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894 results on '"Maric, Dragan"'

1. TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression

Author

Garcia-Montojo, Marta, Fathi, Saeed, Rastegar, Cyrus, Simula, Elena Rita, Doucet-O’Hare, Tara, Cheng, Y. H. Hank, Abrams, Rachel P. M., Pasternack, Nicholas, Malik, Nasir, Bachani, Muzna, Disanza, Brianna, Maric, Dragan, Lee, Myoung-Hwa, Wang, Herui, Santamaria, Ulisses, Li, Wenxue, Sampson, Kevon, Lorenzo, Juan Ramiro, Sanchez, Ignacio E., Mezghrani, Alexandre, Li, Yan, Sechi, Leonardo Antonio, Pineda, Sebastian, Heiman, Myriam, Kellis, Manolis, Steiner, Joseph, and Nath, Avindra

Published
2024
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2. Venous-plexus-associated lymphoid hubs support meningeal humoral immunity

Author

Fitzpatrick, Zachary, Ghabdan Zanluqui, Nagela, Rosenblum, Jared S., Tuong, Zewen Kelvin, Lee, Colin Y. C., Chandrashekhar, Vikram, Negro-Demontel, Maria Luciana, Stewart, Andrew P., Posner, David A., Buckley, Monica, Allinson, Kieren S. J., Mastorakos, Panagiotis, Chittiboina, Prashant, Maric, Dragan, Donahue, Danielle, Helmy, Adel, Tajsic, Tamara, Ferdinand, John R., Portet, Anais, Peñalver, Ana, Gillman, Eleanor, Zhuang, Zhengping, Clatworthy, Menna R., and McGavern, Dorian B.

Published
2024
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4. Multiplexed Immunofluorescence Brain Image Analysis Using Self-Supervised Dual-Loss Adaptive Masked Autoencoder

Author

Ly, Son T., Lin, Bai, Vo, Hung Q., Maric, Dragan, Roysam, Badri, and Nguyen, Hien V.

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Reliable large-scale cell detection and segmentation is the fundamental first step to understanding biological processes in the brain. The ability to phenotype cells at scale can accelerate preclinical drug evaluation and system-level brain histology studies. The impressive advances in deep learning offer a practical solution to cell image detection and segmentation. Unfortunately, categorizing cells and delineating their boundaries for training deep networks is an expensive process that requires skilled biologists. This paper presents a novel self-supervised Dual-Loss Adaptive Masked Autoencoder (DAMA) for learning rich features from multiplexed immunofluorescence brain images. DAMA's objective function minimizes the conditional entropy in pixel-level reconstruction and feature-level regression. Unlike existing self-supervised learning methods based on a random image masking strategy, DAMA employs a novel adaptive mask sampling strategy to maximize mutual information and effectively learn brain cell data. To the best of our knowledge, this is the first effort to develop a self-supervised learning method for multiplexed immunofluorescence brain images. Our extensive experiments demonstrate that DAMA features enable superior cell detection, segmentation, and classification performance without requiring many annotations., Comment: Adding new results on multiplexed image data and data efficiency. Pytorch code: https://github.com/hula-ai/DAMA

Published
2022

13. A cellular taxonomy of the adult human spinal cord

Author

Yadav, Archana, Matson, Kaya J.E., Li, Li, Hua, Isabelle, Petrescu, Joana, Kang, Kristy, Alkaslasi, Mor R., Lee, Dylan I., Hasan, Saadia, Galuta, Ahmad, Dedek, Annemarie, Ameri, Sara, Parnell, Jessica, Alshardan, Mohammad M., Qumqumji, Feras Abbas, Alhamad, Saud M., Wang, Alick Pingbei, Poulen, Gaetan, Lonjon, Nicolas, Vachiery-Lahaye, Florence, Gaur, Pallavi, Nalls, Mike A., Qi, Yue A., Maric, Dragan, Ward, Michael E., Hildebrand, Michael E., Mery, Pierre-Francois, Bourinet, Emmanuel, Bauchet, Luc, Tsai, Eve C., Phatnani, Hemali, Le Pichon, Claire E., Menon, Vilas, and Levine, Ariel J.

