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Articles 1 - 13 of 13
Full-Text Articles in Medicine and Health Sciences
Differentially Disrupted Spinal Cord And Muscle Energy Metabolism In Spinal And Bulbar Muscular Atrophy, Danielle Debartolo, Frederick Arnold, Y Liu, Elana Molotsky, Hsin-Yao Tang, Diane Merry
Differentially Disrupted Spinal Cord And Muscle Energy Metabolism In Spinal And Bulbar Muscular Atrophy, Danielle Debartolo, Frederick Arnold, Y Liu, Elana Molotsky, Hsin-Yao Tang, Diane Merry
Department of Biochemistry and Molecular Biology Faculty Papers
Prior studies showed that polyglutamine-expanded androgen receptor (AR) is aberrantly acetylated and that deacetylation of the mutant AR by overexpression of nicotinamide adenine dinucleotide-dependent (NAD+-dependent) sirtuin 1 is protective in cell models of spinal and bulbar muscular atrophy (SBMA). Based on these observations and reduced NAD+ in muscles of SBMA mouse models, we tested the therapeutic potential of NAD+ restoration in vivo by treating postsymptomatic transgenic SBMA mice with the NAD+ precursor nicotinamide riboside (NR). NR supplementation failed to alter disease progression and had no effect on increasing NAD+ or ATP content in muscle, despite producing a modest increase of …
Novel Treatments For Pxe: Targeting The Systemic And Local Drivers Of Ectopic Calcification, Ida Joely Jacobs, Qiaoli Li
Novel Treatments For Pxe: Targeting The Systemic And Local Drivers Of Ectopic Calcification, Ida Joely Jacobs, Qiaoli Li
Department of Biochemistry and Molecular Biology Faculty Papers
Pseudoxanthoma elasticum (PXE) is a heritable multisystem ectopic calcification disorder. The gene responsible for PXE, ABCC6, encodes ABCC6, a hepatic efflux transporter regulating extracellular inorganic pyrophosphate (PPi), a potent endogenous calcification inhibitor. Recent studies demonstrated that in addition to the deficiency of plasma PPi, the activated DDR/PARP signaling in calcified tissues provides an additional possible mechanism of ectopic calcification in PXE. This study examined the effects of etidronate (ETD), a stable PPi analog, and its combination with minocycline (Mino), a potent inhibitor of DDR/PARP, on ectopic calcification in an Abcc6-/- mouse model of PXE. Abcc6-/- mice, at 4 weeks of …
Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews
Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews
Tyler Johnson
Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged …
Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M Vaske, Kimberly N White, Tanya L Cohen, Helene C Vervoort, Karen Tenney, Frederick A Valeriote, Leonard F Bjeldanes, Phillip Crews
Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M Vaske, Kimberly N White, Tanya L Cohen, Helene C Vervoort, Karen Tenney, Frederick A Valeriote, Leonard F Bjeldanes, Phillip Crews
Tyler Johnson
A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E' (13) and F' (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship …
Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F Bjeldanes, Keith Rayburn
Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F Bjeldanes, Keith Rayburn
Tyler Johnson
Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate …
Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor
Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor
Janet M. Stavnezer
Several proteins in the BRCA-Fanconi anemia (FA) pathway, such as FANCJ, BRCA1, and FANCD2, interact with mismatch repair (MMR) pathway factors, but the significance of this link remains unknown. Unlike the BRCA-FA pathway, the MMR pathway is not essential for cells to survive toxic DNA interstrand crosslinks (ICLs), although MMR proteins bind ICLs and other DNA structures that form at stalled replication forks. We hypothesized that MMR proteins corrupt ICL repair in cells that lack crosstalk between BRCA-FA and MMR pathways. Here, we show that ICL sensitivity of cells lacking the interaction between FANCJ and the MMR protein MLH1 is …
Hnrnp A1 And Secondary Structure Coordinate Alternative Splicing Of Mag, Nancy Zearfoss, Emily Johnson, Sean Ryder
Hnrnp A1 And Secondary Structure Coordinate Alternative Splicing Of Mag, Nancy Zearfoss, Emily Johnson, Sean Ryder
Sean P. Ryder
