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2025

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Articles 31 - 46 of 46

Full-Text Articles in Cells

Traction Force Microscopy Using An Epifluorescence Microscope: Experimental Considerations And Caveats, Zaria Booth, Mazen Mezher, Rudra Patel, Venkat Maruthamuthu Jan 2025

Traction Force Microscopy Using An Epifluorescence Microscope: Experimental Considerations And Caveats, Zaria Booth, Mazen Mezher, Rudra Patel, Venkat Maruthamuthu

Mechanical & Aerospace Engineering Faculty Publications

Forces exerted by cells due to their internal contractility play fundamental roles in a host of processes, including adhesion, migration, survival and differentiation. Traction force microscopy (TFM) enables the determination of forces exerted by cells or cell collectives on their environment, which is typically taken to be an extra-cellular matrix (ECM)-coated substrate. Sample preparation for TFM involves the plating of cells onto an environment embedded with fiducial markers. The imaging of these fiducial markers in the presence and absence of the cells then enables calculation of the displacement of localized regions of the environment, and, consequently, the spatial distribution of …


Microbial Remodeling Of Gut Tryptophan Metabolism And Indole-3-Lactate Production Regulate Epithelial Barrier Repair And Viral Suppression In Human And Simian Immunodeficiency Virus Infections, Clarissa Santos Rocha, Katie L. Alexander, Carolina Herrera, Mariana G. Weber, Irina Grishina, Lauren A. Hirao, Dylan J. Kramer, Juan Arredondo, Abigail Mende, Katti R. Crakes, Anne N. Fenton, Maria L. Marco, David A. Mills, John C. Kappes, Lesley E. Smythies, Paul Ziprin, Sumathi Sankaran-Walters, Phillip D. Smith, Satya Dandekar Jan 2025

Microbial Remodeling Of Gut Tryptophan Metabolism And Indole-3-Lactate Production Regulate Epithelial Barrier Repair And Viral Suppression In Human And Simian Immunodeficiency Virus Infections, Clarissa Santos Rocha, Katie L. Alexander, Carolina Herrera, Mariana G. Weber, Irina Grishina, Lauren A. Hirao, Dylan J. Kramer, Juan Arredondo, Abigail Mende, Katti R. Crakes, Anne N. Fenton, Maria L. Marco, David A. Mills, John C. Kappes, Lesley E. Smythies, Paul Ziprin, Sumathi Sankaran-Walters, Phillip D. Smith, Satya Dandekar

Department of Obstetrics & Gynecology Faculty Publications

Gut inflammatory diseases cause microbial dysbiosis. Human immunodeficiency virus-1 (HIV) infection disrupts intestinal integrity, subverts repair/renewal pathways, impairs mucosal immunity and propels microbial dysbiosis. However, microbial metabolic mechanisms driving repair mechanisms in virally inflamed gut are not well understood. We investigated the capability and mechanisms of gut microbes to restore epithelial barriers and mucosal immunity in virally inflamed gut by using a multipronged approach: an in vivo simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV/AIDS, ex vivo HIV-exposed human colorectal explants and primary human intestinal epithelial cells. SIV infection reprogrammed tryptophan (TRP) metabolism, increasing kynurenine catabolite levels that are …


Nucleotide-Derived Bacterial Alarmones Attenuate The Induction Of Type-I Interferon Responses In A Murine Macrophage Reporter Cell Line, Ryan P. Kilduff, Erin B. Purcell, Lisa M. Shollenberger Jan 2025

Nucleotide-Derived Bacterial Alarmones Attenuate The Induction Of Type-I Interferon Responses In A Murine Macrophage Reporter Cell Line, Ryan P. Kilduff, Erin B. Purcell, Lisa M. Shollenberger

Chemistry & Biochemistry Faculty Publications

The stringent response is a well-studied phenomenon in many bacterial systems and regulates resource-consuming activities such as transcription, translation, and replication. The stringent response is a well-conserved signaling framework, as are the nucleotide-derived signaling mediators, collectively referred to as (p)ppGpp or as alarmones. There is a wealth of research evaluating nucleotide-derived alarmone signaling in bacterial models, however, their potential to modulate innate immune signaling has not yet been evaluated. Several common pathogen-synthesized molecules, such as lipopolysaccharide (LPS) and cyclic-di-AMP (c-di-AMP), act as pathogen-associated molecular patterns (PAMPs), which are common patterns that alert the innate immune system of bacterial infection. The …


Caveolin-Mediated Endocytosis: Bacterial Pathogen Exploitation And Host-Pathogen Interaction, Dibyasri Barman, Rishi Drolia Jan 2025

