Digital Commons Network^™

Predictive Oncology: A Review Of Multidisciplinary, Multiscale In Silico Modeling Linking Phenotype, Morphology And Growth, Sandeep Sanga, Hermann B. Frieboes, Xiaoming Zheng, Robert Gatenby, Elaine L. Bearer, Vittorio Cristini

Faculty, Staff and Student Publications

Empirical evidence and theoretical studies suggest that the phenotype, i.e., cellular- and molecular-scale dynamics, including proliferation rate and adhesiveness due to microenvironmental factors and gene expression that govern tumor growth and invasiveness, also determine gross tumor-scale morphology. It has been difficult to quantify the relative effect of these links on disease progression and prognosis using conventional clinical and experimental methods and observables. As a result, successful individualized treatment of highly malignant and invasive cancers, such as glioblastoma, via surgical resection and chemotherapy cannot be offered and outcomes are generally poor. What is needed is a deterministic, quantifiable method to enable …

Computer Simulation Of Glioma Growth And Morphology, Hermann B. Frieboes, John S Lowengrub, S Wise, X Zheng, Paul Macklin, Elaine L. Bearer, Vittorio Cristini

Faculty, Staff and Student Publications

Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques …

All In The Family: Atypical Hsp70 Chaperones Are Conserved Modulators Of Hsp70 Activity, Lance Shaner, Kevin A Morano

Faculty, Staff and Student Publications

Divergent relatives of the Hsp70 protein chaperone such as the Hsp110 and Grp170 families have been recognized for some time, yet their biochemical roles remained elusive. Recent work has revealed that these "atypical" Hsp70s exist in stable complexes with classic Hsp70s where they exert a powerful nucleotide-exchange activity that synergizes with Hsp40/DnaJ-type cochaperones to dramatically accelerate Hsp70 nucleotide cycling. This represents a novel evolutionary transition from an independent protein-folding chaperone to what appears to be a dedicated cochaperone. Contributions of the atypical Hsp70s to established cellular roles for Hsp70 now must be deciphered.

Characterization Of Hsp70 Binding And Nucleotide Exchange By The Yeast Hsp110 Chaperone Sse1, Lance Shaner, Rui Sousa, Kevin A Morano

Faculty, Staff and Student Publications

SSE1 and SSE2 encode the essential yeast members of the Hsp70-related Hsp110 molecular chaperone family. Both mammalian Hsp110 and the Sse proteins functionally interact with cognate cytosolic Hsp70s as nucleotide exchange factors. We demonstrate here that Sse1 forms high-affinity (Kd approximately 10-8 M) heterodimeric complexes with both yeast Ssa and mammalian Hsp70 chaperones and that binding of ATP to Sse1 is required for binding to Hsp70s. Sse1.Hsp70 heterodimerization confers resistance to exogenously added protease, indicative of conformational changes in Sse1 resulting in a more compact structure. The nucleotide binding domains of both Sse1/2 and the Hsp70s dictate interaction specificity and …

Role Of The Cytoplasmic Domain In Anabaena Sensory Rhodopsin Photocycling: Vectoriality Of Schiff Base Deprotonation, Oleg A Sineshchekov, Elena N Spudich, Vishwa D Trivedi, John L Spudich

Faculty, Staff and Student Publications

Light-induced electric signals in intact E. coli cells generated by heterologously expressed full-length and C-terminally truncated versions of Anabaena sensory rhodopsin (ASR) demonstrate that the charge movements within the membrane-embedded part of the molecule are stringently controlled by the cytoplasmic domain. In particular, truncation inverts the direction of proton movement during Schiff base deprotonation from outward to cytoplasmic. Truncation also alters faster charge movements that occur before Schiff base deprotonation. Asp(217) as previously shown by FTIR serves as a proton acceptor in the truncated ASR but not in the full-length version, and its mutation to Asn restores the natural outward …

Library Holiday Hours, Vol.4 (6) November - December 2006, Houston Academy Of Medicine-Texas Medical Center Library

The Insider (2003-2008)

No abstract provided.

