Open Access. Powered by Scholars. Published by Universities.®

Amino Acids, Peptides, and Proteins Commons™

Open Access. Powered by Scholars. Published by Universities.®

2017

Discipline
Institution
Keyword
Publication
Publication Type

Articles 31 - 60 of 75

Full-Text Articles in Amino Acids, Peptides, and Proteins

Chloroformate Derivatization For Tracing The Fate Of Amino Acids In Cells And Tissues By Multiple Stable Isotope Resolved Metabolomics (Msirm), Ye Yang, Teresa W. -M. Fan, Andrew N. Lane, Richard M. Higashi Jul 2017

Chloroformate Derivatization For Tracing The Fate Of Amino Acids In Cells And Tissues By Multiple Stable Isotope Resolved Metabolomics (Msirm), Ye Yang, Teresa W. -M. Fan, Andrew N. Lane, Richard M. Higashi

Center for Environmental and Systems Biochemistry Faculty Publications

Amino acids have crucial roles in central metabolism, both anabolic and catabolic. To elucidate these roles, steady-state concentrations of amino acids alone are insufficient, as each amino acid participates in multiple pathways and functions in a complex network, which can also be compartmentalized. Stable Isotope-Resolved Metabolomics (SIRM) is an approach that uses atom-resolved tracking of metabolites through biochemical transformations in cells, tissues, or whole organisms. Using different elemental stable isotopes to label multiple metabolite precursors makes it possible to resolve simultaneously the utilization of these precursors in a single experiment. Conversely, a single precursor labeled with two (or more) different …

Go to article

Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried Jul 2017

Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

Human O6-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O6-alkylguanine and O4-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein–protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ωave. We found …

Go to article

Abnormal Dendritic Maturation Of Developing Cortical Neurons Exposed To Corticotropin Releasing Hormone (Crh): Insights Into Effects Of Prenatal Adversity?, Megan M. Curran, Curt A. Sandman, Elyssia Poggi Davis, Laura M. Glynn, Tallie Z. Baram Jun 2017

Abnormal Dendritic Maturation Of Developing Cortical Neurons Exposed To Corticotropin Releasing Hormone (Crh): Insights Into Effects Of Prenatal Adversity?, Megan M. Curran, Curt A. Sandman, Elyssia Poggi Davis, Laura M. Glynn, Tallie Z. Baram

Psychology Faculty Articles and Research

Corticotropin releasing hormone (CRH) produced by the hypothalamus initiates the hypothalamic- pituitary-adrenal (HPA) axis, which regulates the body's stress response. CRH levels typically are undetectable in human plasma, but during pregnancy the primate placenta synthesizes and releases large amounts of CRH into both maternal and fetal circulations. Notably, placental CRH synthesis increases in response to maternal stress signals. There is evidence that human fetal exposure to high concentrations of placental CRH is associated with behavioral consequences during infancy and into childhood, however the direct effects on of the peptide on the human brain are unknown. In this study, we used …

Go to article

Mechanical Stability Of Talin Rod Controls Cell Migration And Substrate Sensing, Rolle Rahikainen, Magdaléna Von Essen, Markus Schaefer, Lei Qi, Latifeh Azizi, Conor Kelly, Teemu O. Ihalainen, Bernhard Wehrle-Haller, Martin Bastmeyer, Cai Huang, Vesa P. Hytönen Jun 2017

Mechanical Stability Of Talin Rod Controls Cell Migration And Substrate Sensing, Rolle Rahikainen, Magdaléna Von Essen, Markus Schaefer, Lei Qi, Latifeh Azizi, Conor Kelly, Teemu O. Ihalainen, Bernhard Wehrle-Haller, Martin Bastmeyer, Cai Huang, Vesa P. Hytönen

Markey Cancer Center Faculty Publications

Cells adhere to the surrounding tissue and probe its mechanical properties by forming cell-matrix adhesions. Talin is a critical adhesion protein and participates in the transmission of mechanical signals between extracellular matrix and cell cytoskeleton. Force induced unfolding of talin rod subdomains has been proposed to act as a cellular mechanosensor, but so far evidence linking their mechanical stability and cellular response has been lacking. Here, by utilizing computationally designed mutations, we demonstrate that stepwise destabilization of the talin rod R3 subdomain decreases cellular traction force generation, which affects talin and vinculin dynamics in cell-matrix adhesions and results in the …

