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2014

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Articles 1 - 30 of 475

Full-Text Articles in Cell and Developmental Biology

Evolutionary Genomics And Adaptive Evolution Of The Hedgehog Gene Family (Shh, Ihh And Dhh) In Vertebrates, Joana Pereira, Warren E. Johnson, Stephen J. O'Brien, Erich D. Jarvis, Guojie Zhang, M. Thomas P. Gilbert, Vitor Vasconcelos, Agostinho Antunes Dec 2014

Evolutionary Genomics And Adaptive Evolution Of The Hedgehog Gene Family (Shh, Ihh And Dhh) In Vertebrates, Joana Pereira, Warren E. Johnson, Stephen J. O'Brien, Erich D. Jarvis, Guojie Zhang, M. Thomas P. Gilbert, Vitor Vasconcelos, Agostinho Antunes

Biology Faculty Articles

The Hedgehog (Hh) gene family codes for a class of secreted proteins composed of two active domains that act as signalling molecules during embryo development, namely for the development of the nervous and skeletal systems and the formation of the testis cord. While only one Hh gene is found typically in invertebrate genomes, most vertebrates species have three (Sonic hedgehog – Shh; Indian hedgehog – Ihh; and Desert hedgehog – Dhh), each with different expression patterns and functions, which likely helped promote the increasing complexity of vertebrates and their successful diversification. In this study, we …


Ontogenetic Scaling Patterns And Functional Anatomy Of The Pelvic Limb Musculature In Emus (Dromaius Novaehollandiae), Luis P. Lamas, Russell P. Main, John R. Hutchinson Dec 2014

Ontogenetic Scaling Patterns And Functional Anatomy Of The Pelvic Limb Musculature In Emus (Dromaius Novaehollandiae), Luis P. Lamas, Russell P. Main, John R. Hutchinson

Department of Basic Medical Sciences Faculty Publications

Emus (Dromaius novaehollandiae) are exclusively terrestrial, bipedal and cursorial ratites with some similar biomechanical characteristics to humans. Their growth rates are impressive, as their body mass increases eighty-fold from hatching to adulthood whilst maintaining the same mode of locomotion throughout life. These ontogenetic characteristics stimulate biomechanical questions about the strategies that allow emus to cope with their rapid growth and locomotion, which can be partly addressed via scaling (allometric) analysis of morphology. In this study we have collected pelvic limb anatomical data (muscle architecture, tendon length, tendon mass and bone lengths) and calculated muscle physiological cross sectional area …


Epigenetic Regulation Of Nuclear Hormone Receptor Dax-1, Michael B. Heskett Dec 2014

Epigenetic Regulation Of Nuclear Hormone Receptor Dax-1, Michael B. Heskett

Master's Theses

DAX-1 (NR0B1) is an orphan nuclear receptor that plays a key role in the development and maintenance of steroidogenic tissue in mammals. Dax-1 is also expressed in mouse embryonic stem (ES) cells and is required to maintain pluripotency. Duplication of the X-chromosome in the region containing the NR0B1 gene results in sex reversal, and mutations in NR0B1 cause adrenal hypoplasia congenita. DAX-1 has been observed to act as a corepressor of other nuclear receptors including androgen receptor (AR), estrogen receptor (ER), and steroidogenic factor 1 (SF-1). In addition to pluripotent ES cells, DAX-1 is primarily expressed in select tissues of …


Subcellular Metabolite And Lipid Analysis Of Xenopus Laevis Eggs By Laesi Mass Spectrometry, Bindesh Shrestha, Prabhakar Sripadi, Brent R. Reschke, Holly D. Henderson, Matthew J. Powell, Sally Ann Moody, Akos Vertes Dec 2014

Subcellular Metabolite And Lipid Analysis Of Xenopus Laevis Eggs By Laesi Mass Spectrometry, Bindesh Shrestha, Prabhakar Sripadi, Brent R. Reschke, Holly D. Henderson, Matthew J. Powell, Sally Ann Moody, Akos Vertes