Published
2023
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15. Widespread subclinical cellular changes revealed across a neural-epithelial-vascular complex in choroideremia using adaptive optics

Author

Aguilera, Nancy, Liu, Tao, Bower, Andrew J., Li, Joanne, Abouassali, Sarah, Lu, Rongwen, Giannini, John, Pfau, Maximilian, Bender, Chelsea, Smelkinson, Margery G., Naik, Amelia, Guan, Bin, Schwartz, Owen, Volkov, Andrei, Dubra, Alfredo, Liu, Zhuolin, Hammer, Daniel X., Maric, Dragan, Fariss, Robert, Hufnagel, Robert B., Jeffrey, Brett G., Brooks, Brian P., Zein, Wadih M., Huryn, Laryssa A., and Tam, Johnny

Published
2022
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20. Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma

Author

Shah, Ashish H., Rivas, Sarah R., Doucet-O'Hare, Tara T., Govindarajan, Vaidya, DeMarino, Catherine, Wang, Tongguang, Ampie, Leonel, Zhang, Yong, Banasavadi-Siddegowda, Yeshavanth Kumar, Walbridge, Stuart, Maric, Dragan, Garcia-Montojo, Marta, Suter, Robert K., Lee, Myoung-Hwa, Zaghloul, Kareem A., Steiner, Joseph, Elkahloun, Abdel G., Chandar, Jay, Seetharam, Deepa, Desgraves, Jelisah, Li, Wenxue, Johnson, Kory, Ivan, Michael E., Komotar, Ricardo J., Gilbert, Mark R., Heiss, John D., and Nath, Avindra

Subjects
Stem cells -- Physiological aspects -- Health aspects, Endogenous retroviruses -- Physiological aspects -- Health aspects, Glioblastoma multiforme -- Development and progression, Health care industry
Abstract

Human endogenous retroviruses (HERVs) are ancestral viral relics that constitute nearly 8% of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be reactivated in certain cancers. Here, we report pathological expression of HML-2 in malignant gliomas in both cerebrospinal fluid and tumor tissue that was associated with a cancer stem cell phenotype and poor outcomes. Using single-cell RNA-Seq, we identified glioblastoma cellular populations with elevated HML-2 transcripts in neural progenitor-like cells (NPC-like) that drive cellular plasticity. Using CRISPR interference, we demonstrate that HML-2 critically maintained glioblastoma stemness and tumorigenesis in both glioblastoma neurospheres and intracranial orthotopic murine models. Additionally, we demonstrate that HML-2 critically regulated embryonic stem cell programs in NPC-derived astroglia and altered their 3D cellular morphology by activating the nuclear transcription factor OCT4, which binds to an HML-2-specific long- terminal repeat (LTR5Hs). Moreover, we discovered that some glioblastoma cells formed immature retroviral virions, and inhibiting HML-2 expression with antiretroviral drugs reduced reverse transcriptase activity in the extracellular compartment, tumor viability, and pluripotency. Our results suggest that HML-2 fundamentally contributes to the glioblastoma stem cell niche. Because persistence of glioblastoma stem cells is considered responsible for treatment resistance and recurrence, HML-2 may serve as a unique therapeutic target., Introduction Making up approximately 7%-8% of the human genome, human endogenous retroviruses (HERVs) are genomic remnants of exogenous retroviral germline infections (1-3). Because their function was largely elusive, HERVs were [...]

Published
2023
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24. Mapping The Nociceptive Secretome from Human Incisional Skin Samples Collected During Long Thoracic Surgery

Author

Li, Evelyn, primary, Sapio, Matthew R., additional, Domenichiello, Anthony F., additional, Manalo, Alison, additional, Goto, Taichi, additional, Maric, Dragan, additional, Williams, Tracy S., additional, Schrump, David S., additional, Davis, Jeremy L., additional, Hernandez, Jonathan M., additional, Blakely, Andrew M., additional, Iadarola, Michael J., additional, and Mannes, Andrew J., additional

Published
2024
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25. A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis

Author

Absinta, Martina, Maric, Dragan, Gharagozloo, Marjan, Garton, Thomas, Smith, Matthew D., Jin, Jing, and Fitzgerald, Kathryn C.