Go to article

Synthesis And Evaluation Of Antimicrobial Activity Of [R4w4k]-Levofloxacin And [R4w4k]-Levofloxacin-Q Conjugates, Neda Riahifard, Kathy Tavakoli, Jason Yamaki, Keykavous Parang, Rakesh Tiwari Jun 2017

Synthesis And Evaluation Of Antimicrobial Activity Of [R4w4k]-Levofloxacin And [R4w4k]-Levofloxacin-Q Conjugates, Neda Riahifard, Kathy Tavakoli, Jason Yamaki, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that the amphiphilic cyclic peptide [R4W4] had antibacterial activity with a minimum inhibitory concentration (MIC) of 2.97 g/mL against Methicillin-resistant Staphylococcus aureus (MRSA). Herein, we hypothesized that conjugation or combination of the amphiphilic cyclic peptide [R4W4] with levofloxacin or levofloxacin-Q could improve the antibacterial activity of levofloxacin and levofloxacin-Q. Fmoc/tBu solid-phase chemistry was employed to synthesize conjugates of …

Go to article

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips May 2017

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

Go to article

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana May 2017

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)2 has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)2 sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption …

Go to article

Kinetic Studies Of Dna Repair Enzyme Alkbh2, Michael R. Vittori May 2017

Kinetic Studies Of Dna Repair Enzyme Alkbh2, Michael R. Vittori

Senior Honors Projects

The genomes of living organisms are under constant bombardment from various sources, including chemical modification stemming from processes within the organisms themselves or from exogenous agents, and from radiation. These sources of genomic damage may induce structural changes in the genome’s most basic functional units, the nucleotides that comprise DNA. Damage to an organism’s DNA may result in the production of dysfunctional or nonfunctional proteins. Failure to repair such damage may result in the compounding of successive mutations within the organism’s genome, the pathogenesis of cancer and various genetic disorders in humans. To ensure their viability, organisms have developed unique …

Go to article

Novel Effects Of Prefoldin Pathway On Intestinal Homeostasis Via Dietary Restriction In Drosophila Melanogaster, Jesse Simons May 2017

Novel Effects Of Prefoldin Pathway On Intestinal Homeostasis Via Dietary Restriction In Drosophila Melanogaster, Jesse Simons

Dissertations, Masters Theses, Capstones, and Culminating Projects

The field of medicine research is embroiled in a battle against aging. Particular focus is on the extension of lifespan and health-span. Lifespan duration is affected by many factors, one of which is the maintenance of the intestines of the organism. Homeostasis of the intestines is controlled by the regulation of intestine cell apoptosis and intestine cell proliferation. My research explores the role of two protein subunits found in a complex which may have possible functions in the regulation of these processes. The overall complex is formed from six subunit proteins, some of which are known to assist in other …

Go to article

Recombinant Expression And Purification Of Amyloid-Β In E. Coli, Wisam M. Beauti May 2017

Recombinant Expression And Purification Of Amyloid-Β In E. Coli, Wisam M. Beauti

Honors Theses

Alzheimer’s disease (AD) is a common neurodegenerative disorder that affects people older than 65 years 1,2,5. It is characterized by the presence of extracellular plaque deposits that are seen specifically in the brains of AD patients 4,5. These plaques are mainly comprised of amyloid-β (Aβ) peptide aggregates. Aβ plaque production and deposition is believed to drive AD pathogenesis. Studying these proteins is crucial to understanding aspects of AD in order to develop possible therapeutic treatments. Recombinant expression of Aβ can also provide a handle to introduce mutations in the protein to further study their structure-function relationships. However, synthetic Aβ monomer …

Go to article

Melatonin And Its Metabolites Protect Human Melanocytes Against Uvb-Induced Damage: Involvement Of Nrf2-Mediated Pathways, Zorica Janjetovic, Stuart G. Jarrett, Elizabeth F. Lee, Cory Duprey, Russel J. Reiter, Andrzej T. Slominski Apr 2017