Proteomic Identification Of In Vivo Substrates For Matrix Metalloproteinases 2 And 9 Reveals A Mechanism For Resolution Of Inflammation, Kendra J Greenlee, David B Corry, David A Engler, Risë K Matsunami, Philippe Tessier, Richard G Cook, Zena Werb, Farrah Kheradmand

Faculty, Staff and Student Publications

Clearance of allergic inflammatory cells from the lung through matrix metalloproteinases (MMPs) is necessary to prevent lethal asphyxiation, but mechanistic insight into this essential homeostatic process is lacking. In this study, we have used a proteomics approach to determine how MMPs promote egression of lung inflammatory cells through the airway. MMP2- and MMP9-dependent cleavage of individual Th2 chemokines modulated their chemotactic activity; however, the net effect of complementing bronchoalveolar lavage fluid of allergen-challenged MMP2(-/-)/MMP9(-/-) mice with active MMP2 and MMP9 was to markedly enhance its overall chemotactic activity. In the bronchoalveolar fluid of MMP2(-/-)/MMP9(-/-) allergic mice, we identified several chemotactic …

Insights Into Transcription Enhancer Factor 1 (Tef-1) Activity From The Solution Structure Of The Tea Domain, Asokan Anbanandam, Diana C Albarado, Catherine T Nguyen, Georg Halder, Xiaolian Gao, Sudha Veeraraghavan

Faculty, Staff and Student Publications

Transcription enhancer factor 1 is essential for cardiac, skeletal, and smooth muscle development and uses its N-terminal TEA domain (TEAD) to bind M-CAT elements. Here, we present the first structure of TEAD and show that it is a three-helix bundle with a homeodomain fold. Structural data reveal how TEAD binds DNA. Using structure-function correlations, we find that the L1 loop is essential for cooperative loading of TEAD molecules on to tandemly duplicated M-CAT sites. Furthermore, using a microarray chip-based assay, we establish that known binding sites of the full-length protein are only a subset of DNA elements recognized by TEAD. …

Three Strategically Placed Hydrogen-Bonding Residues Convert A Proton Pump Into A Sensory Receptor, Yuki Sudo, John L Spudich

Faculty, Staff and Student Publications

In haloarchaea, light-driven ion transporters have been modified by evolution to produce sensory receptors that relay light signals to transducer proteins controlling motility behavior. The proton pump bacteriorhodopsin and the phototaxis receptor sensory rhodopsin II (SRII) differ by 74% of their residues, with nearly all conserved residues within the photoreactive retinal-binding pocket in the membrane-embedded center of the proteins. Here, we show that three residues in bacteriorhodopsin replaced by the corresponding residues in SRII enable bacteriorhodopsin to efficiently relay the retinal photoisomerization signal to the SRII integral membrane transducer (HtrII) and induce robust phototaxis responses. A single replacement (Ala-215-Thr), bridging …

Evolution Of Sensory Complexity Recorded In A Myxobacterial Genome, B S Goldman, W C Nierman, D Kaiser, S C Slater, A S Durkin, J A Eisen, J Eisen, C M Ronning, W B Barbazuk, M Blanchard, C Field, C Halling, G Hinkle, O Iartchuk, H S Kim, C Mackenzie, R Madupu, N Miller, A Shvartsbeyn, S A Sullivan, M Vaudin, R Wiegand, H B Kaplan

Faculty, Staff and Student Publications

Myxobacteria are single-celled, but social, eubacterial predators. Upon starvation they build multicellular fruiting bodies using a developmental program that progressively changes the pattern of cell movement and the repertoire of genes expressed. Development terminates with spore differentiation and is coordinated by both diffusible and cell-bound signals. The growth and development of Myxococcus xanthus is regulated by the integration of multiple signals from outside the cells with physiological signals from within. A collection of M. xanthus cells behaves, in many respects, like a multicellular organism. For these reasons M. xanthus offers unparalleled access to a regulatory network that controls development and …

Endocarditis And Biofilm-Associated Pili Of Enterococcus Faecalis, Sreedhar R Nallapareddy, Kavindra V Singh, Jouko Sillanpää, Danielle A Garsin, Magnus Höök, Stanley L Erlandsen, Barbara E Murray