Caveolin-Mediated Endocytosis: Bacterial Pathogen Exploitation And Host-Pathogen Interaction, Dibyasri Barman, Rishi Drolia

Biological Sciences Faculty Publications

Within mammalian cells, diverse endocytic mechanisms, including phagocytosis, pinocytosis, and receptor-mediated endocytosis, serve as gateways exploited by many bacterial pathogens and toxins. Among these, caveolae-mediated endocytosis is characterized by lipid-rich caveolae and dimeric caveolin proteins. Caveolae are specialized microdomains on cell surfaces that impact cell signaling. Caveolin proteins facilitate the creation of caveolae and have three members in vertebrates: caveolin-1, caveolin-2, and caveolin-3. Many bacterial pathogens hijack caveolin machinery to invade host cells. For example, the Gram-positive facultative model intracellular bacterial pathogen Listeria monocytogenes exploits caveolin-mediated endocytosis for efficient cellular entry, translocation across the intestinal barrier, and cell–cell spread. Caveolin …


Protonic Capacitor Cell Energetics: Transmembrane-Electrostatically Localized Protons/Cations, James Weifu Lee Jan 2025

Protonic Capacitor Cell Energetics: Transmembrane-Electrostatically Localized Protons/Cations, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

The transmembrane-electrostatically localized protons/cations charges (TELPs/TELCs) theory can serve as a theoretical framework to better explain cell electrophysiology and elucidate bioenergetic systems including both delocalized and localized protonic coupling. According to the TELCs model, the excess positive charges of TELCs at one side of the membrane are balanced by the excess negative charges of transmembrane-electrostatically localized hydroxides anions (TELAs) at the other side of the membrane. Through the TELCs-membrane-TELAs capacitor model, the energetics of oxidative phosphorylation have recently been better elucidated in mitochondria and alkalophilic bacteria, leading to the identification of a novel Type-B energetic process. Both the TELCs model …


Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors, Andrew C. Pearson, Jessica S. Miller, Hannah J. Jensen, Ketan Shrestha, Thomas E. Curry Jr., Diane M. Duffy Jan 2025

Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors, Andrew C. Pearson, Jessica S. Miller, Hannah J. Jensen, Ketan Shrestha, Thomas E. Curry Jr., Diane M. Duffy

Department of Biomedical and Translational Sciences Faculty Publications

Neurotensin (NTS), a small neuropeptide, was recently established as a key paracrine mediator of ovulation. NTS mRNA is highly expressed by granulosa cells in response to the luteinizing hormone (LH) surge, and multiple NTS receptors are expressed by cells of the ovulatory follicle. To identify the role of NTS receptors NTSR1 and SORT1 in ovulation in vivo, the dominant follicle of cynomolgus macaques (Macaca fascicularis) was injected with either vehicle control, the general NTS receptor antagonist SR142948, the NTSR1-selective antagonist SR48692, or the SORT1-selective antagonist AF38469. Human chorionic gonadotropin (hCG) was then administered to initiate ovulatory events. …


Cannabinoid-2 Receptor Activation Attenuates Sulfur Mustard Analog 2-Chloroethyl-Ethyl-Sulfide-Induced Acute Lung Injury In Mice, Gregory Nicholson, Nicholas Richards, Janette Lockett, My Boi Ly, Raj V. Nair, Woong-Ki Kim, K. Yaragudri Vinod, Nagaraja Nagre Jan 2025

Cannabinoid-2 Receptor Activation Attenuates Sulfur Mustard Analog 2-Chloroethyl-Ethyl-Sulfide-Induced Acute Lung Injury In Mice, Gregory Nicholson, Nicholas Richards, Janette Lockett, My Boi Ly, Raj V. Nair, Woong-Ki Kim, K. Yaragudri Vinod, Nagaraja Nagre

Department of Biomedical and Translational Sciences Faculty Publications

Background: Exposure to sulfur mustard (SM; 2,2′-dichlorodiethyl sulfide) causes toxicity in the human body, particularly the lungs. The molecular mechanisms of SM-induced lung damage are elusive, and no effective treatments exist. This study explores the anti-inflammatory potential of cannabinoid receptor 2 (CB2R) activation in mitigating acute lung injury (ALI) and inflammation induced by 2-chloroethyl ethyl sulfide (CEES), a structural analog of SM. Methods: C57BL/6J mice were exposed to CEES via intratracheal administration to model ALI. CB2R activation was achieved through the intraperitoneal administration of HU308, a selective synthetic agonist. ALI and inflammation were evaluated at 48 h post-exposure to CEES. …


