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  1. Article ; Online: Real-Time High Throughput Technique to Quantify Neutrophil Extracellular Traps Formation in Human Neutrophils.

    Nakabo, Shuichiro / Kaplan, Mariana J / Gupta, Sarthak

    Journal of visualized experiments : JoVE

    2023  , Issue 202

    Abstract: Neutrophils are myeloid-lineage cells that form a crucial part of the innate immune system. The past decade has revealed additional key roles that neutrophils play in the pathogenesis of cancer, autoimmune diseases, and various acute and chronic ... ...

    Abstract Neutrophils are myeloid-lineage cells that form a crucial part of the innate immune system. The past decade has revealed additional key roles that neutrophils play in the pathogenesis of cancer, autoimmune diseases, and various acute and chronic inflammatory conditions by contributing to the initiation and perpetuation of immune dysregulation through multiple mechanisms, including the formation of neutrophil extracellular traps (NETs), which are structures crucial in antimicrobial defense. Limitations in techniques to quantify NET formation in an unbiased, reproducible, and efficient way have restricted our ability to further understand the role of neutrophils in health and diseases. We describe an automated, real-time, high-throughput method to quantify neutrophils undergoing NET formation using a live cell imaging platform coupled with a membrane permeability-dependent dual-dye approach using two different DNA dyes to image intracellular and extracellular DNA. This methodology is able to help assess neutrophil physiology and test molecules that can target NET formation.
    MeSH term(s) Humans ; Neutrophils ; Extracellular Traps ; Autoimmune Diseases ; Cell Membrane Permeability ; Coloring Agents ; DNA
    Chemical Substances Coloring Agents ; DNA (9007-49-2)
    Language English
    Publishing date 2023-12-01
    Publishing country United States
    Document type Journal Article ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/66051
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: How cells wrap around virus-like particles using extracellular filamentous protein structures.

    Gupta, Sarthak / Santangelo, Christian D / Patteson, Alison E / Schwarz, J M

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Nanoparticles, such as viruses, can enter cells via endocytosis. During endocytosis, the cell surface wraps around the nanoparticle to effectively eat it. Prior focus has been on how nanoparticle size and shape impacts endocytosis. However, inspired by ... ...

    Abstract Nanoparticles, such as viruses, can enter cells via endocytosis. During endocytosis, the cell surface wraps around the nanoparticle to effectively eat it. Prior focus has been on how nanoparticle size and shape impacts endocytosis. However, inspired by the noted presence of extracellular vimentin affecting viral and bacteria uptake, as well as the structure of coronaviruses, we construct a computational model in which
    Language English
    Publishing date 2023-01-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.30.526272
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: How cells wrap around virus-like particles using extracellular filamentous protein structures.

    Gupta, Sarthak / Santangelo, Christian D / Patteson, Alison E / Schwarz, J M

    ArXiv

    2023  

    Abstract: Nanoparticles, such as viruses, can enter cells via endocytosis. During endocytosis, the cell surface wraps around the nanoparticle to effectively eat it. Prior focus has been on how nanoparticle size and shape impacts endocytosis. However, inspired by ... ...

    Abstract Nanoparticles, such as viruses, can enter cells via endocytosis. During endocytosis, the cell surface wraps around the nanoparticle to effectively eat it. Prior focus has been on how nanoparticle size and shape impacts endocytosis. However, inspired by the noted presence of extracellular vimentin affecting viral and bacteria uptake, as well as the structure of coronaviruses, we construct a computational model in which
    Language English
    Publishing date 2023-01-24
    Publishing country United States
    Document type Preprint
    ISSN 2331-8422
    ISSN (online) 2331-8422
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Sulfonated Poly(2,6-dimethyl-1,4-phenylene ether)-Modified Mixed-Matrix Bifunctional Polyelectrolyte Membranes for Long-Run Anthrarufin-Based Redox Flow Batteries.