Faculty, Staff and Student Publications

Increasing multidrug resistance in Enterococcus faecalis, a nosocomial opportunist and common cause of bacterial endocarditis, emphasizes the need for alternative therapeutic approaches such as immunotherapy or immunoprophylaxis. In an earlier study, we demonstrated the presence of antibodies in E. faecalis endocarditis patient sera to recombinant forms of 9 E. faecalis cell wall-anchored proteins; of these, we have now characterized an in vivo-expressed locus of 3 genes and an associated sortase gene (encoding sortase C; SrtC). Here, using mutation analyses and complementation, we demonstrated that both the ebp (encoding endocarditis and biofilm-associated pili) operon and srtC are important for biofilm production …

Time To Renal Disease And End-Stage Renal Disease In Profile: A Multiethnic Lupus Cohort, Graciela S. Alarcón, Gerald Mcgwin, Michelle Petri, Rosalind Ramsey-Goldman, Barri J. Fessler, Luis M. Vilá, Jeffrey C. Edberg, John D. Reveille, Robert P. Kimberly

Faculty, Staff and Student Publications

BACKGROUND: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE).

METHODS AND FINDINGS: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic-demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of …

Minimizing Radiation Injury And Neoplastic Effects During Pediatric Fluoroscopy: What Should We Know?, Louis Kenneth Wagner

Faculty, Staff and Student Publications

Radiation-induced injuries from fluoroscopic procedures in pediatric patients have occurred, and young patients are at greatest risk of many radiation-induced neoplasms. Some fluoroscopists have been injured from their use of fluoroscopy, and they are known to be at risk of radiation-induced neoplasm when radiation is not well-controlled. This article reviews the circumstances that lead to radiation injury and delineates some procedural methods to avoid injury and limit radiation exposure to both the patient and the fluoroscopist.

Platelet-Activating Factor Is Crucial In Psoralen And Ultraviolet A-Induced Immune Suppression, Inflammation, And Apoptosis, Peter Wolf, Dat X Nghiem, Jeffrey P Walterscheid, Scott Byrne, Yumi Matsumura, Yasuhiro Matsumura, Cora Bucana, Honnavara N Ananthaswamy, Stephen E Ullrich

Faculty, Staff and Student Publications

Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF …

Ligand-Signaled Upregulation Of Enterococcus Faecalis Ace Transcription, A Mechanism For Modulating Host-E Faecalis Interaction, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecalis, the third most frequent cause of bacterial endocarditis, appears to be equipped with diverse surface-associated proteins showing structural-fold similarity to the immunoglobulin-fold family of staphylococcal adhesins. Among the putative E. faecalis surface proteins, the previously characterized adhesin Ace, which shows specific binding to collagen and laminin, was detectable in surface protein preparations only after growth at 46 degrees C, mirroring the finding that adherence was observed in 46 degrees C, but not 37 degrees C, grown E. faecalis cultures. To elucidate the influence of different growth and host parameters on ace expression, we investigated ace expression using E. …

Nanoparticle Agglomerates For Pulmonary Drug Delivery, Rohan Bhavane

Dissertations and Theses (Open Access)

The Pulmonary route has been traditionally used to treat diseases of the respiratory tract. However, important research within the last two decades have shown that in addition to treating local diseases, a wide range of systemic diseases can be treated by delivering drugs to the lungs. The recent FDA approval to market Exubera, an inhalable form of insulin developed by Pfizer, to treat Diabetes, may just be the stepping stone that the pharmaceutical industry needs to market other drugs to treat systemic diseases via the lungs. However, this technology still needs repeated drug doses to control glucose levels, as the …

Role Of A2b Adenosine Receptor Signaling In Adenosine-Dependent Pulmonary Inflammation And Injury, Chun-Xiao Sun, Hongyan Zhong, Amir Mohsenin, Eva Morschl, Janci L Chunn, Jose G Molina, Luiz Belardinelli, Dewan Zeng, Michael R Blackburn

Faculty, Staff and Student Publications

Adenosine has been implicated in the pathogenesis of chronic lung diseases such as asthma and chronic obstructive pulmonary disease. In vitro studies suggest that activation of the A2B adenosine receptor (A2BAR) results in proinflammatory and profibrotic effects relevant to the progression of lung diseases; however, in vivo data supporting these observations are lacking. Adenosine deaminase-deficient (ADA-deficient) mice develop pulmonary inflammation and injury that are dependent on increased lung adenosine levels. To investigate the role of the A2BAR in vivo, ADA-deficient mice were treated with the selective A2BAR antagonist CVT-6883, and pulmonary inflammation, fibrosis, and airspace integrity were assessed. Untreated and …