Subjects
Lymphocytes -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Multiple sclerosis (MS) lesions that do not resolve in the months after they form harbour ongoing demyelination and axon degeneration, and are identifiable in vivo by their paramagnetic rims on MRI scans.sup.1-3. Here, to define mechanisms underlying this disabling, progressive neurodegenerative state.sup.4-6 and foster development of new therapeutic agents, we used MRI-informed single-nucleus RNA sequencing to profile the edge of demyelinated white matter lesions at various stages of inflammation. We uncovered notable glial and immune cell diversity, especially at the chronically inflamed lesion edge. We define 'microglia inflamed in MS' (MIMS) and 'astrocytes inflamed in MS', glial phenotypes that demonstrate neurodegenerative programming. The MIMS transcriptional profile overlaps with that of microglia in other neurodegenerative diseases, suggesting that primary and secondary neurodegeneration share common mechanisms and could benefit from similar therapeutic approaches. We identify complement component 1q (C1q) as a critical mediator of MIMS activation, validated immunohistochemically in MS tissue, genetically by microglia-specific C1q ablation in mice with experimental autoimmune encephalomyelitis, and therapeutically by treating chronic experimental autoimmune encephalomyelitis with C1q blockade. C1q inhibition is a potential therapeutic avenue to address chronic white matter inflammation, which could be monitored by longitudinal assessment of its dynamic biomarker, paramagnetic rim lesions, using advanced MRI methods. Single-nucleus transcriptomics defines a diverse set of immune and glial cells at the chronically inflamed leading edge of demyelinated white matter lesions in patients with multiple sclerosis., Author(s): Martina Absinta [sup.1] [sup.2] [sup.3] , Dragan Maric [sup.4] , Marjan Gharagozloo [sup.1] , Thomas Garton [sup.1] , Matthew D. Smith [sup.1] , Jing Jin [sup.1] , Kathryn C. [...]

Published
2021
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30. Syntaxin1A overexpression and pain insensitivity in individuals with 7q11.23 duplication syndrome

Author

Iadarola, Michael J., primary, Sapio, Matthew R., additional, Loydpierson, Amelia J., additional, Mervis, Carolyn B., additional, Fehrenbacher, Jill C., additional, Vasko, Michael R., additional, Maric, Dragan, additional, Eisenberg, Daniel P., additional, Nash, Tiffany A., additional, Kippenhan, J. Shane, additional, Garvey, Madeline H., additional, Mannes, Andrew J., additional, Gregory, Michael D., additional, and Berman, Karen F., additional

Published
2024
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36. T cells target cerebrovasculature in children with cerebral malaria

Author

Riggle, Brittany A., Manglani, Monica, Maric, Dragan, Johnson, Kory R., Lee, Myoung-Hwa, Neto, Osorio Lopes Abath, Taylor, Terrie E., Seydel, Karl B., Nath, Avindra, Miller, Louis H., McGavern, Dorian B., and Pierce, Susan K.

Subjects
United States. National Institutes of Health, Thermo Fisher Scientific Inc., Artemisinin -- Youth market, Therapeutics -- Youth market, Immunohistochemistry, Comorbidity, Malaria, Scientific equipment industry -- Youth market, T cells, HIV, Diseases, Children, Health care industry
Abstract

BACKGROUND. Cerebral malaria (CM) accounts for nearly 400,000 deaths annually in African children. Current dogma suggests that CM results from infected RBC (iRBC) sequestration in the brain microvasculature and resulting sequelae. Therapies targeting these events have been unsuccessful; findings in experimental models suggest that [CD8.sup.+] T cells drive disease pathogenesis. However, these data have largely been ignored because corroborating evidence in humans is lacking. This work fills a critical gap in our understanding of CM pathogenesis that is impeding development of therapeutics. METHODS. Using multiplex immunohistochemistry, we characterized cerebrovascular immune cells in brain sections from 34 children who died from CM or other causes. Children were grouped by clinical diagnosis ([CM.sup.+] or CM), iRBC sequestration ([Seq.sup.hi], [Seq.sup.lo], [Seq.sup.0]) and HIV status ([HIV.sup.+] or [HIV.sup.-]). RESULTS. We identified effector [CD3.sup.+][CD8.sup.+] T cells engaged on the cerebrovasculature in 69% of [CM.sup.+] [HIV.sup.-] children. The number of intravascular [CD3.sup.+][CD8.sup.+] T cells was influenced by CM status ([CM.sup.+] > [CM.sup.-], P = 0.004) and sequestration level ([Seq.sup.hi] > [Seq.sup.lo], P = 0.010). HIV coinfection significantly increased T cell numbers (P = 0.017) and shifted cells from an intravascular (P = 0.004) to perivascular (P < 0.0001) distribution. CONCLUSION. Within the studied cohort, CM is associated with cerebrovascular engagement of [CD3.sup.+][CD8.sup.+] T cells, which is exacerbated by HIV coinfection. Thus, [CD3.sup.+][CD8.sup.+] T cells are highly promising targets for CM adjunctive therapy, opening new avenues for the treatment of this deadly disease. FUNDING. This research was supported by the Intramural Research Program of the National Institutes of Health., Introduction Plasmodium falciparum malaria is a potentially fatal infectious disease caused by mosquito-transmitted parasites. Last year P. falciparum infections caused over 219 million cases of malaria and 435,000 deaths, the [...]

