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  1. Article: Utilizing multimodal mass spectrometry imaging for profiling immune cell composition and N-glycosylation across colorectal carcinoma disease progression.

    Young, Lyndsay E A / Nietert, Paul J / Stubler, Rachel / Kittrell, Caroline G / Grimsley, Grace / Lewin, David N / Mehta, Anand S / Hajar, Chadi / Wang, Katherine / O'Quinn, Elizabeth C / Angel, Peggi M / Wallace, Kristin / Drake, Richard R

    Frontiers in pharmacology

    2024  Volume 14, Page(s) 1337319

    Abstract: Colorectal cancer (CRC) stands as a leading cause of death worldwide, often arising from specific genetic mutations, progressing from pre-cancerous adenomas to adenocarcinomas. Early detection through regular screening can result in a 90% 5-year survival ...

    Abstract Colorectal cancer (CRC) stands as a leading cause of death worldwide, often arising from specific genetic mutations, progressing from pre-cancerous adenomas to adenocarcinomas. Early detection through regular screening can result in a 90% 5-year survival rate for patients. However, unfortunately, only a fraction of CRC cases are identified at pre-invasive stages, allowing progression to occur silently over 10-15 years. The intricate interplay between the immune system and tumor cells within the tumor microenvironment plays a pivotal role in the progression of CRC. Immune cell clusters can either inhibit or facilitate tumor initiation, growth, and metastasis. To gain a better understanding of this relationship, we conducted N-glycomic profiling using matrix-assisted laser desorption-ionization mass spectrometry imaging (MALDI-MSI). We detected nearly 100 N-glycan species across all samples, revealing a shift in N-glycome profiles from normal to cancerous tissues, marked by a decrease in high mannose N-glycans. Further analysis of precancerous to invasive carcinomas showed an increase in pauci-mannose biantennary, and tetraantennary N-glycans with disease progression. Moreover, a distinct stratification in the N-glycome profile was observed between non-mucinous and mucinous CRC tissues, driven by pauci-mannose, high mannose, and bisecting N-glycans. Notably, we identified immune clusters of CD20
    Language English
    Publishing date 2024-01-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2023.1337319
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Emerging roles of N-linked glycosylation in brain physiology and disorders.

    Conroy, Lindsey R / Hawkinson, Tara R / Young, Lyndsay E A / Gentry, Matthew S / Sun, Ramon C

    Trends in endocrinology and metabolism: TEM

    2021  Volume 32, Issue 12, Page(s) 980–993

    Abstract: N-linked glycosylation is a complex, co- and post-translational series of events that connects metabolism to signaling in almost all cells. Metabolic assembly of N-linked glycans spans multiple cellular compartments, and early N-linked glycan ... ...

    Abstract N-linked glycosylation is a complex, co- and post-translational series of events that connects metabolism to signaling in almost all cells. Metabolic assembly of N-linked glycans spans multiple cellular compartments, and early N-linked glycan biosynthesis is a central mediator of protein folding and the unfolded protein response (UPR). In the brain, N-linked glycosylated proteins participate in a myriad of processes, from electrical gradients to neurotransmission. However, it is less clear how perturbations in N-linked glycosylation impact and even potentially drive aspects of neurological disorders. In this review, we discuss our current understanding of the metabolic origins of N-linked glycans in the brain, their role in modulating neuronal function, and how aberrant N-linked glycosylation can drive neurological disorders.
    MeSH term(s) Brain/metabolism ; Glycosylation ; Humans ; Polysaccharides/metabolism ; Protein Processing, Post-Translational ; Signal Transduction
    Chemical Substances Polysaccharides
    Language English
    Publishing date 2021-10-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1042384-9
    ISSN 1879-3061 ; 1043-2760
    ISSN (online) 1879-3061
    ISSN 1043-2760
    DOI 10.1016/j.tem.2021.09.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: RIT1 regulation of CNS lipids RIT1 deficiency Alters cerebral lipid metabolism and reduces white matter tract oligodendrocytes and conduction velocities.