Natriuretic Peptides And Nitric Oxide Stimulate Cgmp Synthesis In Different Cellular Compartments, Leslie A Piggott, Kathryn A Hassell, Zuzana Berkova, Andrew P Morris, Michael Silberbach, Thomas C Rich

Faculty, Staff and Student Publications

Cyclic nucleotide-gated (CNG) channels are a family of ion channels activated by the binding of cyclic nucleotides. Endogenous channels have been used to measure cyclic nucleotide signals in photoreceptor outer segments and olfactory cilia for decades. Here we have investigated the subcellular localization of cGMP signals by monitoring CNG channel activity in response to agonists that activate either particulate or soluble guanylyl cyclase. CNG channels were heterologously expressed in either human embryonic kidney (HEK)-293 cells that stably overexpress a particulate guanylyl cyclase (HEK-NPRA cells), or cultured vascular smooth muscle cells (VSMCs). Atrial natriuretic peptide (ANP) was used to activate the …

The Interaction Between Internal And External Information On Relational Data Search, Yang Gong

Dissertations and Theses (Open Access)

People often use tools to search for information. In order to improve the quality of an information search, it is important to understand how internal information, which is stored in user’s mind, and external information, represented by the interface of tools interact with each other. How information is distributed between internal and external representations significantly affects information search performance. However, few studies have examined the relationship between types of interface and types of search task in the context of information search. For a distributed information search task, how data are distributed, represented, and formatted significantly affects the user search performance …

Transcriptional Regulation Of The Borrelia Burgdorferi Antigenically Variable Vlse Surface Protein, Tomasz Bykowski, Kelly Babb, Kate Von Lackum, Sean P Riley, Steven J Norris, Brian Stevenson

Faculty, Staff and Student Publications

The Lyme disease agent Borrelia burgdorferi can persistently infect humans and other animals despite host active immune responses. This is facilitated, in part, by the vls locus, a complex system consisting of the vlsE expression site and an adjacent set of 11 to 15 silent vls cassettes. Segments of nonexpressed cassettes recombine with the vlsE region during infection of mammalian hosts, resulting in combinatorial antigenic variation of the VlsE outer surface protein. We now demonstrate that synthesis of VlsE is regulated during the natural mammal-tick infectious cycle, being activated in mammals but repressed during tick colonization. Examination of cultured B. …

Mutations Affecting Beta-Tubulin Folding And Degradation, Yaqing Wang, Guoling Tian, Nicholas J Cowan, Fernando Cabral

Faculty, Staff and Student Publications

Revertants of a colcemid-resistant Chinese hamster ovary cell line with an altered (D45Y) beta-tubulin have allowed the identification of four cis-acting mutations (L187R, Y398C, a 12-amino acid in-frame deletion, and a C-terminal truncation) that act by destabilizing the mutant tubulin and preventing it from incorporating into microtubules. These unstable beta-tubulins fail to form heterodimers and are predominantly found in association with the chaperonin CCT, suggesting that they cannot undergo productive folding. In agreement with these in vivo observations, we show that the defective beta-tubulins do not stably interact with cofactors involved in the tubulin folding pathway and, hence, fail to …

Understanding Interruptions In Healthcare: Developing A Model, Juliana J. Brixey

Dissertations and Theses (Open Access)

Developing a Model Interruption is a known human factor that contributes to errors and catastrophic events in healthcare as well as other high-risk industries. The landmark Institute of Medicine (IOM) report, To Err is Human, brought attention to the significance of preventable errors in medicine and suggested that interruptions could be a contributing factor. Previous studies of interruptions in healthcare did not offer a conceptual model by which to study interruptions. As a result of the serious consequences of interruptions investigated in other high-risk industries, there is a need to develop a model to describe, understand, explain, and predict interruptions …

Register Now: May 8 - Vanishing Bits And Bytes Conference, Vol.4 (2) March - April 2006, Houston Academy Of Medicine-Texas Medical Center Library

The Insider (2003-2008)

No abstract provided.

