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Calcium-dependent transcriptional changes in human pancreatic islet cells reveal functional diversity in islet cell subtypes

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Diabetologia 2022年第9期65卷 1519-1533页

作者： Ji Soo Yoon Shugo Sasaki Jane Velghe Michelle Y Y Lee Helena Winata Cuilan Nian Francis C Lynn Diabetes Research Group BC Children's Hospital Research Institute Vancouver BC Canada. CELL Graduate Program Faculty of Medicine University of British Columbia Vancouver BC Canada. Department of Surgery Faculty of Medicine University of British Columbia Vancouver BC Canada. Diabetes Research Group BC Children's Hospital Research Institute Vancouver BC Canada. francis.lynn@ubc.ca. Department of Surgery Faculty of Medicine University of British Columbia Vancouver BC Canada. francis.lynn@ubc.ca. School of Biomedical Engineering University of British Columbia Vancouver BC Canada. francis.lynn@ubc.ca.

AIMS/HYPOTHESIS:Pancreatic islets depend on cytosolic calcium (Ca) to trigger the secretion of glucoregulatory hormones and trigger transcriptional regulation of genes important for islet response to stimuli. To date, there has not been an attempt to profile Ca-regulated gene expression in all islet cell types. Our aim was to construct a large single-cell transcriptomic dataset from human islets exposed to conditions that would acutely induce or inhibit intracellular Ca signalling, while preserving biological heterogeneity. METHODS:We exposed intact human islets from three donors to the following conditions: (1) 2.8 mmol/l glucose; (2) 16 mmol/l glucose and 40 mmol/l KCl to maximally stimulate Ca signalling; and (3) 16 mmol/l glucose, 40 mmol/l KCl and 5 mmol/l EGTA (Ca chelator) to inhibit Ca signalling, for 1 h. We sequenced 68,650 cells from all islet cell types, and further subsetted the cells to form an endocrine cell-specific dataset of 59,373 cells expressing INS, GCG, SST or PPY. We compared transcriptomes across conditions to determine the differentially expressed Ca-regulated genes in each endocrine cell type, and in each endocrine cell subcluster of alpha and beta cells. RESULTS:Based on the number of Ca-regulated genes, we found that each alpha and beta cell cluster had a different magnitude of Ca response. We also showed that polyhormonal clusters expressing both INS and GCG, or both INS and SST, are defined by Ca-regulated genes specific to each cluster. Finally, we identified the gene PCDH7 from the beta cell clusters that had the highest number of Ca-regulated genes, and showed that cells expressing cell surface PCDH7 protein have enhanced glucose-stimulated insulin secretory function. CONCLUSIONS/INTERPRETATION:Here we use our large-scale, multi-condition, single-cell dataset to show that human islets have cell-type-specific Ca-regulated gene expression profiles, some of them specific to subpopulations. In our dataset, we identify PCDH7 as a novel m

关键词： Calcium signalling Islet heterogeneity Islets of Langerhans Polyhormonal cells Single-cell RNA sequencing Transcriptional regulation

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Genetics Blood-brain barrier–penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy

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Science Advances 2022年第16期8卷

作者： Zou, Yan Sun, Xinhong Yang, Qingshan Zheng, Meng Shimoni, Olga Ruan, Weimin Wang, Yibin Zhang, Dongya Yin, Jinlong Huang, Xiangang Tao, Wei Park, Jong Bae Liang, Xing-Jie Leong, Kam W. Shi, Bingyang Henan-Macquarie Uni Joint Centre for Biomedical Innovation Academy for Advanced Interdisciplinary Studies Henan Key Laboratory of Brain Targeted Bio-nanomedicine School of Life Sciences Henan University Henan Kaifeng475004 China Macquarie Medical School Faculty of Medicine Health and Human Sciences Macquarie University SydneyNSW2109 Australia Faculty of Science University of Technology Sydney 15 Broadway Ultimo SydneyNSW2007 Australia Center for Nanomedicine Department of Anesthesiology Harvard Medical School 25 Shattuck St. BostonMA02115 United States Department of Cancer Biomedical Science Graduate School of Cancer Science and Policy National Cancer Center Goyang10408 Korea Republic of Center for Excellence in Nanoscience CAS Key Laboratory for Biological Effects of Nano-materials and Nanosafety National Center for Nanoscience and Technology Chinese Academy of Sciences Beijing100190 China Department of Biomedical Engineering Columbia University New YorkNY10032 United States

