Cell and Developmental Biology Commons^™

Higher Il-6 And Il6:Igf Ratio In Patients With Barth Syndrome, Lori D. Wilson, Sadeeka Al-Majid, Cyril Rakovski, Christina D. Schwindt

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background: Barth Syndrome (BTHS) is a serious X-linked genetic disorder associated with mutations in the tafazzin gene (TAZ, also called G4.5). The multi-system disorder is primarily characterized by the following pathologies: cardiac and skeletal myopathies, neutropenia, growth delay, and exercise intolerance. Although growth anomalies have been widely reported in BTHS, there is a paucity of research on the role of inflammation and the potential link to alterations in growth factors levels in BTHS patients.

Methods: Plasma from 36 subjects, 22 patients with Barth Syndrome (0.5 - 24 yrs) and 14 healthy control males (8 - 21 yrs) was …

Simulating Molecular Mechanisms Of The Mdm2-Mediated Regulatory Interactions: A Conformational Selection Model Of The Mdm2 Lid Dynamics, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Diversity and complexity of MDM2 mechanisms govern its principal function as the cellular antagonist of the p53 tumor suppressor. Structural and biophysical studies have demonstrated that MDM2 binding could be regulated by the dynamics of a pseudo-substrate lid motif. However, these experiments and subsequent computational studies have produced conflicting mechanistic models of MDM2 function and dynamics. We propose a unifying conformational selection model that can reconcile experimental findings and reveal a fundamental role of the lid as a dynamic regulator of MDM2-mediated binding. In this work, structure, dynamics and energetics of apo-MDM2 are studied as a function of posttranslational modifications …

Inefficient Replication Reduces Reca-Mediated Repair Of Uvdamaged Plasmids Introduced Into Competent Escherichia Coli, Harout Arthur Jeiranian, Charmain T. Courcelle, Justin Courcelle

Biology Faculty Publications and Presentations

Transformation of Escherichia coli with purified plasmids containing DNA damage is frequently used as a tool to characterize repair pathways that operate on chromosomes. In this study, we used an assay that allowed us to quantify plasmid survival and to compare how efficiently various repair pathways operate on plasmid DNA introduced into cells relative to their efficiency on chromosomal DNA. We observed distinct differences between the mechanisms operating on the transforming plasmid DNA and the chromosome. An average of one UV-induced lesion was sufficient to inactivate ColE1-based plasmids introduced into nucleotide excision repair mutants, suggesting an essential role for repair …

Uvrd Participation In Nucleotide Excision Repair Is Required For The Recovery Of Dna Synthesis Following Uv-Induced Damage In Escherichia Coli, Kelley Nicole Newton, Charmain T. Courcelle, Justin Courcelle

Biology Faculty Publications and Presentations

UvrD is a DNA helicase that participates in nucleotide excision repair and several replication-associated processes, including methyl-directed mismatch repair and recombination. UvrD is capable of displacing oligonucleotides from synthetic forked DNA structures in vitro and is essential for viability in the absence of Rep, a helicase associated with processing replication forks. These observations have led others to propose that UvrD may promote fork regression and facilitate resetting of the replication fork following arrest. However, the molecular activity of UvrD at replication forks in vivo has not been directly examined. In this study, we characterized the role UvrD has in processing …

Comparative Developmental Transcriptomics Of Echinoderms, Roy Vaughn

USF Tampa Graduate Theses and Dissertations

The gastrula stage represents the point in development at which the three primary germ layers diverge. At this point the gene regulatory networks that specify the germ layers are established and the genes that define the differentiated states of the tissues have begun to be activated. These networks have been well characterized in sea urchins, but not in other echinoderms. Embryos of the brittle star Ophiocoma wendtii share a number of developmental features with sea urchin embryos, including the ingression of mesenchyme cells that give rise to an embryonic skeleton. Notable differences are that no micromeres are formed during cleavage …

Lenalidomide Targets The T-Cell Co-Stimulatory Pathway To Mediate Immune Modulation, Jessica Marie Mcdaniel

USF Tampa Graduate Theses and Dissertations

T-cells are lymphocytes that make up part of the adaptive arm of the immune system, and are essential for efficient protection from and eradication of viruses and pathogens. T-cells not only play an important role in protection from external agents, but also regulate and prevent activation towards self-peptides and detect and remove erratically growing cells. Alterations in T-cell activation and suppression contribute to auto-immunity, immunocompromised disorders, and cancer progression.

