada. UCSF/UC Berkeley Graduate Program in Bioengineering San Francisco CA USA. Department of Pathology University of California San Francisco San Francisco CA USA. Department of Radiation Oncology University of California San Francisco San Francisco CA USA. Olivier.Morin@ucsf.edu. UCSF/UC Berkeley Graduate Program in Bioengineering San Francisco CA USA. Olivier.Morin@ucsf.edu.

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A Therapist Helping Hand for Walker-Assisted Gait Rehabilitation: A Pre-Clinical Assessment

A Therapist Helping Hand for Walker-Assisted Gait Rehabilita...

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IEEE Colombian Conference on Automatic Control (CCAC)

作者： Sergio D. Sierra M. Mario F. Jimenez Marcela C. Múnera Teodiano Bastos Anselmo Frizera-Neto Carlos A. Cifuentes Department of Biomedical Engineering Julio Garavito Bogotá D.C. Colombia Department of Bioengineering Graduate Program El Bosque University Bogotá D.C. Colombia Graduate Program on of Electrical Engineering Federal University of Espírito Santo Vitoria Brazil

Smart Walkers are robotic devices commonly used to improve physical stability and sensory support for people with lower limb weakness or cognitive impairments. Even though such devices offer continuous monitoring during physical rehabilitation, providing a tool to empower therapists might reduce their efforts and increase patient's safety during gait therapies. The implementation of remote-operation strategies enable therapy managers to remote control and assess the smart walker and user information. In this context, this paper presents a new strategy to control and perceive a walker-assisted gait therapy, by means of a haptic joystick with three operational modes. A set of path following tasks were implemented to validate the operational modes. The kinematic estimation error was calculated, and it was found a decrease in the error, when feedback modes were used. Likewise, results from an usability and acceptance questionnaire show better participant's understating of visual feedback mode, and higher effort perception under haptic feedback mode. This interaction strategy represents a potential joystick application as a safety and control interface in walker-assisted gait.

关键词： Medical treatment Haptic interfaces Safety Usability Robot sensing systems

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Resistive-pulse sensing tumor-derived exosome detection device 22

Resistive-pulse sensing tumor-derived exosome detection devi...

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22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018

作者： Carey, Thomas R. Yu, Connie W. Hall, Jennifer Sohn, Lydia L. UC Berkeley UCSF Graduate Program in Bioengineering United States UC Berkeley Bioengineering United States UC Berkeley Molecular and Cell Biology United States UC Berkeley Mechanical Engineering United States

ISBN: (纸本)9781510897571

We present the theory, design, and proof-of-concept demonstration of a tumor-derived exosome detection platform that enables non-invasive, cost-effective, point-of-care cancer screening. Our platform detects exosomes displaying a specific surface antigen by electronically measuring through node-pore sensing the effective size increase that occurs when exosomes bind to colloids functionalized with specific antibodies. We have demonstrated that our platform can differentially detect exosomes derived from A549 cells (a non-small cell lung cancer cell line) and BEAS-2B cells (a non-malignant bronchial epithelial cell line). Copyright © (2018) by Chemical and Biological Microsystems Society. All rights reserved.

关键词： Tumors

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Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity

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Nanomedicine: Nanotechnology, Biology, and Medicine 2023年 47卷 102628-102628页

作者： Chen, Chia-Hung Weng, Tzu-Han Chuang, Cheng-Hsun Huang, Kai-Yao Huang, Sih-Cheng Chen, Pin-Rong Huang, Hsiao-Hsuan Huang, Ling-Ya Shen, Pei-Chun Chuang, Po-Ya Huang, Hsiao-Yen Wu, Yi-Syuan Chang, Hao-Chiun Weng, Shun-Long Liao, Kuang-Wen Department of Medical Research Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan Dependent of Medical Education MacKay Memorial Hospital Taipei10449 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Industrial Development Graduate Program of College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Medicine MacKay Medical College New Taipei City25245 Taiwan Department of Obstetrics and Gynecology Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan MacKay Junior College of Medicine Nursing and Management Taipei City11260 Taiwan Drug Development and Value Creation Research Center College of Dental Medicine Kaohsiung Medical University School of Dentistry Graduate Institute of Medicine College of Medicine Center for Cancer Research Kaohsiung Medical University Kaohsiung City80708 Taiwan Center for Intelligent Drug Systems and Smart Bio-devices National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biotechnology and Bioindustry Sciences National Cheng Kung University Tainan City70101 Taiwan Ph.D. Degree Program of Biomedical Science and Engineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (DOX) and carrying CpG oligodeoxynucleotide;the transdermally administered nano-liposomal drug complex (LPPC-DOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-DOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-DOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-DOX-CpG. Finally, we have successfully proved transdermal LPPC-DOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor. © 2022

关键词： Tumors

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Accurately predicting anticancer peptide using an ensemble of heterogeneously trained classifiers

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Informatics in Medicine Unlocked 2023年 42卷

作者： Azim, Sayed Mehedi Sabab, Noor Hossain Nuri Noshadi, Iman Alinejad-Rokny, Hamid Sharma, Alok Shatabda, Swakkhar Dehzangi, Iman Center for Computational and Integrative Biology Rutgers University Camden 08102 NJ United States Department of Computer Science and Engineering United International University Plot 2 United City Madani Avenue BaddaDhaka 1212 Bangladesh Department of Bioengineering University of California Riverside 92507 CA United States BioMedical Machine Learning Lab The Graduate School of Biomedical Engineering The University of New South Wales (UNSW Sydney) Sydney NSW 2052 Australia UNSW Data Science Hub UNSW Sydney Sydney NSW 2052 Australia Health Data Analytics Program AI-enabled Processes Research Centre Macquarie University Sydney 2109 Australia Institute for Integrated and Intelligent Systems Griffith University Brisbane Australia Laboratory for Medical Science Mathematics RIKEN Center for Integrative Medical Sciences Yokohama 230-0045 Japan Department of Computer Science Rutgers University Camden 08102 NJ United States