Swinging Lever Mechanism Of Myosin Directly Shown By Time-Resolved Cryo-Em, David P. Klebl, Sean N. Mcmillan, Cristina Risi, Eva Forgacs, Betty Virok, Jennifer L. Atherton, Sarah A. Harris, Michele Stofella, Donald A. Winkelmann, Frank Sobott, Vitold E. Galkin, Peter J. Knight, Stephen P. Muench, Charlotte A. Scarfi, Howard D. White Jan 2025

Swinging Lever Mechanism Of Myosin Directly Shown By Time-Resolved Cryo-Em, David P. Klebl, Sean N. Mcmillan, Cristina Risi, Eva Forgacs, Betty Virok, Jennifer L. Atherton, Sarah A. Harris, Michele Stofella, Donald A. Winkelmann, Frank Sobott, Vitold E. Galkin, Peter J. Knight, Stephen P. Muench, Charlotte A. Scarfi, Howard D. White

Department of Biomedical and Translational Sciences Faculty Publications

Myosins produce force and movement in cells through interactions with F-actin1. Generation of movement is thought to arise through actin-catalysed conversion of myosin from an ATP-generated primed (pre-powerstroke) state to a post-powerstroke state, accompanied by myosin lever swing2,3. However, the initial, primed actomyosin state has never been observed, and the mechanism by which actin catalyses myosin ATPase activity is unclear. Here, to address these issues, we performed time-resolved cryogenic electron microscopy (cryo-EM)4 of a myosin-5 mutant having slow hydrolysis product release5,6. Primed actomyosin was predominantly captured 10 ms after …


Balancing Regeneration And Resistance: Targeting Dclk1 To Mitigate Gastrointestinal Radiation Injury And Oncogenesis, Landon L. Moore, Jerry Jaboin, Milton L. Brown, Courtney W. Houchen Jan 2025

Balancing Regeneration And Resistance: Targeting Dclk1 To Mitigate Gastrointestinal Radiation Injury And Oncogenesis, Landon L. Moore, Jerry Jaboin, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

Ionizing radiation (IR) poses a dual challenge in medicine; while essential for cancer therapy, it inflicts collateral damage to normal tissues, particularly the gastrointestinal (GI) tract. High-dose IR triggers acute radiation syndrome (ARS), characterized by crypt stem cell depletion, mucosal barrier disruption, inflammation, and potential progression to fibrosis and secondary malignancy. Emerging evidence identifies the epithelial kinase doublecortin-like kinase 1 (DCLK1)—highly expressed in GI tuft cells and cancer stem-like cells—as a master regulator of post-IR responses. DCLK1 integrates DNA repair (via p53/ATM), and survival signaling (via NF-κB, TGF-β, and MAPK) to promote epithelial regeneration, yet these same mechanisms contribute to …


A Linear Presentation Of Cutaneous Rosai Dorfman Disease, Emily Sheetz, Ryan C. Saal, Molly K. Smith, Rachel Chikowski Byrd Jan 2025

A Linear Presentation Of Cutaneous Rosai Dorfman Disease, Emily Sheetz, Ryan C. Saal, Molly K. Smith, Rachel Chikowski Byrd

Department of Medicine Faculty Publications

[Case description] A 53-year-old female with type II diabetes and hypertension presented to the dermatology clinic with a 3-month history of an asymptomatic linear eruption along the right knee that extended distally along the shin. Initial biopsy showed an atypical lymphohistiocytic infiltrate (Fig 1), which was found to be polyclonal. At her 3-month follow up visit, the eruption demonstrated significant clinical progression with numerous indurated papules and papulonodules, some of which were tender, along the right knee and pretibial surface (Fig 2). No improvement was noted with topical triamcinolone prescribed at her initial visit.


The Pre-Polarization And Concentration Of Cells Near Micro-Electrodes Using Ac Electric Fields Enhances The Electrical Cell Lysis In A Sessile Drop, Kishor Kaphle, Dharmakeerthi Nawarathna Jan 2025

The Pre-Polarization And Concentration Of Cells Near Micro-Electrodes Using Ac Electric Fields Enhances The Electrical Cell Lysis In A Sessile Drop, Kishor Kaphle, Dharmakeerthi Nawarathna

Electrical & Computer Engineering Faculty Publications

Cell lysis is the starting step of many biomedical assays. Electric field-based cell lysis is widely used in many applications, including point-of-care (POC) applications, because it provides an easy one-step solution. Many electric field-based lysis methods utilize micro-electrodes to apply short electric pulses across cells. Unfortunately, these cell lysis devices produce relatively low cell lysis efficiency as electric fields do not reach a significant portion of cells in the sample. Additionally, the utility of syringe pumps for flow cells in and out of the microfluidics channel causes cell loss and low throughput cell lysis. To address these critical issues, we …