Published
2020
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40. Laser Interstitial Thermal Therapy Induces Robust Local Immune Response for Newly Diagnosed Glioblastoma with Long-term Survival and Disease Control

Author

Chandar, Jay S., primary, Bhatia, Shovan, additional, Ingle, Shreya, additional, Mendez Valdez, Mynor J., additional, Maric, Dragan, additional, Seetharam, Deepa, additional, Desgraves, Jelisah F., additional, Govindarajan, Vaidya, additional, Daggubati, Lekhaj, additional, Merenzon, Martin, additional, Morell, Alexis, additional, Luther, Evan, additional, Saad, Ali G., additional, Komotar, Ricardo J., additional, Ivan, Michael E., additional, and Shah, Ashish H., additional

Published
2023
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43. CRH stimulation improves 18F-FDG-PET detection of pituitary adenomas in Cushing’s disease

Author

Boyle, Jacqueline, Patronas, Nicholas J., Smirniotopoulos, James, Herscovitch, Peter, Dieckman, William, Millo, Corina, Maric, Dragan, Chatain, Grégoire P., Hayes, Christina Piper, Benzo, Sarah, Scott, Gretchen, Edwards, Nancy, Ray Chaudhury, Abhik, Lodish, Maya B., Sharma, Susmeeta, Nieman, Lynnette K., Stratakis, Constantine A., Lonser, Russell R., and Chittiboina, Prashant

Published
2019
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48. Data from Proteostasis Modulation in Germline Missense von Hippel Lindau Disease

Author

Chittiboina, Prashant, primary, Mandal, Debjani, primary, Bugarini, Alejandro, primary, Asuzu, David T., primary, Mullaney, Dustin, primary, Mastorakos, Panagiotis, primary, Stoica, Stefan, primary, Alvarez, Reinier, primary, Scott, Gretchen, primary, Maric, Dragan, primary, Elkahloun, Abdel, primary, Zhuang, Zhengping, primary, Chew, Emily Y., primary, Yang, Chunzhang, primary, Linehan, Marston, primary, and Lonser, Russell R., primary

Published
2023
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50. Pain control through selective chemo-axotomy of centrally projecting [TRPV1.sup.+] sensory neurons

Author

Sapio, Matthew R., Neubert, John K., LaPaglia, Danielle M., Maric, Dragan, Keller, Jason M., Raithel, Stephen J., Rohrs, Eric L., Anderson, Ethan M., Butman, John A., Caudle, Robert M., Brown, Dorothy C., Heiss, John D., Mannes, Andrew J., and Iadarola, Michael J.

Subjects
Nociception -- Research, Medical research, Alkaloids -- Health aspects -- Physiological aspects, Pain management -- Research, Ion channels -- Physiological aspects -- Health aspects, Somatosensory system -- Research, Health care industry
Abstract

Agonists of the vanilloid receptor transient vanilloid potential 1 (TRPV1) are emerging as highly efficacious nonopioid analgesics in preclinical studies. These drugs selectively lesion [TRPV1.sup.+] primary sensory afferents, which are responsible for the transmission of many noxious stimulus modalities. Resiniferatoxin (RTX) is a very potent and selective TRPV1 agonist and is a promising candidate for treating many types of pain. Recent work establishing intrathecal application of RTX for the treatment of pain resulting from advanced cancer has demonstrated profound analgesia in client-owned dogs with osteosarcoma. The present study uses transcriptomics and histochemistry to examine the molecular mechanism of RTX action in rats, in clinical canine subjects, and in 1 human subject with advanced cancer treated for pain using intrathecal RTX. In all 3 species, we observe a strong analgesic action, yet this was accompanied by limited transcriptional alterations at the level of the dorsal root ganglion. Functional and neuroanatomical studies demonstrated that intrathecal RTX largely spares susceptible neuronal perikarya, which remain active peripherally but unable to transmit signals to the spinal cord. The results demonstrate that central chemo-axotomy of the [TRPV1.sup.+] afferents underlies RTX analgesia and refine the neurobiology underlying effective clinical use of TRPV1 agonists for pain control., Introduction Severe chronic pain remains a medically intractable problem with life-altering consequences. While most chronic pain is currently treated with any number of drugs, including opioids, NSAIDs, and calcium channel [...]

Published
2018
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