The immune system, and T-cells in particular, provides daily surveillance, recognition and destruction of aberrant cells. Although the immune system is proficient at suppressing malignant progression, tumor cells acquire various methods …

Cytoplasmic Sequestration Of The Tumor Suppressor P53 By A Heat Shock Protein 70 Family Member, Mortalin, In Human Colorectal Adenocarcinoma Cell Lines, Erin E. Gestl, S. Anne Boettger

Biology Faculty Publications

No abstract provided.

Novel Report Of Expression And Function Of Cd97 In Malignant Gliomas: Correlation With Wilms Tumor 1 Expression And Glioma Cell Invasiveness Laboratory Investigation, Archana Chidambaram, Helen L. Fillmore, Timothy E. Van Meter, Catherine I. Dumur, William C. Broaddus

Office of Research Faculty & Staff Publications

Object. The Wilms tumor 1 (WT1) protein—a developmentally regulated transcription factor—is aberrantly expressed in gliomas and promotes their malignant phenotype. However, little is known about the molecular allies that help it mediate its oncogenic functions in glioma cells.

Methods. The authors used short interfering RNA (siRNA) to suppress WT1 expression in glioblastoma (GBM) cells and evaluated the effect of this on GBM cell invasiveness. Gene expression analysis was then used to identify the candidate genes that were altered as a result of WT1 silencing. One candidate target, CD97, was then selected for further investigation into its role by suppressing …

The Role Of Nucleotide Excision Repair In Restoring Replication Following Uv-Induced Damage In Escherichia Coli, Kelley Nicole Newton

Dissertations and Theses

Following low levels of UV exposure, Escherichia coli cells deficient in nucleotide excision repair recover and synthesize DNA at near wild type levels, an observation that formed the basis of the post replication recombination repair model. In this study, we characterized the DNA synthesis that occurs following UV-irradiation in the absence of nucleotide excision repair and show that although this synthesis resumes at near wild type levels, it is coincident with a high degree of cell death. We confirm that the replication occurring under these conditions involves extensive levels of strand exchange. However, cells undergoing this form of replication accumulate …

The Effects Of Hypoxia And Temperature On Developing Embryos Of The Annual Killifish Austrofundulus Limnaeus, Skye N. Anderson

Dissertations and Theses

Little is known about the physiology or biochemistry of hypoxia (reduced levels of oxygen) tolerance during development in vertebrate embryos. In most species, relatively brief bouts of severe hypoxia are lethal or teratogenic. An exception to such hypoxia intolerance is the annual killifish Austrofundulus limnaeus, in which populations persist in hypoxic environments. This species inhabits seasonal ponds in Venezuela, surviving through the dry season in the form of diapausing embryos. Embedded in the pond sediment, embryos of A. limnaeus are routinely exposed to hypoxia and anoxia (lack of oxygen) as part of their normal development. Here, we exposed embryos to …

Acth: The Uninhibitable (Or Is It)?, Anthony Baglio, Jonathan Forsberg, Daniel Mcfarlane, Justin Nichols, Heather G. Kuruvilla

Science and Mathematics Faculty Presentations

Adrenal corticotropic hormone, or ACTH, is a peptide hormone secreted by the anterior pituitary gland. The full-length peptide is 39 amino acids long. ACTH signals through a G-protein linked receptor in humans, using the adenylyl cyclase pathway. Potassium and chloride channels have also been implicated in human ACTH signaling.