Anatomy and Regenerative Biology Faculty Publications

Xenopus laevis eggs are used as a biological model system for studying fertilization and early embryonic development in vertebrates. Most methods used for their molecular analysis require elaborate sample preparation including separate protocols for the water soluble and lipid components. In this study, laser ablation electrospray ionization (LAESI), an ambient ionization technique, was used for direct mass spectrometric analysis of X. laevis eggs and early stage embryos up to five cleavage cycles. Single unfertilized and fertilized eggs, their animal and vegetal poles, and embryos through the 32-cell stage were analyzed. Fifty two small metabolite ions, including glutathione, GABA and amino …


Loss Of Thiol Repair Systems In Human Cataractous Lenses, Min Wei, Kui-Yi Xing, Yin-Chuan Fan, Teodosio Libondi, Marjorie F. Lou Dec 2014

Loss Of Thiol Repair Systems In Human Cataractous Lenses, Min Wei, Kui-Yi Xing, Yin-Chuan Fan, Teodosio Libondi, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. The purpose of this study was to investigate the thiol repair systems of thioltransferase (TTase) and thioredoxin (Trx) and oxidation-damaged proteins in human cataractous lenses.

METHODS. Cataractous lenses in humans (57–85 years of age) were classified into cortical, nuclear, mixed, mature, and hypermature cataract types by using a lens opacity classification system, and were obtained by extracapsular cataract extraction (ECCE) procedure. Cortical and nuclear cataracts were grouped by decreasing order of visual acuity into optical chart reading (R), counting fingers (CF), hand motion (HM), and light perception (LP). ECCE lens homogenate was analyzed for glutathione (GSH) level and enzyme …


Role Of Integrin-Linked Kinase In Epidermal Integrity And Barrier Function, Samar Sayedyahossein Dec 2014

Role Of Integrin-Linked Kinase In Epidermal Integrity And Barrier Function, Samar Sayedyahossein

Electronic Thesis and Dissertation Repository

Integrin-linked kinase (ILK) is a β integrin adaptor protein that translates extracellular stimuli to intracellular signaling events. ILK plays a role in actin cytoskeleton dynamics and cell adhesion. The structure and function of the epidermis is highly dependent on cell-cell adhesion and cell-basement membrane interactions. The mechanisms whereby ILK contributes to epidermal integrity are poorly understood. Using a mouse model of epidermis-restricted Ilk gene inactivation, I observed that ILK loss causes abnormal morphology and presence of intra-epidermal and epidermal-dermal microblisters in embryos as early as E17.5. ILK-deficient epidermis is also characterized by abnormal localization or/and absence of adherens junctions, tight …


Dancing Through Life: Allosteric Transitions And Structural Analysis Of Hsp70 And Hsp110 Chaperone Proteins, Gabrielle Stetz, Gennady M. Verkhivker Dec 2014

Dancing Through Life: Allosteric Transitions And Structural Analysis Of Hsp70 And Hsp110 Chaperone Proteins, Gabrielle Stetz, Gennady M. Verkhivker

Student Scholar Symposium Abstracts and Posters

The molecular chaperone protein Hsp70 is centrally involved in cellular homeostasis by assisting in the folding and degradation of protein substrates. Hsp70 is joined by co-chaperones, such as Hsp110, which contribute to specialized tasks of the Hsp70 complex. Imbalances of this heat shock protein system are believed to be involved with the deregulation of cancer pathways and other human diseases. Better understanding of how these heat shock proteins work at the molecular level, which has been investigated using molecular docking tools, will give more clues about biological function. Simulating the formation and function of Hsp70 based chaperone complexes could provide …


Engineered Plga Nanoparticles For Delivery Of Sirna In Mcf-7 Breast Cancer Cells, Sydney Pong, Samit Shah, Vivek Gupta Dec 2014

Engineered Plga Nanoparticles For Delivery Of Sirna In Mcf-7 Breast Cancer Cells, Sydney Pong, Samit Shah, Vivek Gupta

Student Scholar Symposium Abstracts and Posters

Small interfering RNAs have been an emerging medical treatment for molecular based diseases as they are capable of gene-specific knockdown. Appropriate and efficient delivery remains one of the biggest challenges in the development of siRNA as an anti-cancer treatment. Nanoparticles containing siRNA were characterized and the efficacy of various peptides in the transfection of the nanoparticles were tested. A gene silencing assay was developed in order to determine the effect of siRNA therapeutics on gene functionality in breast cancer cells.


