Article
Chemistry, Analytical
Diwakar M. Awate, Cicero C. Pola, Erica Shumaker, Carmen L. Gomes, Jaime J. Juarez
Summary: Despite the limitations of flow cytometers, a 3D-printed imaging platform (3DPIP) has been developed to accurately count particles and conduct fluorescence microscopy efficiently. The 3DPIP utilizes a custom particle counter code and machine vision-based algorithm to identify and count particles, showing comparable accuracy to commercial particle counters. Additionally, the platform can perform static experiments and flow-through experiments effectively, making it a promising tool for use in resource-limited clinical environments.
Article
Biochemical Research Methods
Ahmad Shirazi, Tayebeh Sahraeibelverdi, Miki Lee, Haijun Li, Joonyoung Yu, Sangeeta Jaiswal, Kenn R. Oldham, Thomas D. Wang
Summary: We demonstrate a side-view dual axes confocal endomicroscope that can be repetitively inserted in hollow organs of genetically engineered mice for in vivo real-time imaging in both horizontal and vertical planes. Near infrared (NIR) excitation at λex = 785 nm was used, and a monolithic 3-axis parametric resonance scan mirror fabricated using micro-electromechanical systems (MEMS) technology enabled post-objective scanning in the distal end of a 4.19 mm diameter instrument. Torsional and serpentine springs were designed to switch the mode of imaging between vertical and horizontal planes by tuning the actuation frequency. This system achieved real-time in-vivo images with a depth of 310 μm and lateral and axial resolution of 1.75 and 7.5 μm, respectively, in both horizontal and vertical planes, allowing identification of individual cells and discrete mucosal structures.
BIOMEDICAL OPTICS EXPRESS
(2023)
Article
Multidisciplinary Sciences
Estelle Carminita, Lydie Crescence, Nicolas Brouilly, Alexandre Altie, Laurence Panicot-Dubois, Christophe Dubois
Summary: The research indicates that neutrophils rather than NETs are involved in thrombus formation after laser-induced injury. Treatment with DNase-I leads to hydrolysis of ATP and ADP, generating adenosine and inhibiting thrombus formation in vivo.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Jina Ko, Kilean Lucas, Rainer Kohler, Elias A. Halabi, Martin Wilkovitsch, Jonathan C. T. Carlson, Ralph Weissleder
Summary: The ability to observe cells in live organisms is crucial for understanding their function in complex in vivo milieus. However, current methods have limited multiplexing capacity. In this study, a click chemistry-based strategy called scission-accelerated fluorophore exchange (SAFE) was developed for higher multiplexed in vivo imaging in mouse models. The method allows specific cell staining, complete un-staining, and non-toxic in vivo click chemistries at lower concentrations. It also enables cyclic imaging and has demonstrated potential utility in imaging immune cells with 12 colors.
Article
Chemistry, Multidisciplinary
Kazunori Igarashi, Horacio Cabral, Taehun Hong, Yasutaka Anraku, Fotios Mpekris, Triantafyllos Stylianopoulos, Thahomina Khan, Akira Matsumoto, Kazunori Kataoka, Yu Matsumoto, Tatsuya Yamasoba
Summary: Recent research has highlighted the potential of dynamic bursting in tumor vasculature as a novel route for drug delivery, allowing for the transportation of sub-100 nm nanoparticles into tumors and possibly affecting the access of other blood-borne particles. Mathematical modeling and experimental comparisons have revealed the characteristics and sizes of burst vents in tumor vasculature, as well as different types of therapeutic drugs and cells that can utilize this phenomenon for transportation.