We designed a unique nanocapsule for efficient single CRISPR-Cas9 capsuling, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for glioblastoma gene therapy. Our CRISPR-Cas9 nanocapsules can be simply fabricated by encapsulating the single Cas9/sgRNA complex within a glutathione-sensitive polymer shell incorporating a dual-action ligand that facilitates BBB penetration, tumor cell targeting, and Cas9/sgRNA selective release. Our encapsulating nanocapsules evidenced promising glioblastoma tissue targeting that led to high PLK1 gene editing efficiency in a brain tumor (up to 38.1%) with negligible (less than 0.5%) off-target gene editing in high-risk tissues. Treatment with nanocapsules extended median survival time (68 days versus 24 days in nonfunctional sgRNA-treated mice). Our new CRISPR-Cas9 delivery system thus addresses various delivery challenges to demonstrate safe and tumor-specific delivery of gene editing Cas9 ribonucleoprotein for improved glioblastoma treatment that may potentially be therapeutically useful in other brain diseases. Copyright © 2022 The Authors, some rights reserved.

关键词： Nanocapsules

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Chronic iEEG recordings and interictal spike rate reveal multiscale temporal modulations in seizure states

arXiv

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arXiv 2022年

作者： Schroeder, Gabrielle M. Karoly, Philippa J. Maturana, Matias Panagiotopoulou, Mariella Taylor, Peter N. Cook, Mark J. Wang, Yujiang Interdisciplinary Computing and Complex BioSystems Group School of Computing Newcastle University Newcastle upon Tyne United Kingdom Graeme Clark Institute St Vincent’s Hospital University of Melbourne MelbourneVIC Australia Department of Biomedical Engineering University of Melbourne MelbourneVIC Australia Seer Medical Pty Ltd MelbourneVIC Australia Faculty of Medical Sciences Newcastle University Newcastle upon Tyne United Kingdom UCL Queen Square Institute of Neurology Queen Square London United Kingdom

Background and Objectives: Many biological processes are modulated by rhythms on circadian and multidien timescales. In focal epilepsy, various seizure features, such as spread and duration, can change from one seizure to the next within the same patient. However, the specific timescales of this variability, as well as the specific seizure characteristics that change over time, are unclear. Methods: Here, in a cross-sectional observational study, we analysed within-patient seizure variability in 10 patients with chronic intracranial EEG recordings (185-767 days of recording time, 57-452 analysed seizures/patient). We characterised the seizure evolutions as sequences of a finite number of patient-specific functional seizure network states (SNSs). We then compared SNS occurrence and duration to (1) time since implantation and (2) patient-specific circadian and multidien cycles in interictal spike rate. Results: In most patients, the occurrence or duration of at least one SNS was associated with the time since implantation. Some patients had one or more SNSs that were associated with phases of circadian and/or multidien spike rate cycles. A given SNS’s occurrence and duration were usually not associated with the same timescale. Discussion: Our results suggest that different time-varying factors modulate within-patient seizure evolutions over multiple timescales, with separate processes modulating a SNS’s occurrence and duration. These findings imply that the development of time-adaptive treatments in epilepsy must account for several separate properties of epileptic seizures, and similar principles likely apply to other neurological conditions. Copyright © 2022, The Authors. All rights reserved.

关键词： Neurology

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Wireless, self‑powered phototrophic algaerobot‑infused nanotherapeutic hydrogels for enhanced diabetic wound healing

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Chemical engineering Journal 2025年 515卷

作者： Huang, Wei-Yung Kang, Jiunn-Horng Chen, Yan-Ting Liang, Jia-Wei Hoai Hoang, Lan Pham Nguyen, Hieu Trung Chuang, Andrew E.-Y. Graduate Institute of Biomedical Materials and Tissue Engineering International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University New Taipei City23561 Taiwan International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei110 Taiwan Department of Physical Medicine and Rehabilitation School of Medicine College of Medicine Taipei Medical University No.250 Wuxing Street Xinyi District Taipei110 Taiwan Department of Physical Medicine and Rehabilitation Taipei Medical University Hospital Taipei110 Taiwan Graduate Institute of Nanomedicine and Medical Engineering College of Biomedical Engineering Taipei Medical University Taipei110 Taiwan Department of Orthopedics and Trauma Faculty of Medicine University of Medicine and Pharmacy at Ho Chi Minh City Ho Chi Minh City700000 Viet Nam Cell Physiology and Molecular Image Research Center Taipei Medical University-Wan Fang Hospital Taipei11696 Taiwan Precision Medicine and Translational Cancer Research Center Taipei Medical University Hospital Taipei11031 Taiwan