The use of therapeutic peptides for the treatment of cancer has received tremendous attention in recent years. Anticancer peptides (ACPs) are considered new anticancer drugs which have several advantages over chemistry-based drugs including high specificity, strong tumor penetration capacity, and low toxicity level for normal cells. Due to the rise of experimentally verified bioactive peptides, several in silico approaches became imperative for the investigation of the characteristics of ACPs. In this paper, we proposed a new machine learning tool named iACP-RF that uses a combination of several sequence-based features and an ensemble of three heterogeneously trained Random Forest classifiers to accurately predict anticancer peptides. Experimental results show that our proposed model achieves an accuracy of 75.9% which outperforms other state-of-the-art methods by a significant margin. We also achieve 0.52, 75.6%, and 76.2% in terms of Matthews Correlation Coefficient (MCC), Sensitivity, and Specificity, respectively. iACP-RF as a standalone tool and its source code are publicly available at: https://***/MLBC-lab/iACP-RF. © 2023 The Authors

关键词： Anticancer peptides Ensemble learning Feature extraction Heterogeneous classifiers Machine learning Random Forest

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Harnessing Biomaterials and the Lymphatic System for Immunomodulation

SSRN

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SSRN 2020年

作者： Alderfer, Laura Hall, Eva Hanjaya-Putra, Donny Bioengineering Graduate Program University of Notre Dame Notre DameIN46556 United States Aerospace and Mechanical Engineering University of Notre Dame Notre DameIN46556 United States Harper Cancer Research Institute University of Notre Dame Notre DameIN46556 United States Chemical and Biomolecular Engineering University of Notre Dame Notre DameIN46556 United States

The lymphatic system plays an integral part in regulating immune cells trafficking and the transport of macromolecules. However, its influence on disease progression and drug uptake is understood less than the vascular system. To bridge the knowledge gap, biomaterials can be used to investigate the lymphatic system and to provide novel understanding into complex disease states, including cancer metastasis and inflammatory diseases. Insight gained from these mechanistic studies, can be further used to design innovative biomaterials to modulate the immune system, improve drug delivery, and promote tissue regeneration. This review article focuses on recent progresses in (i) biomaterials used for lymphatic vessel formation, (ii) lymphatic models for studying lymphatic-immune cells interactions, (iii) pharmaceuticals and their interactions with the lymphatic system, (iv) drug screening, and (v) disease prediction. Finally, a number of challenges in adopting biomaterials for immunomodulation and future perspectives are discussed. © 2020, The Authors. All rights reserved.

关键词： Immune system

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Enhanced BMP signaling via ALK2 in osteoclasts decreases bone density in mice

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Biochemical and Biophysical Research Communications 2025年 777卷

作者： Hiroyuki Yamaguchi Yolanda V. Gutierrez Maryam Faisal Yuta Nakai Lauren T. Tran Baohong Zhao Yuji Mishina Yoshihiro Komatsu Department of Pediatrics McGovern Medical School The University of Texas Health Science Center at Houston Houston TX 77030 USA University of Texas Rio Grande Valley School of Medicine Edinburg TX 78539 USA Department of Bioengineering Rice University George R. Brown School of Engineering and Computing 77005 Houston TX USA Department of Diagnostic and Biomedical Science The University of Texas Health Science Center at Houston School of Dentistry Houston TX 77054 USA Arthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center Hospital for Special Surgery New York NY 10021 USA Department of Medicine Weill Cornell Medical College New York NY 10065 USA Department of Biologic and Materials Sciences & Prosthodontics School of Dentistry University of Michigan Ann Arbor MI 48109 USA Graduate Program in Genetics and Epigenetics The University of Texas Graduate School of Biomedical Sciences at Houston Houston TX 77030 USA

Bone remodeling is a critical biological process required for bone homeostasis. Osteoclasts are essential skeletal cells for bone resorption, and pathological activation of osteoclastogenesis results in bone volume loss. A prior study suggests that bone morphogenetic protein (BMP) signaling via one of the BMP type I receptors, ALK2, positively regulates osteoclastogenesis in vitro . However, the mechanisms of how the activation of BMP signaling affects osteoclastogenesis in vivo remain elusive. To address this question, we utilized two osteoclast-specific Cre mice, Lysosome 2 ( LysM)-Cre mice and Cathepsin K (Ctsk)-Cre , that enabled us to activate BMP signaling in osteoclast progenitors and/or mature osteoclasts, respectively. We then investigated the effect of osteoclast lineage-specific upregulation of BMP signaling via ALK2 by crossing constitutively active ALK2 ( ca-Alk2 ) mice (hereafter ca-Alk2:LysM-Cre and ca-Alk2:Ctsk-Cre ). Compared with controls, ca-Alk2:LysM-Cre and ca-Alk2:Ctsk-Cre mice displayed osteopenic phenotypes. While the number of RUNX2-positive osteoblasts was unchanged, we found the number of tartrate-resistant acid phosphatase (TRAP)- and CTSK-positive cells in the femur was significantly increased in both ca-Alk2:Ctsk-Cre and ca-Alk2:LysM-Cre mice. Our study suggests that enhanced BMP signaling in osteoclasts promotes osteoclastogenesis in an osteoclast-autonomous manner, leading to reduced bone volume in mice.

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