Article
Multidisciplinary Sciences
Ran Brosh, Jon M. Laurent, Raquel Ordonez, Emily Huang, Megan S. Hogan, Angela M. Hitchcock, Leslie A. Mitchell, Sudarshan Pinglay, John A. Cadley, Raven D. Luther, David M. Truong, Jef D. Boeke, Matthew T. Maurano
Summary: Big-IN is a versatile platform for targeted integration of large DNAs into mammalian cells, enabling functional analysis and verification of engineered stem cells. This approach allows for the integration of constructs into cells, providing the potential for systematic analysis of disease-related genomic loci.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Endocrinology & Metabolism
Shiuhwei Chen, ZhiJiang Huang, Harrison Kidd, Min Kim, Eul Hyun Suh, Shangkui Xie, Ebrahim H. Ghazvini Zadeh, Yan Xu, A. Dean Sherry, Philipp E. Scherer, Wen-hong Li
Summary: Appropriate insulin secretion is crucial for maintaining euglycemia and understanding the dynamics of insulin secretion at the cellular level in intact pancreas of living animals remains challenging. Through ZIMIR imaging, insulin/Zn2+ release of individual islet beta-cells can be tracked with high spatiotemporal resolution, revealing synchronized rhythmic secretion activity. Additionally, the use of chemogenetic approach and fluorescent granule zinc indicator show promise for selective and efficient islet cell labeling in living animals.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Endocrinology & Metabolism
Michael P. Dybala, Manami Hara
Summary: The pancreas is composed of two separate systems - the endocrine and exocrine pancreas. Treatment of diseases affecting either system may impact the overall pancreatic function, leading to different disciplines of medical professionals providing treatment. A new model suggests that islet blood flow is integrated with the surrounding exocrine capillary network, potentially offering new hypotheses for pancreatic diseases and their regulation of hormones and functions.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Immunology
Flavian Thelen, Stefanie Wissmann, Nora Ruef, Jens Stein
Summary: Naive T cells constantly circulate through secondary lymphoid organs in search of antigens to maintain cell homeostasis. Tec kinases and Tiam1 play roles in CCR7-mediated T cell migration and homeostasis, although the specific mechanisms are not fully understood.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Marie Carriere, Paulo Henrique M. Buzzetti, Karine Gorgy, Muhammad Mumtaz, Christophe Travelet, Redouane Borsali, Serge Cosnier
Summary: A series of new glyconanoparticles were successfully obtained by self-assembly and post-functionalization, showcasing spherical morphology and nanometric size. These particles exhibit classical electroactivity and the amount of immobilized redox compound is proportional to the percentage of polystyrene-block-beta-cyclodextrin in the composition. Modulation of surface density of beta-cyclodextrin on the nanoparticles shell may lead to the preparation of different electroactive particles and those modified by biotinylated proteins.
Article
Cell Biology
Andreas Margraf, Markus Sperandio
Summary: This practical guide introduces a mouse model for real-time observation of the fetal yolk-sac and corporal microvasculature. By anesthetizing pregnant mice, opening the abdominal cavity to expose the uterine horn, using microinjection methods to deliver substances directly to the fetal circulation, and administering substances crossing the placenta via the maternal circulation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemical Research Methods
Caleb A. Dawson, Scott N. Mueller, Geoffrey J. Lindeman, Anne C. Rios, Jane E. Visvader
Summary: The protocol presented offers a method for high-quality, six-color 3D intravital imaging of mouse mammary tissue, maintaining tissue access through skin-flap surgery and chamber preparation for high-resolution imaging.
Review
Immunology
Sophia M. Vrba, Heather D. Hickman
Summary: In the past decade, global public health crises caused by emerging viral infections have led to a greater understanding of successful antiviral immune responses, with advancements in microscopy allowing for real-time visualization of viral infection. Intravital imaging has provided unique insights into the relationships between immune effectors and virus-infected cells, leading to significant discoveries about virus/host interactions and antiviral effector cell biology.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Victor A. Naumenko, Daniil A. Vishnevskiy, Aleksei A. Stepanenko, Anastasiia O. Sosnovtseva, Anastasiia A. Chernysheva, Tatiana O. Abakumova, Marat P. Valikhov, Anastasiia Lipatova, Maxim A. Abakumov, Vladimir P. Chekhonin
Summary: Hepatotoxicity is a problem in adenovirus cancer therapy, caused by Kupffer cell death and hepatocyte transduction. The interaction between adenovirus and liver cells is not well understood. This study used intravital microscopy to track the infection and immune response in mouse livers after adenovirus injection, and found that Ad5-RGD and Ad5/3 caused macrophage deformation and virus release, but neutrophils and CD8+ T cells did not affect the rate or dynamics of liver infection. Ad5-RGD failed to complete the replicative cycle in hepatocytes, but enhanced liver transduction during hepatic regeneration.
