Medical Biochemistry Commons^™

Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough

Kevin M Rice

The effects of ageing on the cardiovascular system contribute to substantial alterations in cellular morphology and function. The variables regulating these changes are unknown; however, one set of signalling molecules that may be of particular importance in mediating numerous cellular responses, including control of cell growth, differentiation and adaptation, are the proteins associated with the mitogen-activated protein kinase (MAPK) signalling systems. The MAPKs, in conjunction with the p70 S6k signalling cascade, have emerged as critical components for regulating numerous mechanotransduction-related cellular responses. Here we investigate the ability of uniaxial stretch to activate the MAPK and p70 S6k pathways in adult …

Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough

Eric Blough

The effects of ageing on the cardiovascular system contribute to substantial alterations in cellular morphology and function. The variables regulating these changes are unknown; however, one set of signalling molecules that may be of particular importance in mediating numerous cellular responses, including control of cell growth, differentiation and adaptation, are the proteins associated with the mitogen-activated protein kinase (MAPK) signalling systems. The MAPKs, in conjunction with the p70 S6k signalling cascade, have emerged as critical components for regulating numerous mechanotransduction-related cellular responses. Here we investigate the ability of uniaxial stretch to activate the MAPK and p70 S6k pathways in adult …

Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough

Paulette S. Wehner

The effects of ageing on the cardiovascular system contribute to substantial alterations in cellular morphology and function. The variables regulating these changes are unknown; however, one set of signalling molecules that may be of particular importance in mediating numerous cellular responses, including control of cell growth, differentiation and adaptation, are the proteins associated with the mitogen-activated protein kinase (MAPK) signalling systems. The MAPKs, in conjunction with the p70 S6k signalling cascade, have emerged as critical components for regulating numerous mechanotransduction-related cellular responses. Here we investigate the ability of uniaxial stretch to activate the MAPK and p70 S6k pathways in adult …

Mutant Insulin Degrading Enzyme And Methods Of Use, David W. Rodgers, Louis B. Hersh, Nicholas Noinaj, Eun Suk Song

Molecular and Cellular Biochemistry Faculty Patents

In one aspect, the present invention provides an isolated mutant insulin degrading enzyme (IDE) having an amino acid sequence that is at least 90% identical to SEQ ID NO:1 over its entire length and comprises at least one amino acid substitution at any of amino acid residues 332, 339, 341, 359, 360, 361, 374, 429, 609, 898, 899 or 901 of the sequence. The mutant IDE has a differential activity relative to that of wild-type IDE. Also provided is a polynucleotide encoding the polypeptide of the invention.

The Role Of Oxygen Tension And Insulin-Like Growth Factor Signaling In The Placental Mesenchymal Stem Cell Fate, Amer Youssef

Electronic Thesis and Dissertation Repository

The human placenta of different gestational ages is a readily available source for isolation of adult mesenchymal stem cell (MSC) for potential use in regenerative therapies. The chorionic villous region, the largest component of a placenta that interfaces with the maternal circulation, is a rich source of placental MSCs (PMSCs). To remain multipotent, PMSCs are best maintained in culture conditions that mimic the in vivo microenvironment. Insulin like growth factors (IGFs, IGF-I and -II) and oxygen tension are two of the most important microenvironmental factors in the placenta. They are of low concentration or tension respectively, at early gestation, and …

Detection Of Homocysteine With Bridged Viologen Chemical Probes, Davin Rautiola

Dissertations and Theses

Increased blood plasma concentrations of the aminothiol homocysteine (Hcy) are associated with a variety of disease states including those which cause impaired renal function, many forms of cardiovascular disease, and neurodegenerative diseases such as Alzheimer's. Therefore, Hcy has the potential to be a significant diagnostic biomarker. Routine monitoring of Hcy plasma concentration is encumbered by the time and resources required to quantify Hcy using currently accepted instrumental analysis methods. As part of the continuing effort to develop a quick, reliable, inexpensive, and user-friendly test to quantify Hcy at the point of care, we have designed a series of novel colorimetric …

Unifying The Analysis Of High-Throughput Sequencing Datasets: Characterizing Rna-Seq, 16s Rrna Gene Sequencing And Selective Growth Experiments By Compositional Data Analysis., Andrew D Fernandes, Jennifer Ns Reid, Jean M Macklaim, Thomas A Mcmurrough, David R Edgell, Gregory B Gloor

Biology Publications

BACKGROUND: Experimental designs that take advantage of high-throughput sequencing to generate datasets include RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), sequencing of 16S rRNA gene fragments, metagenomic analysis and selective growth experiments. In each case the underlying data are similar and are composed of counts of sequencing reads mapped to a large number of features in each sample. Despite this underlying similarity, the data analysis methods used for these experimental designs are all different, and do not translate across experiments. Alternative methods have been developed in the physical and geological sciences that treat similar data as compositions. Compositional data analysis …