Melatonin And Its Metabolites Protect Human Melanocytes Against Uvb-Induced Damage: Involvement Of Nrf2-Mediated Pathways, Zorica Janjetovic, Stuart G. Jarrett, Elizabeth F. Lee, Cory Duprey, Russel J. Reiter, Andrzej T. Slominski

Toxicology and Cancer Biology Faculty Publications

Ultraviolet light (UV) is an inducer of reactive oxygen species (ROS) as well as 6-4-photoproducts and cyclobutane pyrimidine dimers (CPD) in the skin, which further cause damage to the skin cells. Irradiation of cultured human melanocytes with UVB stimulated ROS production, which was reduced in cells treated with melatonin or its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), and 5-methoxytryptamine (5-MT). Melatonin and its derivatives also stimulated the expression of NRF2 (nuclear factor erythroid 2 [NF-E2]-related factor 2) and its target enzymes and proteins that play an important role in cell protection from different damaging factors including UVB. Silencing …

Go to article

Nucleic Acid Combinations: A New Frontier For Cancer Treatment, K. C. Remant Bahadur, Bindu Thapa, Juliana Valencia-Serna, Hamidreza Montazeri Aliabadi, Hasan Uludağ Apr 2017

Nucleic Acid Combinations: A New Frontier For Cancer Treatment, K. C. Remant Bahadur, Bindu Thapa, Juliana Valencia-Serna, Hamidreza Montazeri Aliabadi, Hasan Uludağ

Pharmacy Faculty Articles and Research

The emerging molecular understanding of cancer cell behavior is leading to increasing possibilities to control unchecked cell growth and metastasis. On the other hand, development of multifunctional drug carriers at the ‘nano’-scale is providing exciting new therapeutic strategies in clinical management of cancer beyond the conventional cytotoxic drugs. A new frontier in this regard is the combinational use of complementary agents based on nucleic acids to overcome the limitations of conventional therapy. The existence of tightly-integrated cross-talk through multiple signaling and effector pathways has been appreciated for some time, and the plasticity of such a network to overcome one-dimensional intervention …

Go to article

Npy1 Receptor Agonist Modulates Development Of Depressive-Like Behavior And Gene Expression In Hypothalamus In Sps Rodent Ptsd Model, Lidia Serova, H Mulhall, Esther Sabban Apr 2017

Npy1 Receptor Agonist Modulates Development Of Depressive-Like Behavior And Gene Expression In Hypothalamus In Sps Rodent Ptsd Model, Lidia Serova, H Mulhall, Esther Sabban

NYMC Faculty Publications

Delivery of neuropeptide Y (NPY) to the brain by intranasal infusion soon after traumatic stress has shown therapeutic potential, and prevented development of many behavioral and neuroendocrine impairments in the single prolonged stress (SPS) animal model of PTSD. Therefore, we examined whether the Y1R preferring agonist [Leu(31)Pro(34)]NPY is sufficient to prevent development of SPS induced depressive-like behavioral changes, and hypothalamic gene expression as obtained with intranasal NPY intervention. Male Sprague-Dawely rats were given intranasal infusion of either NPY (150 mug/rat), a low (68 mug /rat), or high (132 mug/rat) dose of [Leu(31)Pro(34)]NPY or vehicle immediately following the last SPS stressor, …

Go to article

Gene 33/Mig6 Regulates Apoptosis And The Dna Damage Response Through Independent Mechanisms, Cen Li, Soyoung Park, Leonard M. Eisenberg, Hong Zhao, Zbigniew Darzynkiewicz, Dazhong Xu Mar 2017

Gene 33/Mig6 Regulates Apoptosis And The Dna Damage Response Through Independent Mechanisms, Cen Li, Soyoung Park, Leonard M. Eisenberg, Hong Zhao, Zbigniew Darzynkiewicz, Dazhong Xu