    Sharma, Jeet / Gupta, Richa / Mishra, Sarthak / Ramanujam, Kothandaraman / Kulshrestha, Vaibhav

    ACS applied materials & interfaces

    2023  Volume 15, Issue 38, Page(s) 44899–44911

    Abstract: The resurgence in designing polyelectrolyte membrane (PEM) materials has propound grid-scale electrochemical energy storage devices. Herein, we report on studies corroborating the synergistic influence of ionic domain microstructure modification and ... ...

    Abstract The resurgence in designing polyelectrolyte membrane (PEM) materials has propound grid-scale electrochemical energy storage devices. Herein, we report on studies corroborating the synergistic influence of ionic domain microstructure modification and intercalation of telechelic bis-piperidinium-functionalized graphene oxide (GO) to fabricate stable bifunctional membranes from sulfonated poly(2,6-dimethyl-1,4-phenylene ether) (sPPE) for efficient anthrarufin-based alkaline redox flow batteries. A critically long-lasting quest on alkaline stability and
    Language English
    Publishing date 2023-09-14
    Publishing country United States
    Document type Journal Article
    ISSN 1944-8252
    ISSN (online) 1944-8252
    DOI 10.1021/acsami.3c08089
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  5. Article ; Online: Icariin prevents methylmercury-induced experimental neurotoxicity

    Sarthak Sharma / Sidharth Mehan / Zuber Khan / Ghanshyam Das Gupta / Acharan S. Narula

    Heliyon, Vol 10, Iss 1, Pp e24050- (2024)

    Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations

    2024  

    Abstract: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg+) is a neurotoxin that induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, ... ...

    Abstract Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg+) is a neurotoxin that induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, degenerating white matter, inducing apoptosis, excitotoxicity, and reducing myelin basic protein (MBP). This study examines the inhibition of SIRT-1 (silence information regulator 1), Nrf-2 (nuclear factor E2-related factor 2), HO-1 (heme oxygenase 1), and TDP-43 (TAR-DNA-binding protein 43) accumulation in the context of ALS, as well as the modulation of these proteins by icariin (15 and 30 mg/kg, orally), a glycoside flavonoid with neuroprotective properties. Neuroprotective icariin activates SIRT-1, Nrf-2, and HO-1, mitigating inflammation and neuronal injury in neurodegenerative disorders. In-vivo and in-silico testing of experimental ALS models confirmed icariin efficacy in modulating these cellular targets. The addition of sirtinol 10 mg/kg, an inhibitor of SIRT-1, helps determine the effectiveness of icariin. In this study, we also examined neurobehavioral, neurochemical, histopathological, and LFB (Luxol fast blue) markers in various biological samples, including Cerebrospinal fluid (CSF), blood plasma, and brain homogenates (Cerebral Cortex, Hippocampus, Striatum, mid-brain, and Cerebellum). These results demonstrate that the administration of icariin ameliorates experimental ALS and that the mechanism underlying these benefits is likely related to regulating the SIRT-1, Nrf-2, and HO-1 signaling pathways.
    Keywords ALS ; Methylmercury ; Demyelination ; Icariin ; Oligodendrocytes ; Neuroinflammation ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
    Subject code 612
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations.

    Sharma, Sarthak / Mehan, Sidharth / Khan, Zuber / Gupta, Ghanshyam Das / Narula, Acharan S

    Heliyon

    2024  Volume 10, Issue 1, Page(s) e24050

    Abstract: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg+) is a neurotoxin that induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, ... ...