Altered Mucins (Muc) Trafficking In Benign And Malignant Conditions., Suhasini Joshi, Sushil Kumar, Amit Choudhury, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Mucins are high molecular weight O-glycoproteins that are predominantly expressed at the apical surface of epithelial cells and have wide range of functions. The functional diversity is attributed to their structure that comprises of a peptide chain with unique domains and multiple carbohydrate moieties added during posttranslational modifications. Tumor cells aberrantly overexpress mucins, and thereby promote proliferation, differentiation, motility, invasion and metastasis. Along with their aberrant expression, accumulating evidence suggest the critical role of altered subcellular localization of mucins under pathological conditions due to altered endocytic processes. The mislocalization of mucins and their interactions result in change in the density …

Inhibition Of Rac1 Gtpase Sensitizes Pancreatic Cancer Cells To Γ-Irradiation, Y Yan, Ashley L. Hein, Asserewou Etekpo, Katrina M. Burchett, Chi Lin, Charles A. Enke, Surinder K. Batra, Kenneth Cowan, Michel M. Ouellette

Journal Articles: Biochemistry & Molecular Biology

Radiation therapy is a staple treatment for pancreatic cancer. However, owing to the intrinsic radioresistance of pancreatic cancer cells, radiation therapy often fails to increase survival of pancreatic cancer patients. Radiation impedes cancer cells by inducing DNA damage, which can activate cell cycle checkpoints. Normal cells possess both a G1 and G2 checkpoint. However, cancer cells are often defective in G1 checkpoint due to mutations/alterations in key regulators of this checkpoint. Accordingly, our results show that normal pancreatic ductal cells respond to ionizing radiation (IR) with activation of both checkpoints whereas pancreatic cancer cells respond to IR with G2/M arrest …

"Synthesis Of 4-Aryl-6-Indolylpyridine-3-Carbonitriles And Evaluation Of Their Antiproliferative Activity" Data Files, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Magda Goda El-Meligy, Ahmed Kamel El-Ziaty, Zenat Adeeb Nagib, Keykavous Parang

Pharmacy Faculty Data Sets

No abstract provided.

Benzyl Isothiocyanate As An Adjuvant Chemotherapy Option For Head And Neck Squamous Cell Carcinoma, Mary Allison Wolf

Theses, Dissertations and Capstones

Isothiocyanates (ITCs) are natural phytochemicals produced by cruciferous vegetables. Recent evidence supports that, in addition to cancer prevention, ITCs can use various mechanisms to target malignant cells. Current therapies for cancer often provoke detrimental side effects, however clinical evidence supports that ITCs have little to no side effects in patients. Consequently, ITCs may be a promising treatment option for cancer patients, especially patients suffering from head and neck squamous cell carcinoma (HNSCC).

Despite recent improvements in cancer treatment, overall survival of advanced HNSCC has not improved in the past three decades. Metastasis and chemoresistance represent two detrimental events that greatly …

Science Classics, Mark Masthay

Chemistry Faculty Publications

An essay on the impact of the works in the Imprints and Impressions: Milestones in Human Progress, an exhibition of rare books from the collection of Stuart Rose. Exhibition was held Sept. 29-Nov. 9, 2014, at the University of Dayton.

Novel Roles For Actin In Mitochondrial Fission, Anna L. Hatch, Pinar S. Gurel, Henry N. Higgs

Dartmouth Scholarship

Mitochondrial dynamics, including fusion, fission and translocation, are crucial to cellular homeostasis, with roles in cellular polarity, stress response and apoptosis. Mitochondrial fission has received particular attention, owing to links with several neurodegenerative diseases. A central player in fission is the cytoplasmic dynamin-related GTPase Drp1, which oligomerizes at the fission site and hydrolyzes GTP to drive membrane ingression. Drp1 recruitment to the outer mitochondrial membrane (OMM) is a key regulatory event, which appears to require a pre-constriction step in which the endoplasmic reticulum (ER) and mitochondrion interact extensively, a process termed ERMD (ER-associated mitochondrial division). It is unclear how ER-mitochondrial …

The Effects Of Dihydrobiopterin And Tetrahydrobiopterin On Hydrogen Peroxide And Nitric Oxide Release During Extracorporeal Shockwave Lithotripsy (Eswl), Brittany Deiling

PCOM Biomedical Studies Student Scholarship

ESWL is an effective, non-invasive therapy utilized to fragment stones in the kidney and subsequently be cleared in the urinary tract. Although lithotripsy provides a safer alternative to invasive treatments for removing stones, ESWL may cause vasoconstriction after ESWL treatment, reducing renal blood flow, which can cause kidney damage leading to acute to chronic hypertension clinically. This may be due to kidney vascular endothelial dysfunction, which is characterized as increased oxidative stress and decreased endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) bioavailability. We hypothesized that ESWL would decrease NO and increase hydrogen peroxide (H₂O₂) in …

Single Intrathecal Administration Of The Transcription Factor Decoy Ayx1 Prevents Acute And Chronic Pain After Incisional, Inflammatory, Or Neuropathic Injury, Julien Mamet, Michael Klukinov, Tony L. Yaksh, Shelle A. Malkmus, Samantha Williams, Scott Harris, Donald C. Manning, Bradley K. Taylor, Renee R. Donahue, Frank Porreca, Jennifer Y. Xie, Janice Oyarzo, Timothy J. Brennan, Alberto Subieta, William K. Schmidt, David C. Yeomans