NYMC Faculty Posters

Gene 33 (Mig6, ERRFI1) is an inducible adaptor/scaffold protein whose expression can be induced by both stress and mitogenic signals. It contains multiple domains for protein-protein interaction and is involved in a broad spectrum of cellular functions. Gene 33 promotes apoptosis in a cell type-dependent manner. A recent study has linked Gene 33 to the DNA damage response (DDR) induced by hexavalent chromium [Cr(VI)]. Here we show that Gene 33 induces apoptosis via both c-Abl/p73 and EGFR/AKT-dependent pathways in lung epithelial and lung carcinoma cells. Ectopic expression of Gene 33 also triggers DDR in an ATM-dependent fashion and through pathways …

Go to article

Targeted Aav5-Smad7 Gene Therapy Inhibits Corneal Scarring In Vivo, Suneel Gupta, Jason T. Rodier, Ajay Sharma, Elizabeth A. Giuliano, Prashant R. Sinha, Nathan P. Hesemann, Arkasubhra Ghosh, Rajiv R. Mohan Mar 2017

Targeted Aav5-Smad7 Gene Therapy Inhibits Corneal Scarring In Vivo, Suneel Gupta, Jason T. Rodier, Ajay Sharma, Elizabeth A. Giuliano, Prashant R. Sinha, Nathan P. Hesemann, Arkasubhra Ghosh, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring. Hence, therapeutic targets that reduce transdifferentiation of fibroblasts into myofibroblasts may provide a clinically relevant approach to treat corneal fibrosis and improve long-term visual outcomes. Smad7 protein regulates the functional effects of TGFβ signaling …

Go to article

Are Gene Polymorphisms Of Fibroblast Growth Factor 10 Associated With Patent Ductus Arteriosus And Bronchopulmonary Dysplasia In Extremely Low Birth Weight Infants?, Shaili Amatya, Asma Amin, Umesh Paudel, Lance A. Parton Mar 2017

Are Gene Polymorphisms Of Fibroblast Growth Factor 10 Associated With Patent Ductus Arteriosus And Bronchopulmonary Dysplasia In Extremely Low Birth Weight Infants?, Shaili Amatya, Asma Amin, Umesh Paudel, Lance A. Parton

NYMC Faculty Posters

No abstract provided.

Go to article

Synthesis And Anti-Hiv Activities Of Unsymmetrical Long Chain Dicarboxylate Esters Of Dinucleosides Reverse Transcriptase Inhibitors, Hitesh K. Agarwal, Bhupender S. Chhikara, Gustavo F. Doncel, Keykavous Parang Mar 2017

Synthesis And Anti-Hiv Activities Of Unsymmetrical Long Chain Dicarboxylate Esters Of Dinucleosides Reverse Transcriptase Inhibitors, Hitesh K. Agarwal, Bhupender S. Chhikara, Gustavo F. Doncel, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of 11 unsymmetrical dinucleoside dicarboxylate conjugates of nucleoside reverse transcriptase inhibitors were synthesized. Three dicarboxylic acids, succinic acid, suberic acid and 1,14-tetradecandioc acid, were diesterified with either 3'-azido- 2',3'-dideoxythymidine (AZT), 3'-fluoro-2',3'-dideoxythymidine (FLT), 2',3'-dideoxy-3'-thiacytidine (3TC) or 5-fluoro-2',3'-dideoxy-3'- thiacytidine (FTC). The anti-HIV activity of synthesized compounds was evaluated against HIV-1 X4 (IIIB) and R5 (BaL) viral strains in single-round infection assays. Results indicated that the tetradecandioate esters of nucleosides were more active against HIV than the corresponding parent nucleosides and nucleoside conjugates. The tetradecandioate conjugate of FLT and FTC (5) was found to be the most potent compound with EC50 …

Go to article

Aberrant Coordination Geometries Discovered In The Most Abundant Metalloproteins, Sen Yao, Robert M. Flight, Eric C. Rouchka, Hunter N. B. Moseley Mar 2017