Toxicity And Cosmesis Outcomes For Single Fraction Intra-Operative Electron Radiotherapy (Ioert) For Breast Cancer, Monica Hanna, Robert Ash, Wesley Babaran, Michele M. Carpenter, Afshin Forouzannia, Jay K. Harness, Brian Kaltenecker, Snehith Maddula, Venita Williams, Lawrence Wagman Dec 2014

Toxicity And Cosmesis Outcomes For Single Fraction Intra-Operative Electron Radiotherapy (Ioert) For Breast Cancer, Monica Hanna, Robert Ash, Wesley Babaran, Michele M. Carpenter, Afshin Forouzannia, Jay K. Harness, Brian Kaltenecker, Snehith Maddula, Venita Williams, Lawrence Wagman

Student Scholar Symposium Abstracts and Posters

Background: Adjuvant radiation therapy is proven to reduce local recurrence in patients with early stage breast cancer. To reduce toxicity, improve geographic accuracy, and reduce treatment time, IOERT can be utilized as an alternative to external beam radiation therapy. The study’s objective was to determine the short term toxicity and cosmesis profile of single fraction IOERT given as definitive treatment in a community setting. Materials and Methods: From Mar 2012 to Jul 2014, 84 patients (3 bilateral), ages 45-91 y.o. with stage 0-II were treated with IOERT (Mobetron, IntraOp Medical, Sunnyvale, CA). A single 21 Gy fraction was administered to …


Assessment Of The Effects Of Caffeine, Gallic Acid, And Epigallocatechin-3-Gallate On Cell Inhibition, Pim-3 And E. Cadherin Protein Levels In Two Lines Of Pancreatic Cancer Cells, Lena Haddad, Melissa Rowland-Goldsmith Dec 2014

Assessment Of The Effects Of Caffeine, Gallic Acid, And Epigallocatechin-3-Gallate On Cell Inhibition, Pim-3 And E. Cadherin Protein Levels In Two Lines Of Pancreatic Cancer Cells, Lena Haddad, Melissa Rowland-Goldsmith

Student Scholar Symposium Abstracts and Posters

According to the American Cancer Society, pancreatic cancer is currently the fourth leading cause of cancer related deaths in the United States. In addition to being an exceptionally aggressive form of cancer, it is particularly difficult to treat because it is usually diagnosed in late stages after the onset of metastasis (1). Consequently, the current treatments used, including chemotherapy and radiation, have been rendered ineffective (2). As a result, focus has been placed on using dietary alternatives which are known to possess chemopreventive properties (3). Previous studies have indicated that Gallic acid (an important phytochemical in pomegranates) and Epigallocatechin-3-Gallate (the …


Molecular Insights Into Prostate Field Cancerization: Telomere Length, Egr-­‐1 Expression, And Regulation Of Mic-­‐1, Pdgf-­‐A, And Fas, Emily Frisch, Kristin Gabriel, Marco Bisoffi Dec 2014

Molecular Insights Into Prostate Field Cancerization: Telomere Length, Egr-­‐1 Expression, And Regulation Of Mic-­‐1, Pdgf-­‐A, And Fas, Emily Frisch, Kristin Gabriel, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The diagnosis of prostate cancer (adenocarcinoma) relies on screening for elevated prostate-specific antigen (PSA) in blood samples and on digital rectal examination (DRE). With high PSA levels and/or abnormal DRE, physicians recommend a biopsy, which often misses the location of the adenocarcinoma and results in false negatives. Previous studies have shown expression of the key transcription factor early growth response 1 (EGR-1), the pro-survival factor macrophage inhibitor cytokine 1 (MIC-1), and the growth stimulatory platelet derived growth factor A (PDGF-A) to be up-regulated in histologically normal tissues 1 centimeter adjacent to prostate adenocarcinomas. We hypothesize that tumors emerge from “field …