Renee R. Donahue

The persistence of pain after surgery increases the recovery interval from surgery to a normal quality of life. AYX1 is a DNA-decoy drug candidate designed to prevent post-surgical pain following a single intrathecal injection. Tissue injury causes a transient activation of the transcription factor EGR1 in the dorsal root ganglia–dorsal horn network, which then triggers changes in gene expression that induce neuronal hypersensitivity. AYX1 is a potent, specific inhibitor of EGR1 activity that mimics the genomic EGR1- binding sequence. Administered in the peri-operative period, AYX1 dose dependently prevents mechanical hypersensitivity in models of acute incisional (plantar), inflammatory (CFA), and chronic …

Neuroprotective Effects Of Gamma-Glutamylcysteine Ethyl Ester On An In Vivo Moderate Traumatic Brain Injury-Mediated Model And In Vitro In Cortical Astrocytes And Neurons, Jooyoung Cho

Online Theses and Dissertations

Neurodegeneration is the loss of neuronal structures or functions, while neuroprotection is the delay or prevention of neurodegeneration. In traumatic brain injury (TBI), neurodegeneration can occur as the result of oxidative stress, the imbalance of oxidants and antioxidants levels; therefore, antioxidant approaches can be effective therapeutic methods for neuroprotection by attenuating oxidative stress. Glutathione (GSH), a naturally occurring antioxidant, plays an important role in the maintenance of intracellular redox homeostasis by scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this thesis, we attempted to evaluate the abilities of a GSH precursor, gamma-glutamylcysteine ethyl ester (GCEE), to prevent …

American And Brazilian Children With Primary Urolithiasis: Similarities And Disparities., Maria Goretti Moreira Guimarães Penido, Marcelo De Sousa Tavares, Milena Maria Moreira Guimarães, Tarak Srivastava, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Objectives. Considering the differences in location, socioeconomic background, and cultural background, the aim of this study was to try to identify possible factors associated with the increased incidence of urolithiasis by comparing American and Brazilian children with stones.
Methods. Data of 222 American and 190 Brazilian children with urolithiasis were reviewed including age, gender, body mass index, imaging technique used (ultrasound and computed tomography), and 24-hour urine volume and chemistries.
Results. There were no differences between age and gender at diagnosis. Brazilian children were leaner but in no population did obesity rate exceed that of the general population. Ultrasound was …

Facile, Regio-And Diastereoselective Synthesis Of Spiro-Pyrrolidine And Pyrrolizine Derivatives And Evaluation Of Their Antiproliferative Activities, Abdulrahman I. Almansour, Raju Suresh Kumar, Farzana Beevi, Amir Nasrolahi Shirazi, Hasnah Osman, Rusli Ismail, Tan Soo Chen, Brian Sullivan, Kellen Mccaffrey, Alaa Nahhas, Keykavous Parang, Mohamed Ashraf Ali

Pharmacy Faculty Articles and Research

A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene] tetrahydro-4(1H)-pyridinones 2a-n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 M) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-alpha-Phenyl substituted spiro-pyrrolidine derivatives (5a-n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a-n, a number of derivatives including 6a-c and 6i-m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds …

Cyclic Peptide-Capped Gold Nanoparticles For Enhanced Sirna Delivery, Amir Nasrolahi Shirazi, Karissa L. Paquin, Niall G. Howlett, Dindyal Mandal, Keykavous Parang

Pharmacy Faculty Articles and Research

Previously, we have reported the synthesis of a homochiral L-cyclic peptide [WR]5 and its use for delivery of anti-HIV drugs and biomolecules. A physical mixture of HAuCl4 and the peptide generated peptide-capped gold nanoparticles. Here, [WR]5 and [WR]5-AuNPs were tested for their efficiency to deliver a small interfering RNA molecule (siRNA) in human cervix adenocarcinoma (HeLa) cells. Flow cytometry investigation revealed that the intracellular uptake of a fluorescence-labeled non-targeting siRNA (200 nM) was enhanced in the presence of [WR]5 and [WR]5-AuNPs by 2- and 3.8-fold when compared with that of siRNA alone after 24 h incubation. Comparative toxicity results showed …

Synthesis And Evaluation Of Antiproliferative Activity Of Substituted N-(9-Oxo-9h-Xanthen-4-Yl)Benzenesulfonamides, Somayeh Motavallizadeh, Asal Fallah-Tafti, Saeedeh Maleki, Amir Nasrolahi Shirazi, Mahboobeh Pordeli, Maliheh Safavi, Sussan Kabudanian Ardestani, Shaaban Asd, Rakesh Tiwari, Donghoon Oh, Abbas Shafiee, Alireza Foroumadi, Keykavous Parang, Tahmineh Akbarzadeh

Pharmacy Faculty Articles and Research

Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides derivatives were prepared as potential antiproliferative agents. The in vitro antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDAMB- 468) cells. Structure-activity relationship studies revealed …