Aberrant Coordination Geometries Discovered In The Most Abundant Metalloproteins, Sen Yao, Robert M. Flight, Eric C. Rouchka, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Metalloproteins bind and utilize metal ions for a variety of biological purposes. Due to the ubiquity of metalloprotein involvement throughout these processes across all domains of life, how proteins coordinate metal ions for different biochemical functions is of great relevance to understanding the implementation of these biological processes. Toward these ends, we have improved our methodology for structurally and functionally characterizing metal binding sites in metalloproteins. Our new ligand detection method is statistically much more robust, producing estimated false positive and false negative rates of ∼0.11% and ∼1.2%, respectively. Additional improvements expand both the range of metal ions and their …

Go to article

Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch Mar 2017

Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch

UNO Student Research and Creative Activity Fair

Phosphatidylinositol 3-kinases (PI3Ks) and their related pathways are reputed targets for drug-based anticancer therapies. Mutations in PI3K genes, expression, and pathways are frequent among multiple cancer types. Four isoforms of PI3Ks exist: α, β, γ, & δ and studies have identified several ligands for each isoform which are capable of serving as inhibitory therapeutic compounds. However, the biochemical efficacy of these molecules varies and the isoform selectivity is not well understood. In this study, we applied in silico docking methods and free energy calculation methods to estimate the binding of reported PI3K ligands against 5 PI3K structures: PI3Kα (PBD ID: …

Go to article

Pnaktide Attenuates Steatohepatitis And Atherosclerosis By Blocking Na/K-Atpase/Ros Amplification In C57bi6 And Apoe Knockout Mice Fed A Western Diet, Komal Sodhi, K Srikanthan, P Goguet-Rubio, A Nichols, A Mallick, A Nawab, R Martin, P Shah, M Chaudhry, S Sigdel, M El-Hamdani, J Liu, Z Xie, Nader Abraham, J Shapiro Mar 2017

Pnaktide Attenuates Steatohepatitis And Atherosclerosis By Blocking Na/K-Atpase/Ros Amplification In C57bi6 And Apoe Knockout Mice Fed A Western Diet, Komal Sodhi, K Srikanthan, P Goguet-Rubio, A Nichols, A Mallick, A Nawab, R Martin, P Shah, M Chaudhry, S Sigdel, M El-Hamdani, J Liu, Z Xie, Nader Abraham, J Shapiro

NYMC Faculty Publications

We have previously reported that the alpha1 subunit of sodium potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a "western" diet containing high amounts of fat and fructose. The administration of pNaKtide reduced obesity as well as hepatic steatosis, inflammation and fibrosis. Of interest, we also noted …

Go to article

Hendra Virus Fusion Protein Transmembrane Domain Contributes To Pre-Fusion Protein Stability, Stacy Webb, Tamas Nagy, Hunter Moseley, Michael G. Fried, Rebecca Ellis Dutch Feb 2017

Hendra Virus Fusion Protein Transmembrane Domain Contributes To Pre-Fusion Protein Stability, Stacy Webb, Tamas Nagy, Hunter Moseley, Michael G. Fried, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains …

Go to article

Dual-Functional-Tag-Facilitated Protein Labeling And Immobilization, Xinyi Zhang, Wei Lu, Kevin Kwan, Dibakar Bhattacharyya, Yinan Wei Feb 2017

Dual-Functional-Tag-Facilitated Protein Labeling And Immobilization, Xinyi Zhang, Wei Lu, Kevin Kwan, Dibakar Bhattacharyya, Yinan Wei

Chemistry Faculty Publications

An important strategy in the construction of biomimetic membranes and devices is to use natural proteins as the functional components for incorporation in a polymeric or nanocomposite matrix. Toward this goal, an important step is to immobilize proteins with high efficiency and precision without disrupting the protein function. Here, we developed a dual-functional tag containing histidine and the non-natural amino acid azidohomoalanine (AHA). AHA is metabolically incorporated into the protein, taking advantage of the Met-tRNA and Met-tRNA synthetase. Histidine in the tag can facilitate metal-affinity purification, whereas AHA can react with an alkyne-functionalized probe or surface via well-established click chemistry. …

Go to article

Osteoblast-Derived Fgf9 Regulates Skeletal Homeostasis, Liping Wang, Theresa M. Roth, Marcia J. Abbott, Linh Ho, Lalita Wattanachanya, Robert A. Nissenson Feb 2017