    Wu, Lei / Wang, Fang / Moncman, Carole L / Pandey, Mritunjay / Clarke, Harrison A / Frazier, Hilaree N / Young, Lyndsay E A / Gentry, Matthew S / Cai, Weikang / Thibault, Olivier / Sun, Ramon C / Andres, Douglas A

    Heliyon

    2023  Volume 9, Issue 10, Page(s) e20384

    Abstract: Oligodendrocytes (OLs) generate lipid-rich myelin membranes that wrap axons to enable efficient transmission of electrical impulses. Using ... ...

    Abstract Oligodendrocytes (OLs) generate lipid-rich myelin membranes that wrap axons to enable efficient transmission of electrical impulses. Using a
    Language English
    Publishing date 2023-09-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2023.e20384
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: TgLaforin, a glucan phosphatase, reveals the dynamic role of storage polysaccharides in

    Murphy, Robert D / Troublefield, Cortni A / Miracle, Joy S / Young, Lyndsay E A / Brizzee, Corey O / Dhara, Animesh / Sun, Ramon C / Vander Kooi, Craig W / Gentry, Matthew S / Sinai, Anthony P

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The asexual stages ... ...

    Abstract The asexual stages of
    Language English
    Publishing date 2023-09-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.29.560185
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cervical spinal cord injury leads to injury and altered metabolism in the lungs.

    Huffman, Emily E / Dong, Brittany E / Clarke, Harrison A / Young, Lyndsay E A / Gentry, Matthew S / Allison, Derek B / Sun, Ramon C / Waters, Christopher M / Alilain, Warren J

    Brain communications

    2023  Volume 5, Issue 2, Page(s) fcad091

    Abstract: High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality ... ...

    Abstract High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury
    Language English
    Publishing date 2023-03-28
    Publishing country England
    Document type Journal Article
    ISSN 2632-1297
    ISSN (online) 2632-1297
    DOI 10.1093/braincomms/fcad091
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Spatial profiling of gangliosides in mouse brain by mass spectrometry imaging.

    Andres, Douglas A / Young, Lyndsay E A / Gentry, Matthew S / Sun, Ramon C

    Journal of lipid research

    2020  Volume 61, Issue 12, Page(s) 1537

    MeSH term(s) Animals ; Brain/metabolism ; Gangliosides/metabolism ; Mass Spectrometry ; Mice ; Molecular Imaging
    Chemical Substances Gangliosides
    Language English
    Publishing date 2020-06-01
    Publishing country United States
    Document type Editorial
    ZDB-ID 80154-9
    ISSN 1539-7262 ; 0022-2275
    ISSN (online) 1539-7262
    ISSN 0022-2275
    DOI 10.1194/jlr.ILR120000870
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Inhibition of mitochondrial fission activates glycogen synthesis to support cell survival in colon cancer.

    Hasani, Sumati / Young, Lyndsay E A / Van Nort, Warren / Banerjee, Moumita / Rivas, Dylan R / Kim, Jinhwan / Xiong, Xiaopeng / Sun, Ramon C / Gentry, Matthew S / Sesaki, Hiromi / Gao, Tianyan

    Cell death & disease

    2023  Volume 14, Issue 10, Page(s) 664

    Abstract: Metabolic reprogramming has been recognized as one of the major mechanisms that fuel tumor initiation and progression. Our previous studies demonstrate that activation of Drp1 promotes fatty acid oxidation and downstream Wnt signaling. Here we ... ...

    Abstract Metabolic reprogramming has been recognized as one of the major mechanisms that fuel tumor initiation and progression. Our previous studies demonstrate that activation of Drp1 promotes fatty acid oxidation and downstream Wnt signaling. Here we investigate the role of Drp1 in regulating glycogen metabolism in colon cancer. Knockdown of Drp1 decreases mitochondrial respiration without increasing glycolysis. Analysis of cellular metabolites reveals that the levels of glucose-6-phosphate, a precursor for glycogenesis, are significantly elevated whereas pyruvate and other TCA cycle metabolites remain unchanged in Drp1 knockdown cells. Additionally, silencing Drp1 activates AMPK to stimulate the expression glycogen synthase 1 (GYS1) mRNA and promote glycogen storage. Using 3D organoids from Apc
    MeSH term(s) Humans ; Glycogenolysis ; Cell Survival ; Mitochondrial Dynamics ; Cell Transformation, Neoplastic ; Glycogen/metabolism ; Colonic Neoplasms/genetics ; Dynamins/metabolism
    Chemical Substances Glycogen (9005-79-2) ; Dynamins (EC 3.6.5.5)
    Language English
    Publishing date 2023-10-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-023-06202-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Genetic analysis of KillerRed in C. elegans identifies a shared role of calcium genes in ROS-mediated neurodegeneration.

    Young, Lyndsay E A / Shoben, Chelsea / Ricci, Kyra / Williams, Daniel C

    Journal of neurogenetics

    2018  Volume 33, Issue 1, Page(s) 1–9

    Abstract: In C. elegans, neurodegeneration induced by excitotoxicity or aggregation of misfolded proteins is dependent on genes involved in calcium release from the endoplasmic reticulum. Reactive oxygen species (ROS) can also induce neurodegeneration, but the ... ...

    Abstract In C. elegans, neurodegeneration induced by excitotoxicity or aggregation of misfolded proteins is dependent on genes involved in calcium release from the endoplasmic reticulum. Reactive oxygen species (ROS) can also induce neurodegeneration, but the relationship between ROS-mediated neurodegeneration and calcium has not been established. We activated KillerRed in the GABA neurons of C. elegans to produce ROS that leads to functional loss and structural degeneration of these neurons and demonstrated that the severity of neurodegeneration was dependent on extent of KillerRed activation. To genetically examine the role of calcium in ROS-mediated neurodegeneration, we measured functional neurodegeneration in itr-1 (inositol trisphosphate receptor), crt-1 (caltreticulin), and unc-68 (ryanodine receptor) mutants. Similar to other neurotoxic conditions, neurodegeneration triggered by KillerRed was reduced in itr-1 and crt-1 mutants. Somewhat unexpectedly, genetic or pharmacological disruption of unc-68 had a minimal effect on neurodegeneration. Our results indicate ROS-mediated neurodegeneration occurs through a conserved calcium regulated mechanism and suggest that components of the degeneration process have different sensitivities to ROS.
    MeSH term(s) Animals ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/genetics ; Calcium/metabolism ; Calreticulin/genetics ; GABAergic Neurons/metabolism ; GABAergic Neurons/pathology ; Green Fluorescent Proteins/toxicity ; Inositol 1,4,5-Trisphosphate Receptors/genetics ; Nerve Degeneration/chemically induced ; Nerve Degeneration/genetics ; Nerve Degeneration/metabolism ; Reactive Oxygen Species/metabolism ; Ryanodine Receptor Calcium Release Channel/genetics
    Chemical Substances CRT-1 protein, C elegans ; Caenorhabditis elegans Proteins ; Calreticulin ; Inositol 1,4,5-Trisphosphate Receptors ; Reactive Oxygen Species ; Ryanodine Receptor Calcium Release Channel ; Unc-68 protein, C elegans ; killer red protein, Anthomedusae ; Green Fluorescent Proteins (147336-22-9) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2018-11-29
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 605543-6
    ISSN 1563-5260 ; 0167-7063
    ISSN (online) 1563-5260
    ISSN 0167-7063
    DOI 10.1080/01677063.2018.1531857
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Enhancing lifespan of budding yeast by pharmacological lowering of amino acid pools.

    Hepowit, Nathaniel L / Macedo, Jessica K A / Young, Lyndsay E A / Liu, Ke / Sun, Ramon C / MacGurn, Jason A / Dickson, Robert C

    Aging

    2021  Volume 13, Issue 6, Page(s) 7846–7871

    Abstract: The increasing prevalence of age-related diseases and resulting healthcare insecurity and emotional burden require novel treatment approaches. Several promising strategies seek to limit nutrients and promote healthy aging. Unfortunately, the human desire ...

    Abstract The increasing prevalence of age-related diseases and resulting healthcare insecurity and emotional burden require novel treatment approaches. Several promising strategies seek to limit nutrients and promote healthy aging. Unfortunately, the human desire to consume food means this strategy is not practical for most people but pharmacological approaches might be a viable alternative. We previously showed that myriocin, which impairs sphingolipid synthesis, increases lifespan in
    MeSH term(s) Amino Acids/metabolism ; Dose-Response Relationship, Drug ; Longevity/drug effects ; Proteins/metabolism ; Saccharomyces cerevisiae/drug effects ; Saccharomyces cerevisiae/physiology ; Signal Transduction/drug effects ; Sphingosine/analogs & derivatives ; Sphingosine/pharmacology
    Chemical Substances Amino Acids ; Proteins ; major urinary proteins ; phytosphingosine (GIN46U9Q2Q) ; Sphingosine (NGZ37HRE42)
    Language English
    Publishing date 2021-03-21
    Publishing country United States
    Document type Journal Article
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.202849
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: In Situ

    Conroy, Lindsey R / Stanback, Alexandra E / Young, Lyndsay E A / Clarke, Harrison A / Austin, Grant L / Liu, Jinze / Allison, Derek B / Sun, Ramon C

    Molecular cancer research : MCR

    2021  Volume 19, Issue 10, Page(s) 1727–1738

    Abstract: Prostate cancer is the most common cancer in men worldwide. Despite its prevalence, there is a critical knowledge gap in understanding factors driving disparities in survival among different cohorts of patients with prostate cancer. Identifying molecular ...

    Abstract Prostate cancer is the most common cancer in men worldwide. Despite its prevalence, there is a critical knowledge gap in understanding factors driving disparities in survival among different cohorts of patients with prostate cancer. Identifying molecular features separating disparate populations is an important first step in prostate cancer research that could lead to fundamental hypotheses in prostate biology, predictive biomarker discovery, and personalized therapy. N-linked glycosylation is a cotranslational event during protein folding that modulates a myriad of cellular processes. Recently, aberrant N-linked glycosylation has been reported in prostate cancers. However, the full clinical implications of dysregulated glycosylation in prostate cancer has yet to be explored. Herein, we performed direct on-tissue analysis of N-linked glycans using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) from tissue microarrays of over 100 patient tumors with over 10 years of follow-up metadata. We successfully identified a panel of N-glycans that are unique between benign and prostate tumor tissue. Specifically, high-mannose as well as tri-and tetra-antennary N-glycans were more abundant in tumor tissue and increase proportionally with tumor grade. Further, we expanded our analyses to examine the N-glycan profiles of Black and Appalachian patients and have identified unique glycan signatures that correlate with recurrence in each population. Our study highlights the potential applications of MALDI-MSI for digital pathology and biomarker discovery for prostate cancer. IMPLICATIONS: MALDI-MSI identifies N-glycan perturbations in prostate tumors compared with benign tissue. This method can be utilized to predict prostate cancer recurrence and study prostate cancer disparities.
    MeSH term(s) Biomarkers, Tumor/metabolism ; Glycosylation ; Humans ; Male ; Neoplasm Recurrence, Local/metabolism ; Neoplasm Recurrence, Local/pathology ; Polysaccharides/metabolism ; Prostate/pathology ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; Tissue Fixation/methods
    Chemical Substances Biomarkers, Tumor ; Polysaccharides
    Language English
    Publishing date 2021-06-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2098788-2
    ISSN 1557-3125 ; 1541-7786
    ISSN (online) 1557-3125
    ISSN 1541-7786
    DOI 10.1158/1541-7786.MCR-20-0967
    Database MEDical Literature Analysis and Retrieval System OnLINE

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