Tetrahymena thermophila are free-living, ciliated ptotozoans. These organisms exhibit avoidance behavior toward many polycationic peptides, which serve as chemorepellents. The reason for this is unknown; however, it is hypothesized that natural predators of T. thermophila secrete polycationic peptides, and that polycation avoidance allows T. thermophila to escape predation. We obtained a …

Amino Acid Residues In The Non-Structural Protein 1 Of Porcine Reproductive And Respiratory Syndrome Virus Involved In Down-Regulation Of Tnf-Cx Expression In Vitro And Attenuation In Vivo, Sakthivel Subramaniam, Lalit Beura, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses tumor necrosis factor-alpha (TNF-α) production at both transcriptional and post-transcriptional levels by its non-structural proteins 1α and 1β (Nsp1α and Nsp1β). To identifY the amino acid residues responsible for this activity, we generated several alanine substitution mutants of Nsp1α and Nsp1β. Examination of the mutant proteins revealed that Nsp1α residues Gly90, Asn91 , Arg97, Argl 00 and Arg124 were necessary for TNF-α promoter suppression, whereas several amino acids spanning the entire Nsp1β ~ were found to be required for this activity. Two mutant viruses, with mutations at Nsp1α Gly90 or Nsp1β residues …

Antibody Responses To Lytic And Latent Human Herpesvirus 8 Antigens Among Hiv-Infected Patients In Central China, Tiejun Zhang, Na He, Yingying Ding, Qingwu Jiang, Charles Wood

Nebraska Center for Virology: Faculty Publications

Human herpesvirus 8 (HHV8) is an important opportunistic infection of HIV/AIDS. However, very little is known about antibody seropositivities to HHV8 lytic and latent antigens among HIVinfected patients in China. Therefore, a cross-sectional study was conducted to explore HHV8 serostatus among 316 HIV-infected patients in a rural area of central China. The antibody seropositivity to HHV8 ORF65 (lytic) and LANA (latent) antigens was 12.7% and 10.4%, respectively. Patients who were naïve to antiretroviral therapy (ART) were more likely to be seropositive for antibodies to ORF65 (OR: 3.79; 95% CI: 1.71–8.42) and LANA (OR: 3.77; 95% CI: 1.55–9.14) than patients receiving …

Triticum Mosaic Poacevirus Enlists P1 Rather Than Hc-Pro To Suppress Rna Silencing-Mediated Host Defense, Satyanarayana Tatineni, Feng Qu, Ruhui Li, Thomas Jack Morris, Roy French

Nebraska Center for Virology: Faculty Publications

Triticum mosaic virus (TriMV) is the type species of the newly established Poacevirus genus in the family Potyviridae. In this study, we demonstrate that in contrast to the helper component- proteinase (HC-Pro) of Potyvirus species, the P1 proteins of TriMV and Sugarcane steak mosaic poacevirus function in suppression of RNA silencing (SRS). TriMV P1 effectively suppressed silencing induced by single- or double-stranded RNAs (ss/ds RNAs), and disrupted the systemic spread of silencing signals at a step after silencing signal production. Interestingly, contrary to enhanced SRS activity of potyviral HC-Pro by co-expression with P1, the presence of TriMV HC-Pro reduced …

Chloroviruses: Not Your Everyday Plant Virus, James L. Van Etten, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Viruses infecting higher plants are among the smallest viruses known and typically have four to ten protein-encoding genes. By contrast, many viruses that infect algae (classified in the virus family Phycodnaviridae) are among the largest viruses found to date and have up to 600 protein- encoding genes. This brief review focuses on one group of plaque-forming phycodnaviruses that infect unicellular chlorella-like green algae. The prototype chlorovirus PBCV-1 has more than 400 protein-encoding genes and 11 tRNA genes. About 40% of the PBCV-1 encoded proteins resemble proteins of known function including many that are completely unexpected for a virus. In many …