Diabetic wounds present a significant clinical challenge due to impaired immunity, hypoxia, poor neovascularization, and chronic inflammation, often resulting in severe complications such as amputation. Conventional therapies, including hyperbaric oxygen, antioxidants, and electrical stimulation, face limitations in delivering sustained and safe oxygen, hydrogen, and electrical stimulation to the wound site. This study introduces a groundbreaking approach by integrating phototrophic algae robots (AR) into a methylcellulose (MC) hydrogel, combined with platelet-derived extracellular vesicles (pEVs) and conductive glycol chitosan-polypyrrole nanoparticles (GCS-PPy NPs), forming a multifunctional composite system (MC-pEV-AR-GCS-PPy NPs). This advanced composite addresses the limitations of traditional treatments by integrating continuous, self-powered hydrogen and oxygen generation, electrical stimulation, and hyperthermia, all triggered by light-activated, electromagnetically driven mechanisms. Photosynthetic algae robots offer a sustainable solution for the generation of hydrogen and oxygen, effectively targeting the prevalent issues of hypoxia and the deficit frequently encountered in diabetic wounds. This innovative approach improves therapeutic outcomes through the integration of electrochemical processes and nanophototherapeutics, creating a multimodal platform. This platform not only promotes tissue regeneration and angiogenesis but also alleviates hypoxic conditions, modulates immune responses, and addresses key challenges associated with chronic wound healing. Incorporating pEVs amplifies the regenerative potential of the system, accelerating wound healing and promoting tissue regeneration. This self-powered platform not only reduces inflammation and suppresses M1 macrophage bioactivity but also regulates immune responses, creating an optimized healing environment. The MC-pEV-AR-GCS-PPy NPs composite represents a promising translational approach to diabetic wo

关键词： Hyperthermia therapy

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Molecular characterization of the complete mitochondrial genome of morotoge shrimpPandalopsis japonica(Decapoda: Pandalidae)

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Mitochondrial DNA Part B 2019年第1期4卷 545-546页

作者： Tae-Ho Yoon Sapto Andriyono Hye-Eun Kang Nack-keun Kim Soo Rin Lee Hyun-Woo Kim Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of Korea Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaDepartment of Marine Fisheries and Marine Faculty Universitas Airlangga Surabaya East Java Indonesia Department of Marine Biology Pukyong National University Busan Republic of Korea Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaDepartment of Marine Biology Pukyong National University Busan Republic of Korea

The complete mitochondrial genome of the morotoge shrimp,Pandalopsis japonicawas determined by the high-throughput sequencing technique. The mitogenome ofP. japonica(15,909 bp) encoded the 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes as well as the non-coding control region (D-Loop). The mitochondrial genome ofP. japonicashowed an identical gene arrangement in its mitochondrial genome to its relative Pandalid shrimps includingP. borealis and P. *** 13 compared mitogenomes within order Suborder Pleocyemata,P. japonicawas most closely related toP. hypsinotuswith 86% sequence identity clustering together with three other shrimps in family Pandalidae.

关键词： High-throughput sequencing Pandalidae mitochondrial genome shrimp East/Japan Sea

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Towards contrast-agnostic soft segmentation of the spinal cord

arXiv

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arXiv 2023年

作者： Bédard, Sandrine Karthik, Enamundram Naga Tsagkas, Charidimos Pravatà, Emanuele Granziera, Cristina Smith, Andrew Weber, Kenneth Arnold Cohen-Adad, Julien NeuroPoly Lab Institute of Biomedical Engineering Polytechnique Montréal MontréalQC Canada Mila - Québec Artificial Intelligence Institute MontréalQC Canada Basel Department of Biomedical Engineering Faculty of Medicine University Hospital Basel University of Basel Basel Switzerland Department of Neurology University Hospital Basel Basel Switzerland University Hospital Basel University of Basel Basel Switzerland Neuroradiology Department Neurocenter of Southern Switzerland Ospedale Regionale di Lugano Lugano Switzerland Department of Physical Medicine Rehabilitation Physical Therapy Program University of Colorado School of Medicine AuroraCO United States Division of Pain Medicine Department of Anesthesiology Perioperative and Pain Medicine Stanford University School of Medicine StanfordCA United States Functional Neuroimaging Unit CRIUGM University of Montreal MontrealQC Canada Centre de recherche du CHU Sainte-Justine Université de Montréal MontréalQC Canada