Review
Biochemistry & Molecular Biology
Alberto Bartolome
Summary: This article reviews different models to study the genetic basis of beta cell dysfunction, focusing on the recent advances made possible by stem cell applications in the field of diabetes research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Marilyn Arosemena, Farah A. Meah, Kieren J. Mather, Sarah A. Tersey, Raghavendra G. Mirmira
Summary: The biomarkers of beta-cell death in diabetes indicate that beta-cell death may occur in individuals with obesity and T2D, but more refined study designs are needed to better align sampling with disease progression events.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Abhishek Kulkarni, Jerry L. Nadler, Raghavendra G. Mirmira, Isabel Casimiro
Summary: 12-LOX is a key lipid metabolizing enzyme that plays an important role in inflammatory diseases. Increased activity of 12-LOX can lead to tissue damage and enhanced migration of immune cells, while inhibition of this enzyme can protect against disease development and progression in animal models.
Review
Pharmacology & Pharmacy
Soumyadeep Sarkar, John T. Melchior, Hayden R. Henry, Farooq Syed, Raghavendra G. Mirmira, Ernesto S. Nakayasu, Thomas O. Metz
Summary: This paper discusses the potential role of GDF15 in preventing insulitis and protecting pancreatic beta cells against cellular stress. Although GDF15 shows promise as a potential intervention, further development is needed, and challenges such as anorexia and short half-life need to be addressed.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Biochemistry & Molecular Biology
Abhishek Kulkarni, Sara Ibrahim, Isra Haider, Amina Basha, Emma Montgomery, Ebru Ermis, Raghavendra G. Mirmira, Ryan M. Anderson
Summary: In this study, a novel 2-hit zebrafish model was established to replicate aspects of NAFLD pathogenesis, providing a new tool for studying the early pathological mechanisms of NAFLD. The zebrafish model also demonstrated the feasibility of in vivo screening of new pharmacological interventions.
Meeting Abstract
Endocrinology & Metabolism
Fei Huang, Abhishek Kulkarni, Farooq Syed, David J. Maloney, Sarah A. Tersey, Raghavendra G. Mirmira
Review
Biochemistry & Molecular Biology
Abhishek Kulkarni, Cara M. Anderson, Raghavendra G. Mirmira, Sarah A. Tersey
Summary: This review summarizes the existing research on polyamine-hypusine metabolism in the context of beta-cell function and diabetes pathogenesis.
Article
Cell Biology
Annie R. Pineros, Abhishek Kulkarni, Hongyu Gao, Kara S. Orr, Lindsey Glenn, Fei Huang, Yunlong Liu, Maureen Gannon, Farooq Syed, Wenting Wu, Cara M. Anderson, Carmella Evans-Molina, Marcia McDuffie, Jerry L. Nadler, Margaret A. Morris, Raghavendra G. Mirmira, Sarah A. Tersey
Summary: This study suggests that inflammatory signaling in beta cells promotes autoimmunity during the progression of type 1 diabetes. By deleting a specific proinflammatory gene in mice, the researchers found that the preservation of beta cell mass and reduction in infiltrating T cell populations protected against spontaneous autoimmune diabetes.