Subunit Organization Of The Membrane-Bound Hiv-1 Envelope Glycoprotein Trimer, Youdong Mao, Liping Wang, Christopher Gu, Alon Herschhorn, Shi-Hua Xiang, Hillel Haim, Xinzhen Yang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike is a molecular machine that mediates virus entry into host cells and is the sole target for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric gp160 precursor into three gp120 and three gp41 subunits. Here we describe an ~11-Å cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and three gp41 subunits form a cage-like structure with an interior void surrounding the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane region, the torus-like gp41 ectodomain, and …

Leptin Promotes Glioblastoma , Johnathan Lawrence, Nicholas J. Cook, Richard A. Rovin, Robert J. Winn

Journal Articles

The hormone leptin has a variety of functions. Originally known for its role in satiety and weight loss, leptin more recently has been shown to augment tumor growth in a variety of cancers. Within gliomas, there is a correlation between tumor grade and tumor expression of leptin and its receptor. This suggests that autocrine signaling within the tumor microenvironment may promote the growth of high-grade gliomas. Leptin does this through stimulation of cellular pathways that are also advantageous for tumor growth and recurrence: antiapoptosis, proliferation, angiogenesis, and migration. Conversely, a loss of leptin expression attenuates tumor growth. In animal models …

Toward A Functional Characterization Of The Acidic-Domain Of The Chloroplast Protein Import Receptor Toc159, Joseph K. Weston

Theses and Dissertations (Comprehensive)

Chloroplasts are members of a diverse class of organelles called plastids that differentiate plants from other eukaryotes, and are the site of a number of essential biochemical pathways including photosynthesis. Nuclear-encoded pre-proteins, which account for ~95% of chloroplast proteins, are post-translationally imported into plastids across the double envelope membrane. In the model plant Arabidopsis thaliana, the majority of pre-proteins are imported via the Toc (translocon at outer envelope membrane of chloroplasts) and Tic (translocon at inner envelope membrane of chloroplasts) complexes, the key components of which have been identified. The Toc159 …

Cutaneous Papilloma And Squamous Cell Carcinoma Therapy Utilizing Nanosecond Pulsed Electric Fields (Nspef), Dong Yin, Wangrong G. Yang, Jack Weissberg, Catherine B. Goff, Weikai Chen, Yoshio Kuwayama, Amanda Leiter, Hongtao Xing, Antonie Meixel, Daria Gaut, Fikret Kirkbir, David Sawcer, P. Thomas Vernier, Jonathan W. Said, Martin A. Gundersen, H. Phillip Koeffler

Bioelectrics Publications

Nanosecond pulsed electric fields (nsPEF) induce apoptotic pathways in human cancer cells. The potential therapeutic effective of nsPEF has been reported in cell lines and in xenograft animal tumor model. The present study investigated the ability of nsPEF to cause cancer cell death in vivo using carcinogen-induced animal tumor model, and the pulse duration of nsPEF was only 7 and 14 nano second (ns). An nsPEF generator as a prototype medical device was used in our studies, which is capable of delivering 7-30 nanosecond pulses at various programmable amplitudes and frequencies. Seven cutaneous squamous cell carcinoma cell lines and five …

Decorin Expression, Straw-Like Structure, And Differentiation Of Human Costal Cartilage, Michael W. Stacey, Janna Grubb, Anthony Asmar, Julie Pryor, Hani Elsayed-Ali, Ali Beskok, Diganta Dutta, Annie Fecteau, Alice Werner, Dennis A. Darby, Robert Kelly

Bioelectrics Publications

Costal cartilage is much understudied compared with the load-bearing cartilages. Abnormally grown costal cartilages are associated with the inherited chest wall deformities pectus excavatum and pectus carinatum resulting in sunken and pigeon chests, respectively. A lack of understanding of the ultrastructural and molecular biology of costal cartilage is a major confounder in predicting causes and outcomes of these disorders. This study analyzed the structure of marginal human costal cartilage (ribs 6-10) through scanning electron and atomic force microscopes and identified the presence of straw-like structures running longitudinally. We also demonstrated that chondrocytes tend to occur singly or as doublets and …