    Abstract Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg+) is a neurotoxin that induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, degenerating white matter, inducing apoptosis, excitotoxicity, and reducing myelin basic protein (MBP). This study examines the inhibition of SIRT-1 (silence information regulator 1), Nrf-2 (nuclear factor E2-related factor 2), HO-1 (heme oxygenase 1), and TDP-43 (TAR-DNA-binding protein 43) accumulation in the context of ALS, as well as the modulation of these proteins by icariin (15 and 30 mg/kg, orally), a glycoside flavonoid with neuroprotective properties. Neuroprotective icariin activates SIRT-1, Nrf-2, and HO-1, mitigating inflammation and neuronal injury in neurodegenerative disorders. In-vivo and in-silico testing of experimental ALS models confirmed icariin efficacy in modulating these cellular targets. The addition of sirtinol 10 mg/kg, an inhibitor of SIRT-1, helps determine the effectiveness of icariin. In this study, we also examined neurobehavioral, neurochemical, histopathological, and LFB (Luxol fast blue) markers in various biological samples, including Cerebrospinal fluid (CSF), blood plasma, and brain homogenates (Cerebral Cortex, Hippocampus, Striatum, mid-brain, and Cerebellum). These results demonstrate that the administration of icariin ameliorates experimental ALS and that the mechanism underlying these benefits is likely related to regulating the SIRT-1, Nrf-2, and HO-1 signaling pathways.
    Language English
    Publishing date 2024-01-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2024.e24050
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  7. Article ; Online: Bite of the wolf: innate immune responses propagate autoimmunity in lupus.

    Gupta, Sarthak / Kaplan, Mariana J

    The Journal of clinical investigation

    2021  Volume 131, Issue 3

    Abstract: The etiopathogenesis of systemic lupus erythematosus (SLE), a clinically heterogeneous multisystemic syndrome that derives its name from the initial characterization of facial lesions that resemble the bite of a wolf, is considered a complex, ... ...

    Abstract The etiopathogenesis of systemic lupus erythematosus (SLE), a clinically heterogeneous multisystemic syndrome that derives its name from the initial characterization of facial lesions that resemble the bite of a wolf, is considered a complex, multifactorial interplay between underlying genetic susceptibility factors and the environment. Prominent pathogenic factors include the induction of aberrant cell death pathways coupled with defective cell death clearance mechanisms that promote excessive externalization of modified cellular and nuclear debris with subsequent loss of tolerance to a wide variety of autoantigens and innate and adaptive immune dysregulation. While abnormalities in adaptive immunity are well recognized and are key to the pathogenesis of SLE, recent findings have emphasized fundamental roles of the innate immune system in the initiation and propagation of autoimmunity and the development of organ damage in this disease. This Review focuses on recent discoveries regarding the role of components of the innate immune system, specifically neutrophils and interferons, in promoting various aspects of lupus pathogenesis, with potential implications for novel therapeutic strategies.
    MeSH term(s) Adaptive Immunity ; Animals ; Autoimmunity ; Humans ; Immunity, Innate ; Interferons/immunology ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/pathology ; Neutrophils/immunology ; Neutrophils/pathology
    Chemical Substances Interferons (9008-11-1)
    Language English
    Publishing date 2021-02-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI144918
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  8. Book ; Online: [Re] Double Sampling Randomized Smoothing

    Gupta, Aryan / Gupta, Sarthak / Kumar, Abhay / Dugar, Harsh

    2023  

    Abstract: This paper is a contribution to the reproducibility challenge in the field of machine learning, specifically addressing the issue of certifying the robustness of neural networks (NNs) against adversarial perturbations. The proposed Double Sampling ... ...

    Abstract This paper is a contribution to the reproducibility challenge in the field of machine learning, specifically addressing the issue of certifying the robustness of neural networks (NNs) against adversarial perturbations. The proposed Double Sampling Randomized Smoothing (DSRS) framework overcomes the limitations of existing methods by using an additional smoothing distribution to improve the robustness certification. The paper provides a clear manifestation of DSRS for a generalized family of Gaussian smoothing and a computationally efficient method for implementation. The experiments on MNIST and CIFAR-10 demonstrate the effectiveness of DSRS, consistently certifying larger robust radii compared to other methods. Also various ablations studies are conducted to further analyze the hyperparameters and effect of adversarial training methods on the certified radius by the proposed framework.
    Keywords Computer Science - Machine Learning ; Computer Science - Cryptography and Security ; Mathematics - Statistics Theory
    Subject code 310
    Publishing date 2023-06-27
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Neuromorphic Time-Multiplexed Reservoir Computing With On-the-Fly Weight Generation for Edge Devices.