Prostate Field Cancerization -- Thinking Outside The Tumor, Dor Shoshan, Marco Bisoffi Dec 2014

Prostate Field Cancerization -- Thinking Outside The Tumor, Dor Shoshan, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

Prostate field cancerization (or field effect) is characterized by the presence of molecular alterations in histologically normal tissues adjacent to adenocarcinomas. Accordingly, our research indicates deregulated expression of several proteins that define this type of molecular pathology. The scope of the present study was to determine the expression of the key transcription factor and potential marker of field cancerization early growth response 1 (EGR-1) in human prostate tissues derived from prostatectomies and biopsy cores.

EGR-1 was detected by immunofluorescence using a polyclonal anti-human EGR-1 and Alexa Fluor 488-conjugated secondary antibodies. EGR-1 expression was quantitated by determining the pixel count per …


An Activity Aimed At Improving Student Explanations Of Biological Mechanisms, Caleb M. Trujillo, Trevor R. Anderson, Nancy J. Pelaez Dec 2014

An Activity Aimed At Improving Student Explanations Of Biological Mechanisms, Caleb M. Trujillo, Trevor R. Anderson, Nancy J. Pelaez

PIBERG Instructional Innovation Materials

This document is intended for use by instructors and their students. The activity contains steps to introduce students to the MACH model involving analyzing and discussing explanations about biological mechanisms. Initially, students read modified articles about biological mechanisms during class, although instructors may prefer to assign readings outside of class before the activity. During the activity, students are required to analyze the readings for evidence of research methods, analogies, context, and mechanisms. In so doing, students learn how to integrate the information pertaining to each of the MACH model components into a coherent explanation about their biological mechanism. After performing …


A Tetrahedral Version Of The Mach Model For Explaining Biological Mechanisms, Caleb M. Trujillo, Trevor R. Anderson, Nancy J. Pelaez Dec 2014

A Tetrahedral Version Of The Mach Model For Explaining Biological Mechanisms, Caleb M. Trujillo, Trevor R. Anderson, Nancy J. Pelaez

PIBERG Instructional Innovation Materials

This document is intended for both instructors and students. Modified from the original MACH model this version, once cut and folded, creates a tetrahedral model that can conveniently be used as a teaching and learning tool to inform and guide students on how to write expert quality explanations of biological mechanisms. Each vertex of the tetrahedron represents a component of the model namely, Methods, Analogy, Context, and How. For a coherent and complete explanation about molecular mechanisms, it is important to integrate information pertaining to all four components of the model. The tetrahedral MACH model has been tested in both …


Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan Dec 2014

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA …


Arabidopsis Chromatin Remodeler Brahma: Its Functional Interplay With Polycomb Proteins And The Ref6 Histone Demethylase, Chenlong Li Dec 2014

Arabidopsis Chromatin Remodeler Brahma: Its Functional Interplay With Polycomb Proteins And The Ref6 Histone Demethylase, Chenlong Li

Electronic Thesis and Dissertation Repository

BRAHMA (BRM) is a SWI/SNF-type chromatin remodeling ATPase that plays an important role in regulation of gene expression. Tri-methylation of lysine 27 on histone H3 (H3K27me3) is a histone modification that is associated with transcriptionally repressed genes and catalyzed by Polycomb Group (PcG) proteins. BRM has been proposed to antagonize the function of PcG proteins but the underlying molecular mechanism is unclear. To understand how BRM regulates the function of PcG proteins during plant development, a genome-wide analysis of H3K27me3 in brm mutant was performed using chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Loss of BRM leads to increased …


Reverse Genetics Approach To Examine Myosin Xi Functions In Pollen Tube Growth, Stephanie Lin Madison Dec 2014

Reverse Genetics Approach To Examine Myosin Xi Functions In Pollen Tube Growth, Stephanie Lin Madison

Doctoral Dissertations

Pollen tube growth is an essential aspect of plant reproduction because it is the mechanism through which non-motile sperm cells are delivered to ovules thus allowing fertilization to occur. A pollen tube is a single cell that only grows at the tip, and this tip growth depends on actin filaments. Plants encode class VIII and class XI myosins as actin-based motor proteins, of which class XI myosins are required for cell expansion in vegetative tissues.