Osteoblast-Derived Fgf9 Regulates Skeletal Homeostasis, Liping Wang, Theresa M. Roth, Marcia J. Abbott, Linh Ho, Lalita Wattanachanya, Robert A. Nissenson

Health Sciences and Kinesiology Faculty Articles

FGF9 has complex and important roles in skeletal development and repair. We have previously observed that Fgf9 expression in osteoblasts (OBs) is regulated by G protein signaling and therefore the present study was done to determine whether OB-derived FGF9 was important in skeletal homeostasis. To directly test this idea, we deleted functional expression of Fgf9 gene in OBs using a 2.3 kb collagen type I promoter-driven Cre transgenic mouse line (Fgf9OB −/−). Both Fgf9 knockout (Fgf9OB −/−) and the Fgf9 floxed littermates (Fgf9fl/fl) mice were fully backcrossed and maintained in an FBV/N background. Three …

Go to article

Editing Of Misaminoacylated Trna Controls The Sensitivity Of Amino Acid Stress Responses In Saccharomyces Cerevisiae, Kyle Mohler, Rebecca Mann, Tammy J. Bullwinkle, Kyle W. Hopkins, Lin Hwang, Noah M. Reynolds, Brandon Gassaway, Hans-Rudolph Aerni, Jesse Rinehart, Michael Polymenis, Kym F. Faull, Michael Ibba Feb 2017

Editing Of Misaminoacylated Trna Controls The Sensitivity Of Amino Acid Stress Responses In Saccharomyces Cerevisiae, Kyle Mohler, Rebecca Mann, Tammy J. Bullwinkle, Kyle W. Hopkins, Lin Hwang, Noah M. Reynolds, Brandon Gassaway, Hans-Rudolph Aerni, Jesse Rinehart, Michael Polymenis, Kym F. Faull, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Amino acid starvation activates the protein kinase Gcn2p, leading to changes in gene expression and translation. Gcn2p is activated by deacylated tRNA, which accumulates when tRNA aminoacylation is limited by lack of substrates or inhibition of synthesis. Pairing of amino acids and deacylated tRNAs is catalyzed by aminoacyl-tRNA synthetases, which use quality control pathways to maintain substrate specificity. Phenylalanyl-tRNA synthetase (PheRS) maintains specificity via an editing pathway that targets non-cognate Tyr-tRNAPhe. While the primary role of aaRS editing is to prevent misaminoacylation, we demonstrate editing of misaminoacylated tRNA is also required for detection of amino acid starvation by …

Go to article

Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van Der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal Feb 2017

Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van Der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal

Genomics and Precision Medicine Faculty Publications

Dystrophin deficiency is the genetic basis for Duchenne muscular dystrophy (DMD), but the cellular basis of progressive myofiber death in DMD is not fully understood. Using two dystrophin-deficient mdx mouse models, we find that the mitochondrial dysfunction is among the earliest cellular deficits of mdx muscles. Mitochondria in dystrophic myofibers also respond poorly to sarcolemmal injury. These mitochondrial deficits reduce the ability of dystrophic muscle cell membranes to repair and are associated with a compensatory increase in dysferlin-mediated membrane repair proteins. Dysferlin deficit in mdx mice further compromises myofiber cell membrane repair and enhances the muscle pathology at an asymptomatic …

Go to article

Quality Control By Isoleucyl-Trna Synthetase Of Bacillus Subtilis Is Required For Efficient Sporulation, Elizabeth Kermgard, Zhou Yang, Annika-Marisa Michel, Rachel Simari, Jacqueline Wong, Michael Ibba, Beth A. Lazazzera Jan 2017

Quality Control By Isoleucyl-Trna Synthetase Of Bacillus Subtilis Is Required For Efficient Sporulation, Elizabeth Kermgard, Zhou Yang, Annika-Marisa Michel, Rachel Simari, Jacqueline Wong, Michael Ibba, Beth A. Lazazzera