    Gupta, Sarthak / Chakraborty, Satrajit / Thakur, Chetan Singh

    IEEE transactions on neural networks and learning systems

    2022  Volume 33, Issue 6, Page(s) 2676–2685

    Abstract: The human brain has evolved to perform complex and computationally expensive cognitive tasks, such as audio-visual perception and object detection, with ease. For instance, the brain can recognize speech in different dialects and perform other cognitive ... ...

    Abstract The human brain has evolved to perform complex and computationally expensive cognitive tasks, such as audio-visual perception and object detection, with ease. For instance, the brain can recognize speech in different dialects and perform other cognitive tasks, such as attention, memory, and motor control, with just 20 W of power consumption. Taking inspiration from neural systems, we propose a low-power neuromorphic hardware architecture to perform classification on temporal data at the edge. The proposed architecture uses a neuromorphic cochlea model for feature extraction and reservoir computing (RC) framework as a classifier. In the proposed hardware architecture, the RC framework is modified for on-the-fly generation of reservoir connectivity, along with binary feedforward and reservoir weights. Also, a large reservoir is split into multiple small reservoirs for efficient use of hardware resources. These modifications reduce the computational and memory resources required, thereby resulting in a lower power budget. The proposed classifier is validated for speech and human activity recognition (HAR) tasks. We have prototyped our hardware architecture using Intel's cyclone-10 low-power series field-programmable gate array (FPGA), consuming only 4790 logic elements (LEs) and 34.9-kB memory, making it a perfect candidate for edge computing applications. Moreover, we have implemented a complete system for speech recognition with the feature extraction block (cochlea model) and the proposed classifier, utilizing 15 532 LEs and 38.4-kB memory. By using the proposed idea of multiple small reservoirs along with on-the-fly generation of reservoir binary weights, our architecture can reduce the power consumption and memory requirement by order of magnitude compared to existing FPGA models for speech recognition tasks with similar complexity.
    MeSH term(s) Brain ; Computers ; Neural Networks, Computer
    Language English
    Publishing date 2022-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2162-2388
    ISSN (online) 2162-2388
    DOI 10.1109/TNNLS.2021.3085165
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Quantification of Neutrophils Undergoing NET Formation and Distinguishing Mechanisms of Neutrophil Cell Death by Use of a High-Throughput Method.

    Nakabo, Shuichiro / Kaplan, Mariana J / Gupta, Sarthak

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2543, Page(s) 129–140

    Abstract: Neutrophils, the most abundant white blood cell type in humans, play a crucial role in innate host defenses. Recent studies have revealed additional key roles in the pathogenesis of cancer and autoimmune diseases through multiple mechanisms including the ...

    Abstract Neutrophils, the most abundant white blood cell type in humans, play a crucial role in innate host defenses. Recent studies have revealed additional key roles in the pathogenesis of cancer and autoimmune diseases through multiple mechanisms including the formation of neutrophil extracellular traps (NETs). Further research to expand the understanding of neutrophils' role in health and diseases is limited by lack of techniques to quantify neutrophils undergoing NET formation in an objective, reproducible, and efficient manner. In this chapter, we describe an automated high-throughput method to quantify NETting neutrophils in real time using a two-color, live-content imaging platform, the IncuCyte™S3 (Essen BioScience, Inc.) system, coupled to membrane integrity-dependent dual-dye approach to image intracellular and extracellular DNA. Based on characteristic differences in nuclear morphology and membrane integrity, this method may also be used to distinguish between different types of neutrophil cell death. This platform can help to assess neutrophil physiology and to develop and test therapeutic targets.
    MeSH term(s) Autoimmune Diseases/metabolism ; Cell Death ; DNA/metabolism ; Extracellular Traps/metabolism ; Humans ; Neutrophils/metabolism
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2022-09-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2553-8_11
    Database MEDical Literature Analysis and Retrieval System OnLINE

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