Insider Express, Houston Academy Of Medicine-Texas Medical Center Library

Insider Express (2003-2013)

No abstract provided.

Gsbs News, Spring 2006, Graduate School Of Biomedical Sciences, University Of Texas Health Science Center At Houston/M.D. Anderson Cancer Center

GSBS News

No abstract provided.

Comparison Of Og1rf And An Isogenic Fsrb Deletion Mutant By Transcriptional Analysis: The Fsr System Of Enterococcus Faecalis Is More Than The Activator Of Gelatinase And Serine Protease, Agathe Bourgogne, Susan G Hilsenbeck, Gary M Dunny, Barbara E Murray

Faculty, Staff and Student Publications

The FsrABC system of Enterococcus faecalis controls the expression of gelatinase and a serine protease via a quorum-sensing mechanism, and recent studies suggest that the Fsr system may also regulate other genes important for virulence. To investigate the possibility that Fsr influences the expression of additional genes, we used transcriptional profiling, with microarrays based on the E. faecalis strain V583 sequence, to compare the E. faecalis strain OG1RF with its isogenic mutant, TX5266, an fsrB deletion mutant. We found that the presence of an intact fsrB influences expression of numerous genes throughout the growth phases tested, namely, late log to …

Bifurcation And Singularity Analysis Of A Molecular Network For The Induction Of Long-Term Memory, Hao Song, Paul Smolen, Evyatar Av-Ron, Douglas A. Baxter, John H H. Byrne

Faculty, Staff and Student Publications

Withdrawal reflexes of the mollusk Aplysia exhibit sensitization, a simple form of long-term memory (LTM). Sensitization is due, in part, to long-term facilitation (LTF) of sensorimotor neuron synapses. LTF is induced by the modulatory actions of serotonin (5-HT). Pettigrew et al. developed a computational model of the nonlinear intracellular signaling and gene network that underlies the induction of 5-HT-induced LTF. The model simulated empirical observations that repeated applications of 5-HT induce persistent activation of protein kinase A (PKA) and that this persistent activation requires a suprathreshold exposure of 5-HT. This study extends the analysis of the Pettigrew model by applying …

Abnormal Expression Of Rest/Nrsf And Myc In Neural Stem/Progenitor Cells Causes Cerebellar Tumors By Blocking Neuronal Differentiation, Xiaohua Su, Vidya Gopalakrishnan, Duncan Stearns, Kenneth Aldape, Fredrick F Lang, Gregory Fuller, Evan Snyder, Charles G Eberhart, Sadhan Majumder

Faculty, Staff and Student Publications

Medulloblastoma, one of the most malignant brain tumors in children, is thought to arise from undifferentiated neural stem/progenitor cells (NSCs) present in the external granule layer of the cerebellum. However, the mechanism of tumorigenesis remains unknown for the majority of medulloblastomas. In this study, we found that many human medulloblastomas express significantly elevated levels of both myc oncogenes, regulators of neural progenitor proliferation, and REST/NRSF, a transcriptional repressor of neuronal differentiation genes. Previous studies have shown that neither c-Myc nor REST/NRSF alone could cause tumor formation. To determine whether c-Myc and REST/NRSF act together to cause medulloblastomas, we used a …

Hepatic And Renal Cytochrome P450 Gene Regulation During Citrobacter Rodentium Infection In Wild-Type And Toll-Like Receptor 4 Mutant Mice, Terrilyn A Richardson, Melanie Sherman, Leposava Antonovic, Sean S Kardar, Henry W Strobel, Daniel Kalman, Edward T Morgan

Faculty, Staff and Student Publications

Citrobacter rodentium is the rodent equivalent of human enteropathogenic Escherichia coli infection. This study investigated regulation of hepatic and renal cytochrome P450 (P450) mRNAs, hepatic P450 proteins, cytokines, and acute phase proteins during C. rodentium infection. Female C3H/HeOuJ (HeOu) and C3H/HeJ (HeJ) mice [which lack functional toll-like receptor 4 (TLR4)] were infected with C. rodentium by oral gavage and sacrificed 6 days later. Hepatic CYP4A10 and 4A14 mRNAs were decreased in HeOu mice (

Insider Express, Houston Academy Of Medicine-Texas Medical Center Library

Insider Express (2003-2013)

No abstract provided.