Review
Endocrinology & Metabolism
Rebecca S. Aguirre, Abhishek Kulkarni, Matthew W. Becker, Xiaoyong Lei, Soumyadeep Sarkar, Sasanka Ramanadham, Edward A. Phelps, Ernesto S. Nakayasu, Emily K. Sims, Raghavendra G. Mirmira
Summary: This review examines the impact of extracellular vesicles (EVs) released by pancreatic islet beta cells on the development of type 1 diabetes (T1D). The formation and cargo of EVs play important roles in the pathogenesis of T1D and have the potential to serve as biomarkers or therapeutic candidates.
MOLECULAR METABOLISM
(2022)
Review
Biochemistry & Molecular Biology
Amina Basha, Sarah C. C. May, Ryan M. M. Anderson, Niharika Samala, Raghavendra G. G. Mirmira
Summary: Nonalcoholic fatty liver disease (NAFLD) is a common liver disease caused by fat accumulation in the liver without excess alcohol use or other liver disease causes. Its complications include cirrhosis, liver failure, hepatocellular carcinoma, and death. The pathophysiology of NAFLD, including insulin resistance and inflammation, remains poorly understood. Animal models have played a crucial role in defining these mechanisms and developing therapies for NAFLD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Titli Nargis, Annie R. Pineros, Sarah C. May, Sarah A. Tersey, Raghavendra G. Mirmira
Summary: This protocol presents a method to isolate and analyze immune cells from mouse pancreatic lymph nodes and whole pancreas, which can be used to investigate critical immune cell subsets in autoimmune diabetes and can be adapted for studying resident immune cells from other tissues.
Article
Oncology
Shima Nakanishi, Jiannong Li, Anders E. Berglund, Youngchul Kim, Yonghong Zhang, Ling Zhang, Chunying Yang, Jinming Song, Raghavendra G. Mirmira, John L. Cleveland
Summary: The MYC oncoprotein activates the poly-amine-hypusine circuit, which modifi es the eukaryotic translation factor eIF5A. Loss of eIF5A hypusination abolishes malignant transformation of MYC-overexpressing B cells. This circuit controls MYC's proliferative response and is activated in multiple malignancies. The hypusine circuit may serve as a therapeutic target for several human tumor types.
BLOOD CANCER DISCOVERY
(2023)
Review
Pharmacology & Pharmacy
Ivo Diaz Ludovico, Soumyadeep Sarkar, Emily Elliott, Suvi M. Virtanen, Iris Erlund, Sasanka Ramanadham, Raghavendra G. Mirmira, Thomas O. Metz, Ernesto S. Nakayasu
Summary: This article provides an overview of the role of fatty acids in type 1 diabetes and their potential as therapeutic targets. It discusses the regulation of lipotoxicity and inflammatory response, the impact of diet on fatty acid availability and disease development, and avenues for further exploration.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Biochemistry & Molecular Biology
Matthew Martin, Aishat Motolani, Hyeong-Geug Kim, Amy M. Collins, Faranak Alipourgivi, Jiamin Jin, Han Wei, Barry A. Wood, Yao-Ying Ma, X. Charlie Dong, Raghavendra G. Mirmira, Tao Lu
Summary: Dysregulation of metabolic functions in the liver affects the development of diabetes and metabolic disorders. The study identifies lysine demethylase 2A (KDM2A) as a negative regulator of nuclear factor (NF)-kappa B in the liver, with a crucial role in liver function. Through a liver-specific Kdm2a knockout mouse model, it is shown that KDM2A deficiency leads to liver dysfunction and increased inflammation.
Article
Biology
A. H. F. Vale, D. C. Nascimento, A. R. Pineros, R. G. Ferreira, J. D. Santos, D. C. Aragon, F. Q. Cunha, F. S. Ramalho, J. C. Alves-Filho, A. P. C. P. Carlotti
Summary: This study aimed to evaluate whether administration of riboflavin reduces inflammation, oxidative stress, organ dysfunction, and mortality in septic animals. The results showed that riboflavin did not reduce inflammation, oxidative stress, organ dysfunction, or mortality compared with placebo in mice undergoing sepsis induced by cecal ligation and puncture (CLP).
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
(2022)