Development Of 2d Microfluidics Surface With Low-Frequency Electric Fields For Cell Separation Applications, Madushan Wickramasinghe, Dharmakeerthi Nawarathna Jan 2025

Development Of 2d Microfluidics Surface With Low-Frequency Electric Fields For Cell Separation Applications, Madushan Wickramasinghe, Dharmakeerthi Nawarathna

Electrical & Computer Engineering Faculty Publications

Cell separation techniques are widely used in many biomedical and clinical applications for the development of screening, diagnosis and therapeutic tests. Current 3D microfluidics-based cell separation methods have limited applications in part due to low throughput and technical complexity. To address these critical needs, we have developed a 2D microfluidics surface which is the miniaturized version of a 3D microfluids cell separation device. Using low-frequency electric fields (1–10 Vpp and 1 kHz–20 MHz), we have first studied dielectrophoresis, AC electro-osmosis and capillary flow within a sessile drop, and finally utilized the results to develop the 2D cell separation surface. Our …


The Role Of Tgf-Beta Superfamily Members In Immune Homeostasis And Disease, Natalie Eva Nieuwenhuizen, Ioannis Eleftherianos, Piotr Jan Kraj, Maria Semitekolou Jan 2025

The Role Of Tgf-Beta Superfamily Members In Immune Homeostasis And Disease, Natalie Eva Nieuwenhuizen, Ioannis Eleftherianos, Piotr Jan Kraj, Maria Semitekolou

Biological Sciences Faculty Publications

[Introduction] The Transforming Growth Factor beta (TGF-beta) superfamily, encompassing molecules such as TGFs, activins, Bone Morphogenetic Proteins (BMPs), Growth/Differentiation Factor (GDFs) and Nodals, represents the largest family of growth and differentiation factors, playing crucial roles in developmental and physiological processes across animal species (1). These molecules are integral to tissue homeostasis and cell fate determination. Among them, TGF-beta is particularly noted for its regulatory influence on immune responses and tissue fibrosis (2, 3). Recent research has expanded our understanding of the immune functions of other superfamily members, including activin A and BMPs (4). These molecules signal through receptor complexes composed …


Dengue Virus Modulates Critical Cell Cycle Regulatory Proteins In Human Megakaryocyte Cells, Swarnendu Basak, Shovan Dutta, Supreet Khanal, Girish Neelakanta, Hameeda Sultana Jan 2025

Dengue Virus Modulates Critical Cell Cycle Regulatory Proteins In Human Megakaryocyte Cells, Swarnendu Basak, Shovan Dutta, Supreet Khanal, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Suppression of human megakaryocytes by dengue virus (DENV) infection significantly reduces the platelet count that eventually leads to thrombocytopenia, severe dengue and death. To understand DENV interactions with megakaryocytes, we investigated the cell cycle in leukemic human megakaryocytic in vitro cell line (MEG-01 cells). Megakaryocytes are known for complex endomitotic cell cycle leading to their polyploidy state. Our study shows that DENV uses these polyploid cells for its replication. Understanding the modulation of DENV-mediated cell cycle regulation in megakaryocytes is therefore highly important. We show that DENV2 (serotype 2) infection significantly modulates cell cycle signaling. Our protein profile microarray data …


Enhancing Bone Regeneration Using Kaempferol As An Osteoprotective Compound: Signaling Mechanisms, Delivery Strategies, And Potential Applications, Mojdeh Salehi Namini, Sanam Mohandesnezhad, Sadaf Mohandesnezhad, Vahid Mansouri, Lobat Tayebi, Nima Beheshtizadeh Jan 2025

Enhancing Bone Regeneration Using Kaempferol As An Osteoprotective Compound: Signaling Mechanisms, Delivery Strategies, And Potential Applications, Mojdeh Salehi Namini, Sanam Mohandesnezhad, Sadaf Mohandesnezhad, Vahid Mansouri, Lobat Tayebi, Nima Beheshtizadeh

Electrical & Computer Engineering Faculty Publications

Various plants, including fruits, vegetables, and spices, contain kaempferol, a bioflavonoid compound with diverse medicinal effects, such as antioxidant, antibacterial, and anti-inflammatory characteristics. Furthermore, this compound exhibits multiple health-promoting properties, including osteoprotection and osteogenesis, primarily by modulating various cell-signaling pathways. This review aims to illustrate the medical advantages of kaempferol and its role in regulating bone metabolism through cell signaling mechanisms. Numerous studies have demonstrated the bone-protective properties of kaempferol and its encapsulated form. Further research is needed to clarify the optimal dosages, toxicity, safety, and other potential mechanisms of action. This review demonstrates that several signaling pathways, including nuclear …


Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu Jan 2025

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …