Current Search: Department of Biomedical Science (x)
View All Items
Pages
- Title
- Effect of amyloid beta on nutrient uptake and ATP in the brain cells.
- Creator
- To, William, Tao, Rui, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Unintentional weight loss in older adults often precedes Alzheimer’s disease (AD). Positron emission tomography (PET) scan reveals that AD patients exhibit reduced uptake of fluorodeoxyglucose into brain cells, defined as ‘hypometabolism’. However, cellular mechanisms underlying weight loss and hypometabolism have not received much attention. The primary goal of the study was to test the hypothesis that cells become starved in confrontation with amyloid beta proteins (Aβ), which are...
Show moreUnintentional weight loss in older adults often precedes Alzheimer’s disease (AD). Positron emission tomography (PET) scan reveals that AD patients exhibit reduced uptake of fluorodeoxyglucose into brain cells, defined as ‘hypometabolism’. However, cellular mechanisms underlying weight loss and hypometabolism have not received much attention. The primary goal of the study was to test the hypothesis that cells become starved in confrontation with amyloid beta proteins (Aβ), which are increasingly aggregated in the AD brain. Cellular ATP is known as a biomarker indicating for cell starvation. We found that Aβ caused a dose-dependent reduction in ATP of astrocytes. This effect was similar to those of cells being deprived from nutrients (i.e., glucose, pyruvate and glutamine). Together, the data of the present study support the hypothesis that cell starvation is likely associated with weight loss and hypometabolism in AD patients.
Show less - Date Issued
- 2022
- PURL
- http://purl.flvc.org/fau/fd/FA00013941
- Subject Headings
- Alzheimer Disease, Amyloid, Amyloid beta-Peptides, Adenosine Triphosphate
- Format
- Document (PDF)
- Title
- Elucidation of a Glial Copper Homeostasis Pathway Regulated by the Caenorhabditis elegans Gene swip-10 with Implications for Systemic Metabolism and Neurodegenerative Disease.
- Creator
- Rodriguez, Peter Jr., Blakely, Randy D., Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Using the Caenorhabditis elegans as a model we have employed forward genetic screens to uncover several novel genetic contributors to dopamine (DA) signaling(1). Follow-up characterization of some of these novel contributors have been detailed in published work from our lab(2), while follow-up studies on other pathways are still underway. Moreover, using the powerful Million Mutation Project library, we have uncovered an important link between primary cilium formation and the regulation of...
Show moreUsing the Caenorhabditis elegans as a model we have employed forward genetic screens to uncover several novel genetic contributors to dopamine (DA) signaling(1). Follow-up characterization of some of these novel contributors have been detailed in published work from our lab(2), while follow-up studies on other pathways are still underway. Moreover, using the powerful Million Mutation Project library, we have uncovered an important link between primary cilium formation and the regulation of the DA transporter dat-1(3). The focus of the body of work detailed in this manuscript is on a glial expressed gene, swip-10, uncovered from our original genetic screen(1, 4, 5). Unlike the other pathways uncovered from our genetic screening, swip-10 does not affect DA signaling via DAT-1 regulation, instead, loss of swip-10 produces excess DA signaling in a glutamate-signaling-dependent manner to cause swimming-induced paralysis (Swip)(4) as well as premature DA neuron degeneration(5). Specifically, the primary aim here was to uncover the molecular pathway by which swip-10 supports these phenotypes.
Show less - Date Issued
- 2024
- PURL
- http://purl.flvc.org/fau/fd/FA00014511
- Subject Headings
- Neurodegenerative Diseases, Glial cells, Caenorhabditis elegans, Copper, Homeostasis
- Format
- Document (PDF)
- Title
- Amyloid Beta Clearance in Alzheimer’s Disease: A PET Imaging and Data Science Study.
- Creator
- Hall, Rudolf, Tao, Rui, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Amyloid beta (Aβ), a byproduct of amyloid precursor protein, is constantly cleared from the CNS. Aβ kinetics are visualized using 18F-florbetapir PET imaging, typically analyzed through 2D coregistration with MRI or CT followed by visual evaluation. Aβ was thought to coexist in the white matter of both Alzheimer’s disease (AD; Aβ+) patients and cognitively unimpaired (CU; Aβ-) individuals. However, this coexistence is likely a misperception of 2D imaging. In this study, data science...
Show moreAmyloid beta (Aβ), a byproduct of amyloid precursor protein, is constantly cleared from the CNS. Aβ kinetics are visualized using 18F-florbetapir PET imaging, typically analyzed through 2D coregistration with MRI or CT followed by visual evaluation. Aβ was thought to coexist in the white matter of both Alzheimer’s disease (AD; Aβ+) patients and cognitively unimpaired (CU; Aβ-) individuals. However, this coexistence is likely a misperception of 2D imaging. In this study, data science techniques were used to evaluate PET images, transforming Aβ imaging into topographical pixel arrays for 3D reconstruction. Canal-like networks in the brain, skull, and neck were discovered to be part of the non-CNS fluid (NCF) compartment, which quarantines Aβ. In CU/Aβ- subjects, Aβ is transported to peripheral lymphatics. In AD/Aβ+ subjects, Aβ becomes congested in the NCF, diffusing into CNS interstitial fluid, leading to progression and neurodegeneration.
Show less - Date Issued
- 2024
- PURL
- http://purl.flvc.org/fau/fd/FA00014531
- Subject Headings
- Alzheimer Disease, Amyloid beta-Peptides, Positron-Emission Tomography
- Format
- Document (PDF)
- Title
- IDENTIFYING EPIGENETIC MODIFICATIONS TO COMBAT RESISTANCE TO THE CHEMOTHERAPEUTIC AGENT DOXORUBICIN.
- Creator
- Kingham, Anna Lesley, Grant, Patrick, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
There has been substantial progress in cancer research that has markedly enhanced patient outcomes. However, chemotherapy resistance persists and often leads to multidrug resistance, rendering cancer cells unresponsive to multiple chemotherapy drugs, presenting a significant challenge in the effective treatment of the disease. Dysregulation in gene expression patterns caused by abnormalities in epigenetic mechanisms have been identified as contributing factors to the development and...
Show moreThere has been substantial progress in cancer research that has markedly enhanced patient outcomes. However, chemotherapy resistance persists and often leads to multidrug resistance, rendering cancer cells unresponsive to multiple chemotherapy drugs, presenting a significant challenge in the effective treatment of the disease. Dysregulation in gene expression patterns caused by abnormalities in epigenetic mechanisms have been identified as contributing factors to the development and progression of cancer. Epigenetic research offers potential to discover drugs that target specific epigenetic modifications to regulate gene expression patterns in the context of chemotherapy resistance. I hypothesize that histone modifications on histone H3 and histone H4 contribute to doxorubicin resistance. The data presented here provides an initial screening of the mutant monoallelic histone yeast strains to identify post-translationally modifiable amino acids in H3 and H4 that could contribute to doxorubicin resistance. The possible targets of histone modifications were then repeated in triplicate to obtain statistical significance. Finally, Western blot techniques were used to identify the modification occurring on the histone H3 and histone H4 amino acid sites that were previously identified to be statistically significant.
Show less - Date Issued
- 2024
- PURL
- http://purl.flvc.org/fau/fd/FA00014473
- Subject Headings
- Epigenetics, Doxorubicin, Chemotherapy
- Format
- Document (PDF)
- Title
- THE ROLE OF ENDOTHELIAL C-MYC IN CARDIAC DYSFUNCTION.
- Creator
- Rahbar, Homan, Rodrigues, Claudia, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Cardiovascular disease is a broad term that encompasses a variety of disorders in which the heart and its associated blood vessels lose the capacity to deliver blood efficiently and effectively throughout the body. Cardiac endothelial cells play a vital role in maintaining the homeostatic balance of cardiac physiology. Research into c-Myc, a master regulator involved in the transcription of a large set of genes that regulate inflammation, has been the focus of new therapeutics aimed at...
Show moreCardiovascular disease is a broad term that encompasses a variety of disorders in which the heart and its associated blood vessels lose the capacity to deliver blood efficiently and effectively throughout the body. Cardiac endothelial cells play a vital role in maintaining the homeostatic balance of cardiac physiology. Research into c-Myc, a master regulator involved in the transcription of a large set of genes that regulate inflammation, has been the focus of new therapeutics aimed at treating or lessening the deleterious effects of cardiovascular disease. This project serves to explore how endothelial loss of c-Myc impacts cardiac function under normal and stress conditions, using ultrasound echocardiography image analysis to determine the key differences between all models.
Show less - Date Issued
- 2024
- PURL
- http://purl.flvc.org/fau/fd/FA00014488
- Subject Headings
- Cardiovascular Diseases, Transcription factors, Endothelial Cells, Echocardiography
- Format
- Document (PDF)
- Title
- Green tea extract catechin improves internal cardiac muscle relaxation in RCM mice.
- Creator
- Wang, Xiaoqin, Zhang, Zhengyu, Wu, Gang, Nan, Changlong, Shen, Wen, Hua, Yimin, Huang, Xupei
- Date Issued
- 2016-12-28
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000199
- Format
- Citation
- Title
- Identification and Ultrastructural Characterization of a Novel Nuclear Degradation Complex in Differentiating Lens Fiber Cells.
- Creator
- Costello, M. Joseph, Brennan, Lisa A., Mohamed, Ashik, Gilliland, Kurt O., Johnsen, Sonke, Kantorow, Marc, Nagaraj, Ram
- Date Issued
- 2016-08-18
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000093
- Format
- Citation
- Title
- Hypothesis: Metalloproteinase Inhibitors Decrease Risks of Cardiovascular Disease.
- Creator
- Lizotte-Waniewski, Michelle, Brew, Keith, Hennekens, Charles H.
- Date Issued
- 2016-07-24
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1177_1074248415615237_1638375551
- Format
- Document (PDF)
- Title
- Region-Specific Regulation of Presynaptic Dopamine Homeostasis by D 2 Autoreceptors Shapes the In Vivo Impact of the Neuropsychiatric Disease-Associated DAT Variant Val559.
- Creator
- Gowrishankar, Raajaram, Gresch, Paul J., Davis, Gwynne L., Katamish, Rania M., Riele, Justin R., Stewart, Adele M., Vaughan, Roxanne A., Hahn, Maureen K., Blakely, Randy D.
- Date Issued
- 2018-05-08
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1523_JNEUROSCI.0055-18.2018_1634583255
- Format
- Citation
- Title
- Entropy Increases from Different Sources Support the High-affinity Binding of the N-terminal Inhibitory Domains of Tissue Inhibitors of Metalloproteinases to the Catalytic Domains of Matrix Metalloproteinases-1 and -3.
- Creator
- Wu, Ying, Wei, Shuo, Van Doren, Steven R., Brew, Keith
- Date Issued
- 2011-05
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1074_jbc.M111.222307_1638299359
- Format
- Document (PDF)
- Title
- Phage Display of Tissue Inhibitor of Metalloproteinases-2 (TIMP-2).
- Creator
- Bahudhanapati, Harinath, Zhang, Yingnan, Sidhu, Sachdev S., Brew, Keith
- Date Issued
- 2011-09
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1074_jbc.M111.253328_1638375138
- Format
- Document (PDF)
- Title
- Thermodynamic Basis of Selectivity in the Interactions of Tissue Inhibitors of Metalloproteinases N-domains with Matrix Metalloproteinases-1, -3, and -14.
- Creator
- Zou, Haiyin, Wu, Ying, Brew, Keith
- Date Issued
- 2016-05
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1074_jbc.M116.720250_1638376717
- Format
- Document (PDF)
- Title
- Family 6 Glycosyltransferases in Vertebrates and Bacteria: Inactivation and Horizontal Gene Transfer May Enhance Mutualism between Vertebrates and Bacteria.
- Creator
- Brew, Keith, Tumbale, Percy, Acharya, K. Ravi
- Date Issued
- 2010-11
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1074_jbc.R110.176248_1638296127
- Format
- Document (PDF)
- Title
- Effects of Charged Cholesterol Derivatives on Aβ40 Amyloid Formation.