In Arabidopsis thaliana, 6 of 13 myosin XI genes are expressed in pollen: XIA, XIB, XIC, XID, XIE, and …


The Role Of Nag-1 In Tumorigenesis, Kyung-Won Min Dec 2014

The Role Of Nag-1 In Tumorigenesis, Kyung-Won Min

Doctoral Dissertations

This dissertation explores the nature of a divergent member of the Transforming Growth Factor-β [beta] superfamily, the non-steroidal anti-inflammatory drugs activated gene (NAG-1), as it relates to its regulation and biological activity in cancer context. Our lab has extensively studied on the molecular mechanism by which phytochemicals and NSAIDs induce apoptosis correlation with NAG-1 expression in human colorectal cancer (CRC) cells. Significant data from in vitro studies suggest that NAG-1 has an anti-tumorigenic activity which elicits apoptosis in a cyclooxygenase (COX)-independent manner in CRC cells. Indeed, NAG-1 transgenic mice developed less aberrant polyp foci (APC) compared to those of control …


Understanding The Meiotic Roles Of Sisters Unbound In Drosophila Melanogaster, Badri Krishnan Dec 2014

Understanding The Meiotic Roles Of Sisters Unbound In Drosophila Melanogaster, Badri Krishnan

Doctoral Dissertations

During meiosis, cohesin is required for sister chromatid cohesion and for formation of chromosome cores. Multiple processes including chromosome segregation, recombination and synaptonemal complex (SC) are dependent on cohesin. Cohesin complex consists of two SMC subunits- SMC1, SMC3 and two non-SMC subunits RAD21/REC8 in meiosis and SA. But in Drosophila, non-SMC subunits have not been shown to be required for cohesion. We have identified a gene sisters unbound, which along with previously identified ord and solo, form a group of three genes (sos) which do not have any sequence similarity to cohesins but performs functions …


Novel Posttranslational Modification In Lkb1 Activation And Function, Szu-Wei Lee Dec 2014

Novel Posttranslational Modification In Lkb1 Activation And Function, Szu-Wei Lee

Dissertations & Theses (Open Access)

Cancer cells display dramatic alterations in cellular metabolism to meet their needs of increased growth and proliferation. In the last decade, cancer research has brought these pathways into focus, and one emerging issue that has come to attention is that many oncogenes and tumor-suppressors are intimately linked to metabolic regulation (Jones and Thompson, 2009). One of the key tumor-suppressors involved in metabolism is Liver Kinase B1 (LKB1). LKB1 is the major upstream kinase of the evolutionarily conserved metabolic sensor—AMP-activated protein kinase (AMPK). Activation of the LKB1/AMPK pathway provides a survival advantage for cells under energy stress. LKB1 forms a heterotrimeric …


(R)-Desmolactone Is A Sex Pheromone Or Attractant For The Endangered Valley Elderberry Longhorn Beetle Desmocerus Californicus Dimorphus And Several Congeners (Cerambycidae: Lepturinae), A. M. Ray, R. A. Arnold, I. Swift, P. A. Schapker, S. Mccann, C. J. Marshall, J. S. Mcelfresh, J. G. Millar Dec 2014

(R)-Desmolactone Is A Sex Pheromone Or Attractant For The Endangered Valley Elderberry Longhorn Beetle Desmocerus Californicus Dimorphus And Several Congeners (Cerambycidae: Lepturinae), A. M. Ray, R. A. Arnold, I. Swift, P. A. Schapker, S. Mccann, C. J. Marshall, J. S. Mcelfresh, J. G. Millar