Spinal cord segmentation is clinically relevant and is notably used to compute spinal cord cross-sectional area (CSA) for the diagnosis and monitoring of cord compression or neurodegenerative diseases such as multiple sclerosis. While several semi and automatic methods exist, one key limitation remains: the segmentation depends on the MRI contrast, resulting in different CSA across contrasts. This is partly due to the varying appearance of the boundary between the spinal cord and the cerebrospinal fluid that depends on the sequence and acquisition parameters. This contrast-sensitive CSA adds variability in multi-center studies where protocols can vary, reducing the sensitivity to detect subtle atrophies. Moreover, existing methods enhance the CSA variability by training one model per contrast, while also producing binary masks that do not account for partial volume effects. In this work, we present a deep learning-based method that produces soft segmentations of the spinal cord that are stable across MRI contrasts. Using the Spine Generic Public Database of healthy participants (n = 267;contrasts = 6), we first generated participant-wise soft ground truth (GT) by averaging the binary segmentations across all 6 contrasts. These soft GT, along with aggressive data augmentation and a regression-based loss function, were then used to train a U-Net model for spinal cord segmentation. We evaluated our model against state-of-the-art methods and performed ablation studies involving different GT mask types, loss functions, contrast-specific models and domain generalization methods. Our results show that using the soft average segmentations along with a regression loss function reduces CSA variability (p © 2023, CC BY.

关键词： Cerebrospinal fluid

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The complete mitochondrial genome of spearnose grenadier,Coelorinchus multispinulosus, Katayama, 1942 (Gadiformes: Macrouridae)

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Mitochondrial DNA Part B 2019年第1期4卷 1123-1124页

作者： Sapto Andriyono Ah-Ran Kim Md. Jobaidul Alam Hyun Park Hyun-Woo Kim Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaFisheries and Marine Faculty Universitas Airlangga Surabaya Indonesia Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of Korea Korea Polar Research Institute Korea Ocean Research and Development Institute Incheon Republic of Korea Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaDepartment of Marine Biology Pukyong National University Busan Republic of Korea

The complete mitochondrial genome ofCoelorinchus multispinulosuswas determined using the MiSeq platform. The mitogenome ofC. multispinulosus(15,937 bp) contained 13 protein-coding genes, 22 tRNAs, two ribosomal RNAs (12S and 16S), and a control region (D-Loop). The G + C content of its mitogenome was 44.69%, which was lower than A + T contents (55.31%). Unusual start codon (GTG) was identified in three protein-coding genes including COX1, ND2, and ND3. Incomplete stop codons (TA–/T–) were shown in six genes including COX1, COX2, COX3, ND3, ND4, and ATP6. Based on the phylogenetic tree with the currently reported mitogenomes in the family Macrouridae,C. multispinulosuswas most closely related toCoelorinchus kishinouyeiwith 85% nucleotide sequence identity.

关键词： Next-generation sequencing Coelorinchus multispinulosus mitochondrial genome deep-sea fish

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The complete mitochondrial genome of black-spot snapper,Lutjanus fulviflamma(Perciformes: Lutjanidae)

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Mitochondrial DNA Part B 2019年第1期4卷 366-367页

作者： Sapto Andriyono Sinar Pagi Sektiana Jobaidul Alam Hyun-Woo Kim Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaDepartment of Marine Fisheries and Marine Faculty Universitas Airlangga C Campus Jl. Mulyorejo Surabaya East Java Surabaya Indonesia Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of Korea Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaDepartment of Marine Biology Pukyong National University Busan Republic of Korea

The complete mitochondrial genome sequence of Dory snapper,Lutjanus fulviflamma,was determined by high-throughput sequencing (HTS) technique. The circular mitogenome ofL. fulviflammawas 16,512bp in length encoding 37 genes (13 proteins, 22 tRNAs, 2 ribosomal RNAs) and 2 conserved noncoding elements; the control region (D-Loop) and the origin of light strand synthesis (OL). Among the protein-coding genes, unusual start codons were identified in ND2, COX1 and ND3 genes and incomplete stop codons were identified in seven genes. Phylogenetic analysis with the currently known mitogenomes in genus Lutjanus revealed thatL. fulviflammawas most closely related toLutjanus russelliiwith 91% sequence identity.