Myelin-associated glycoprotein (MAG) is a major component of myelin in the vertebrate central nervous system. MAG is present in the periaxonal region of the myelin structure, where it interacts with neuronal proteins to inhibit axon outgrowth and protect neurons from degeneration. Two alternatively spliced isoforms of Mag mRNA have been identified. The mRNA encoding the shorter isoform, known as S-MAG, contains a termination codon in exon 12, while the mRNA encoding the longer isoform, known as L-MAG, skips exon 12 and produces a protein with a longer C-terminal region. L-MAG is required in the central nervous system. How inclusion of …
Coprinus Comatus Cap Inhibits Adipocyte Differentiation Via Regulation Of Pparγ And Akt Signaling Pathway, Hyoung Joon Park, Jisoo Yun, Hong-Duck Kim, Chung-Kil Won, Gon-Sup Kim, Jae-Hyeon Cho
Coprinus Comatus Cap Inhibits Adipocyte Differentiation Via Regulation Of Pparγ And Akt Signaling Pathway, Hyoung Joon Park, Jisoo Yun, Hong-Duck Kim, Chung-Kil Won, Gon-Sup Kim, Jae-Hyeon Cho
NYMC Faculty Publications
This study assessed the effects of Coprinus comatus cap (CCC) on adipogenesis in 3T3-L1 adipocytes and the effects of CCC on the development of diet-induced obesity in rats. Here, we showed that the CCC has an inhibitory effect on the adipocyte differentiation of 3T3-L1 cells, resulting in a significant decrease in lipid accumulation through the downregulation of several adipocyte specific-transcription factors, including CCAAT/enhancer binding protein β, C/EBPδ, and peroxisome proliferator-activated receptor gamma (PPARγ). Moreover, treatment with CCC during adipocyte differentiation induced a significant down-regulation of PPARγ and adipogenic target genes, including adipocyte protein 2, lipoprotein lipase, and adiponectin. Interestingly, the …
Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair
Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair
Dartmouth Scholarship
The spread of drug-resistant bacterial pathogens is a growing global concern and has prompted an effort to explore potential adjuvant and alternative therapies derived from nature's repertoire of bactericidal proteins and peptides. In humans, the airway surface liquid layer is a rich source of antibiotics, and lysozyme represents one of the most abundant and effective antimicrobial components of airway secretions. Human lysozyme is active against both Gram-positive and Gram-negative bacteria, ac
Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F. Bjeldanes, Keith Rayburn
Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F. Bjeldanes, Keith Rayburn
Natural Sciences and Mathematics | Faculty Scholarship
Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate …
Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M. Vaske, Kimberly N. White, Tanya L. Cohen, Helene C. Vervoort, Karen Tenney, Frederick A. Valeriote, Leonard F. Bjeldanes, Phillip Crews
Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M. Vaske, Kimberly N. White, Tanya L. Cohen, Helene C. Vervoort, Karen Tenney, Frederick A. Valeriote, Leonard F. Bjeldanes, Phillip Crews
Natural Sciences and Mathematics | Faculty Scholarship
A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E' (13) and F' (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship …
Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews
Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews
Natural Sciences and Mathematics | Faculty Scholarship
Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged …
Atf4 Is An Oxidative Stress–Inducible, Prodeath Transcription Factor In Neurons In Vitro And In Vivo, Philipp Lange, Juan Chavez, John T. Pinto, Giovanni Coppola, Chiao-Wang Sun, Tim Townes, Rajiv Ratan
Atf4 Is An Oxidative Stress–Inducible, Prodeath Transcription Factor In Neurons In Vitro And In Vivo, Philipp Lange, Juan Chavez, John T. Pinto, Giovanni Coppola, Chiao-Wang Sun, Tim Townes, Rajiv Ratan
NYMC Faculty Publications
Oxidative stress is pathogenic in neurological diseases, including stroke. The identity of oxidative stress-inducible transcription factors and their role in propagating the death cascade are not well known. In an in vitro model of oxidative stress, the expression of the bZip transcription factor activating transcription factor 4 (ATF4) was induced by glutathione depletion and localized to the promoter of a putative death gene in neurons. Germline deletion of ATF4 resulted in a profound reduction in oxidative stress-induced gene expression and resistance to oxidative death. In neurons, ATF4 modulates an early, upstream event in the death pathway, as resistance to oxidative …