Faculty Scholarship

We report here that (4R,9Z)-hexadec-9-en-4-olide [(R)-desmolactone] is a sex attractant or sex pheromone for multiple species and subspecies in the cerambycid genus Desmocerus. This compound was previously identified as a female-produced sex attractant pheromone of Desmocerus californicus californicus. Headspace volatiles from female Desmocerus aureipennis aureipennis contained (R)-desmolactone, and the antennae of adult males of two species responded strongly to synthetic (R)-desmolactone in coupled gas chromatography-electroantennogram analyses. In field bioassays in California, Oregon, and British Columbia, traps baited with synthetic (R)-desmolactone captured males of several Desmocerus species and subspecies. Only male beetles were captured, indicating that this compound acts as a …


Induction Of Differentiation Of Dental Pulp-Derived Mesenchymal Stem Cells (Dpsc), Aubrey Young Dec 2014

Induction Of Differentiation Of Dental Pulp-Derived Mesenchymal Stem Cells (Dpsc), Aubrey Young

UNLV Theses, Dissertations, Professional Papers, and Capstones

Mesenchymal stem cells are derived from a variety of human tissues and are being bioengineered and studied for possible uses in the advancement of medicine. Recent efforts are being focused on Dental Pulp Stem Cells (DPSC's) due to the accessibility of this tissue. Many factors influence DPSC quality and quantity, including the specific methods used to isolate, collect, concentrate, and store these isolates once they are removed. Ancillary factors, such as the choice of media, the selection of early versus late passage cells, and cryopreservation techniques may also influence the differentiation potential and proliferative capacity of DPSC isolates.

The objective …


Determination Of Expression Levels Of All 20 Dna Polymerases In Zebrafish (Danio Rerio) Thoughout Development And Following Treatment With Mnu, Doxorubicin, And Uv Radiation (Abstract), J. Petovic, L. Sekela, B. Della Fera, L. Ver Steeg, J. Woolcock, M. Miller, Erin E. Gestl Dec 2014

Determination Of Expression Levels Of All 20 Dna Polymerases In Zebrafish (Danio Rerio) Thoughout Development And Following Treatment With Mnu, Doxorubicin, And Uv Radiation (Abstract), J. Petovic, L. Sekela, B. Della Fera, L. Ver Steeg, J. Woolcock, M. Miller, Erin E. Gestl

Biology Student Work

No abstract provided.


Expression Levels Of Dna Damage Response Genes In Zebrafish (Danio Rerio) Following Treatment Methylnitrosourea, Doxorubicin, Or Ultraviolet Light (Abstract), J. Woolcock, H. Khan, K. Joseph, Erin E. Gestl Dec 2014

Expression Levels Of Dna Damage Response Genes In Zebrafish (Danio Rerio) Following Treatment Methylnitrosourea, Doxorubicin, Or Ultraviolet Light (Abstract), J. Woolcock, H. Khan, K. Joseph, Erin E. Gestl

Biology Student Work

No abstract provided.


Characterization Of Histidine Decarboxylase In Drosophila Using An Internal Flag Epitope, Maxwell Mianecki Dec 2014

Characterization Of Histidine Decarboxylase In Drosophila Using An Internal Flag Epitope, Maxwell Mianecki

Masters Theses

Histamine is a neurotransmitter in arthropods and is responsible for synaptic transmission in vision, mechanosensation, temperature sensing and sleep cycle in Drosophila. Histamine is synthesized by the enzyme histidine decarboxylase (HDC). While histamine is detectable within tissues using current immunofluorescent labeling techniques, immunological approaches have not been successful for HDC itself, with both direct antibodies and terminal epitope tags determined to be ineffective. In order to avoid loss of the epitope tag through putative N-­‐ and C-­‐terminal proteolytic cleavage, known to occur for HDC in other organisms, an internal epitope tag that does not disrupt enzyme function was utilized. A …


Jab1 Negatively Regulates Pten And Promotes Resistance To Trastuzumab In Her2-Positive Breast Cancer, Thuy T. Vu Dec 2014