关键词： High-throughput sequencing Lutjanidae mitogenome snapper coral reef

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Benchmarking the Immersed Boundary Method for Viscoelastic Flows

arXiv

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arXiv 2023年

作者： Gruninger, Cole Barrett, Aaron Fang, Fuhui Forest, M. Gregory Griffith, Boyce E. Department of Mathematics University North Carolina Chapel HillNC United States Department of Mathematics University of Utah Salt Lake CityUT United States Department of Applied Physical Sciences University of North Carolina Chapel HillNC United States Department of Biomedical Engineering University of North Carolina Chapel HillNC United States Carolina Center for Interdisciplinary Applied Mathematics University of North Carolina Chapel HillNC United States Computational Medicine Program University of North Carolina School of Medicine Chapel HillNC United States McAllister Heart Institute University of North Carolina School of Medicine Chapel HillNC United States

We present and analyze a series of benchmark tests regarding the application of the immersed boundary (IB) method to viscoelastic flows through and around non-trivial, stationary geometries. The IB method is widely used for the simulation of biological fluid dynamics and other modeling scenarios where a structure is immersed in a fluid. Although the IB method has been most commonly used to model systems with viscous incompressible fluids, it also can be applied to visoelastic fluids, and has enabled the study of a wide variety of dynamical problems including the settling of vesicles and the swimming of elastic filaments in fluids modeled by the Oldroyd-B constuitive equation. However, to date, relatively little work has explored the accuracy or convergence properties of the numerical scheme. Herein, we present benchmarking results for an IB solver applied to viscoelastic flows in and around non-trivial geometries using the idealized Oldroyd-B and more realistic, polymer-entanglement-based Rolie-Poly constitutive equations. We use two-dimensional numerical test cases along with results from rheology experiments to benchmark the IB method and compare it to more complex finite element and finite volume viscoelastic flow solvers. Additionally, we analyze different choices of regularized delta function and relative Lagrangian grid spacings which allow us to identify and recommend the key choices of these numerical parameters depending on the present flow regime. Copyright © 2023, The Authors. All rights reserved.

关键词： Benchmarking

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A Model of Fluid-Structure and Biochemical Interactions for Applications to Subclinical Leaflet Thrombosis

arXiv

引用

arXiv 2022年

作者： Barrett, Aaron Brown, Jordan A. Smith, Margaret Anne Woodward, Andrew Vavalle, John P. Kheradvar, Arash Griffith, Boyce E. Fogelson, Aaron L. Department of Mathematics University of Utah Salt Lake CityUT United States Department of Mathematics University of North Carolina Chapel HillNC United States Advanced Medical Imaging Lab University of North Carolina Medical Center Chapel HillNC United States University of North Carolina School of Medicine Chapel HillNC United States Division of Cardiology Department of Medicine University of North Carolina Chapel HillNC United States Department of Biomedical Engineering University of California Irvine IrvineCA United States Department of Mathematics Applied Physical Sciences and Biomedical Engineering University of North Carolina Chapel HillNC United States Carolina Center for Interdisciplinary Applied Mathematics University of North Carolina Chapel HillNC United States Computational Medicine Program University of North Carolina Chapel HillNC United States McAllister Heart Institute University of North Carolina Chapel HillNC United States Department of Mathematics and Biomedical Engineering University of Utah Salt Lake CityUT United States

Subclinical leaflet thrombosis (SLT) is a potentially serious complication of aortic valve replacement with a bioprosthetic valve in which blood clots form on the replacement valve. SLT is associated with increased risk of transient ischemic attacks and strokes and can progress to clinical leaflet thrombosis. SLT following aortic valve replacement also may be related to subsequent structural valve deterioration, which can impair the durability of the valve replacement. Because of the difficulty in clinical imaging of SLT, models are needed to determine the mechanisms of SLT and could eventually predict which patients will develop SLT. To this end, we develop methods to simulate leaflet thrombosis that combine fluid-structure interaction and a simplified thrombosis model that allows for deposition along the moving leaflets. Additionally, this model can be adapted to model deposition or absorption along other moving boundaries. We present convergence results and quantify the model's ability to realize changes in valve opening and pressures. These new approaches are an important advancement in our tools for modeling thrombosis in which they incorporate both adhesion to the surface of the moving leaflets and feedback to the fluid-structure interaction. © 2022, CC BY-SA.

关键词： Deposition

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