- Creator
- Elbassal, Esmail A., Liu, Haiyang, Morris, Clifford, Wojcikiewicz, Ewa P., Du, Deguo
- Date Issued
- 2016-01-14
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1021_acs.jpcb.5b09557_1648064189
- Format
- Document (PDF)
- Title
- Structures of Complexes of a Metal-independent Glycosyltransferase GT6 from Bacteroides ovatus with UDP-N-Acetylgalactosamine (UDP-GalNAc) and Its Hydrolysis Products.
- Creator
- Pham, Tram T.K., Stinson, Brittany, Thiyagarajan, Nethaji, Lizotte-Waniewski, Michelle, Brew, Keith, Acharya, K. Ravi
- Date Issued
- 2014-03
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1074_jbc.M113.545384_1638284195
- Format
- Document (PDF)
- Title
- Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight.
- Creator
- Lybbert, Jared, Gullingsrud, Justin, Chesnokova, Olga, Turyakira, Eleanor, Dhorda, Mehul, Guerin, Philippe J., Piola, Patrice, Muehlenbachs, Atis, Oleinikov, Andrew V.
- Date Issued
- 2016-07-13
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000107
- Format
- Citation
- Title
- Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits.
- Creator
- Muntean, Brian S., Zucca, Stefano, MacMullen, Courtney M., Dao, Maria T., Johnston, Caitlin, Iwamoto, Hideki, Blakely, Randy D., Davis, Ronald L., Martemyanov, Kirill A.
- Date Issued
- 2018-01
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1016_j.celrep.2017.12.022_1634578549
- Format
- Citation
- Title
- p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse.
- Creator
- Robson, Matthew J., Quinlan, Meagan A., Margolis, Kara Gross, Gajewski-Kurdziel, Paula A., Veenstra-VanderWeele, Jeremy, Gershon, Michael D., Watterson, D. Martin, Blakely, Randy D.
- Date Issued
- 2018-10-08
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1073_pnas.1809137115_1634648319
- Format
- Citation
- Title
- Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits.
- Creator
- Brian S. Muntean, Stefano Zucca, Courtney M. MacMullen, Maria T. Dao, Caitlin Johnston, Hideki Iwamoto, Randy D. Blakely, Ronald L. Davis, Kirill A. Martemyanov
- Abstract/Description
-
Modulation of neuronal circuits is key to information processing in the brain. The majority of neuromodulators exert their effects by activating G-proteincoupled receptors (GPCRs) that control the production of second messengers directly impacting cellular physiology. How numerous GPCRs integrate neuromodulatory inputs while accommodating diversity of incoming signals is poorly understood. In this study, we develop an in vivo tool and analytical suite for analyzing GPCR responses by...
Show moreModulation of neuronal circuits is key to information processing in the brain. The majority of neuromodulators exert their effects by activating G-proteincoupled receptors (GPCRs) that control the production of second messengers directly impacting cellular physiology. How numerous GPCRs integrate neuromodulatory inputs while accommodating diversity of incoming signals is poorly understood. In this study, we develop an in vivo tool and analytical suite for analyzing GPCR responses by monitoring the dynamics of a key second messenger, cyclic AMP (cAMP), with excellent quantitative and spatiotemporal resolution in various neurons. Using this imaging approach in combination with CRISPR/Cas9 editing and optogenetics, we interrogate neuromodulatory mechanisms of defined populations of neurons in an intact mesolimbic reward circuit and describe how individual inputs generate discrete second-messenger signatures in a cell- and receptor- specific fashion. This offers a resource for studying native neuronal GPCR signaling in real time.
Show less - Date Issued
- 2018
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000525
- Format
- Document (PDF)
- Title
- Is dopamine transporter-mediated dopaminergic signaling in the retina a noninvasive biomarker for attention-deficit/ hyperactivity disorder? A study in a novel dopamine transporter variant Val559 transgenic mouse model.
- Creator
- Dai, Heng, Jackson, Chad R., Davis, Gwynne L., Blakely, Randy D., McMahon, Douglas G.
- Date Issued
- 2017-12-28
- PURL
- http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1186_s11689-017-9215-8_1634318373
- Format
- Citation