Jab1 Negatively Regulates Pten And Promotes Resistance To Trastuzumab In Her2-Positive Breast Cancer, Thuy T. Vu

Dissertations & Theses (Open Access)

HER2-positive breast cancer, which is characterized by the over-expression of the HER2 onco-protein, accounts for approximately 20% of all breast cancer cases. Trastuzumab (Herceptin), the first targeted therapy approved for HER2-positive disease, potently prevents the activation of signaling pathways downstream of HER2 and significantly improves patients’ outcomes. However, resistance to trastuzumab is inevitable; such resistance can occur through reduced expression of PTEN protein.

Jab1 is over-expressed in 50% of primary cancers and 90% of metastatic tumors. Our lab previously showed that depletion of Jab1 in combination with trastuzumab treatment up-regulated PTEN in mouse xenografts refractory to trastuzumab. PTEN was not …


Glutaredoxin 2 (Grx2) Gene Deletion Induces Early Onset Of Age-Dependent Cataracts In Mice, Hongli Wu, Yibo Yu, Larry David, Ye-Shih Ho, Marjorie . F. Lou Dec 2014

Glutaredoxin 2 (Grx2) Gene Deletion Induces Early Onset Of Age-Dependent Cataracts In Mice, Hongli Wu, Yibo Yu, Larry David, Ye-Shih Ho, Marjorie . F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin 2 (Grx2) is an isozyme of glutaredoxin1 (thioltransferase) present in the mitochondria and nucleus with disulfide reductase and peroxidase activities, and it controls thiol/ disulfide balance in cells. In this study, we investigated whether Grx2 gene deletion could induce faster age-related cataract formation and elucidated the biochemical changes effected by Grx2 gene deletion that may contribute to lens opacity. Slit lamp was used to examine the lenses in Grx2 knock-out (KO) mice and age-matched wild-type (WT) mice ages 1 to 16 months. In the Grx2 null mice, the lens nuclear opacity began at 5 months, 3 months sooner than …


Mdm2-Mediated Degradation Of Sirt6 Phosphorylated By Akt1 Promotes Tumorigenesis And Trastuzumab Resistance In Breast Cancer, Umadevi Thirumurthi Dec 2014

Mdm2-Mediated Degradation Of Sirt6 Phosphorylated By Akt1 Promotes Tumorigenesis And Trastuzumab Resistance In Breast Cancer, Umadevi Thirumurthi

Dissertations & Theses (Open Access)

Sirtuin6 (SIRT6) is one of the members of the Sirtuin family and functions as a longevity assurance gene by promoting genomic stability. It also regulates various cancer-associated pathways and was recently established as a bonafide tumor suppressor in colon cancer. This suggests that SIRT6 is an attractive target for pharmacological activation in cancer treatment, and hence, identification of potential regulators of SIRT6 would be an important and critical contribution towards cancer treatment. Here, we show that AKT1 phosphorylates SIRT6 at Ser338 and induces MDM2-SIRT6 interaction, priming SIRT6 for degradation via the MDM2-dependent ubiquitin-proteasome pathway. Blocking SIRT6 Ser338 phosphorylation …


Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes Dec 2014

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes

Dissertations & Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear …


Extent Of Cysteine Modification Of Snap-25 In Vitro, Alex Mcgregor Dabell Dec 2014

Extent Of Cysteine Modification Of Snap-25 In Vitro, Alex Mcgregor Dabell

Theses and Dissertations

Exocytosis, the fusion of a vesicle to a cellular membrane, involves a protein named SNAP-25. This protein, containing two alpha helices connected with a linker region, is localized to the cell membrane via palmitic acids attached to the cysteine residues of its linker region in a process called palmitoylation. Are cysteine residues of the SNAP-25 linker region palmitoylated in an ordered manner and to a particular extent? The answer to this question may give insight into the regulated nature of exocytosis. While it is generally accepted that SNAP-25 must be palmitoylated in order to perform its exocytotic functions, the details …