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Isoleucyl-tRNA synthetase (IleRS) is an aminoacyl-tRNA synthetase whose essential function is to aminoacylate tRNAIle with isoleucine. Like some other aminoacyl-tRNA synthetases, IleRS can mischarge tRNAIle and correct this misacylation through a separate post-transfer editing function. To explore the biological significance of this editing function, we created a ileS(T233P) mutant of Bacillus subtilis that allows tRNAIle mischarging while retaining wild-type Ile-tRNAIle synthesis activity. As seen in other species defective for aminoacylation quality control, the growth rate of the ileS(T233P) strain was not significantly different from wild-type. When the ileS(T233P) strain was assessed for its ability to promote …

Go to article

Ms-Read: Quantitative Measurement Of Amino Acid Incorporation, Kyle Mohler, Hans-Rudolph Aerni, Brandon Gassaway, Jiqiang Ling, Michael Ibba, Jesse Rinehart Jan 2017

Ms-Read: Quantitative Measurement Of Amino Acid Incorporation, Kyle Mohler, Hans-Rudolph Aerni, Brandon Gassaway, Jiqiang Ling, Michael Ibba, Jesse Rinehart

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Ribosomal protein synthesis results in the genetically programmed incorporation of amino acids into a growing polypeptide chain. Faithful amino acid incorporation that accurately reflects the genetic code is critical to the structure and function of proteins as well as overall proteome integrity. Errors in protein synthesis are generally detrimental to cellular processes yet emerging evidence suggest that proteome diversity generated through mistranslation may be beneficial under certain conditions. Cumulative translational error rates have been determined at the organismal level, however codon specific error rates and the spectrum of misincorporation errors from system to system remain largely unexplored. In particular, until …

Go to article

Computational Analysis Of Residue Interaction Networks And Coevolutionary Relationships In The Hsp70 Chaperones: A Community- Hopping Model Of Allosteric Regulation And Communication, Gabrielle Stetz, Gennady M. Verkhivker Jan 2017

Computational Analysis Of Residue Interaction Networks And Coevolutionary Relationships In The Hsp70 Chaperones: A Community- Hopping Model Of Allosteric Regulation And Communication, Gabrielle Stetz, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks …

Go to article

Maysin And Its Flavonoid Derivative From Centipedegrass Attenuates Amyloid Plaques By Inducting Humoral Immune Response With Th2 Skewed Cytokine Response In The Tg (Appswe, Ps1de9) Alzheimer's Mouse Model, Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Seung Sik Lee, Jae-Hyeon Cho Jan 2017

Maysin And Its Flavonoid Derivative From Centipedegrass Attenuates Amyloid Plaques By Inducting Humoral Immune Response With Th2 Skewed Cytokine Response In The Tg (Appswe, Ps1de9) Alzheimer's Mouse Model, Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Seung Sik Lee, Jae-Hyeon Cho

NYMC Faculty Publications

Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. In a previous study, we found that an ethyl acetate extract of Centipedegrass (CG) (i.e., EA-CG) contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ) by inhibiting oligomeric Aβ in cellular and in vitro models. Here, we examined the preventative effects of EA-CG treatment on the Aβ burden in the Tg (Mo/Hu APPswe PS1dE9) AD mouse model. We …

Go to article

Inhibition Of Mammalian Glycoprotein Ykl-40 Identification Of The Physiological Ligand, Abhishek A. Kognole, Christina M. Payne Jan 2017

Inhibition Of Mammalian Glycoprotein Ykl-40 Identification Of The Physiological Ligand, Abhishek A. Kognole, Christina M. Payne

Chemical and Materials Engineering Faculty Publications

YKL-40 is a mammalian glycoprotein associated with progression, severity, and prognosis of chronic inflammatory diseases and a multitude of cancers. Despite this well documented association, identification of the lectin′s physiological ligand and, accordingly, biological function has proven experimentally difficult. YKL-40 has been shown to bind chito-oligosaccharides; however, the production of chitin by the human body has not yet been documented. Possible alternative ligands include proteoglycans, polysaccharides, and fibers like collagen, all of which makeup the extracellular matrix. It is likely that YKL-40 is interacting with these alternative polysaccharides or proteins within the body, extending its function to cell biological roles …

Go to article

First Prev Next Last