Molecular Biology Commons^™

A Specific Regulatory Role For Sgtα On The Maturation And Activation Of Steroid Hormone Receptors, Atanu Paul

Open Access Theses & Dissertations

Steroid hormone receptors (SHRs) are ligand-dependent transcription factors belonging to the nuclear receptor superfamily. These receptors regulate various physiological functions in higher ordered eukaryotes. In the absence of hormone these receptors form a complex with molecular chaperones such as Hsp90 and Hsp70 and other cochaperones in the cytoplasm. Association with the Hsp90-Hsp70 chaperone machinery leads to the maturation of the Ligand Binding Domain (LBD) of the receptors and enables the receptors to bind hormone with high affinity. Upon binding with a specific hormone the receptors are translocated into the nucleus where they initiate transcription of specific genes. Although the involvement …

The Interictal State In Epilepsy And Behavior, Daniel Tice Barkmeier

Wayne State University Dissertations

Epilepsy is one of the most common neurological diseases, affecting up to 1% of the world population. Epilepsy remains poorly understood and there are currently no medications to cure it. Patients with epilepsy have both seizures as well as another type of abnormal activity between seizures, known as interictal spikes. Interictal spikes have thus far been poorly researched, yet growing evidence supports an important role for them in epilepsy. In this project, we first show the high variability between reviewers in marking interictal spikes on intracranial EEG, and then develop and test an automated detection method to solve this problem. …

Prospects And Pits On The Path Of Biomimetics: The Case Of Tooth Enamel, Vuk Uskoković

Pharmacy Faculty Articles and Research

This review presents a discourse on challenges in understanding and imitating the process of amelogenesis in vitro on the molecular scale. In light of the analysis of imitation of the growth of dental enamel, it also impends on the prospects and potential drawbacks of the biomimetic approach in general. As the formation of enamel proceeds with the protein matrix guiding the crystal growth, while at the same time conducting its own degradation and removal, it is argued that three aspects of amelogenesis need to be induced in parallel: a) crystal growth; b) protein assembly; c) proteolytic degradation. A particular emphasis …

Muc4/Muc4 Functions And Regulation In Cancer., Goldi Kozloski

Goldi A Kozloski

Computational Prediction Of The Agregated Structure Of Denatured Lysozyme, Pongsathorn Chotikasemsri

Masters Theses & Specialist Projects

Mis-folded proteins and their associated aggregates are a contributing factor in some human diseases. In this study we used the protein lysozyme as a model to define aggregation structures under denaturing conditions. Sasahara et al. (2007), Frare et al. (2009, 2006), and Rubin et al. (2008) observed conditions where heat denatured lysozyme formed fibril structures that were observed to be 8-17 nanometers in diameter under the electron microscope. Even though the crystal structure of lysozyme is known, the denatured form of this protein is still unknown. Therefore, we used Rosetta++ protein folding and blind docking software to create in silico …

Trnas: Cellular Barcodes For Amino Acids, Ranat Banerjee, Shawn Chen, Kiley Dare, Marla Gilreath, Mette Praetorius-Ibba, Medha Raina, Noah M. Reynolds, Theresa E. Rogers, Hervé Roy, Srujana S. Yadavalli, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The role of tRNA in translating the genetic code has received considerable attention over the last 50 years, and we now know in great detail how particular amino acids are specifically selected and brought to the ribosome in response to the corresponding mRNA codon. Over the same period, it has also become increasingly clear that the ribosome is not the only destination to which tRNAs deliver amino acids, with processes ranging from lipid modification to antibiotic biosynthesis all using aminoacyl‐tRNAs as substrates. Here we review examples of alternative functions for tRNA beyond translation, which together suggest that the role of …

Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

No abstract provided.

Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr

Maria Cekanova MS, RNDr, PhD

No abstract provided.

Broad Range Amino Acid Specificity Of Rna-Dependent Lipid Remodelling By Multiple Peptide Resistance Factors, Hervé Roy, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacylphosphatidylglycerol synthases (aaPGSs) are multiple peptide resistance factors that transfer amino acids from aminoacyl-tRNAs to phosphatidylglycerol (PG) in the cytoplasmic membrane. Aminoacylation of PG is used by bacteria to decrease the net negative charge of the cell envelope, diminishing affinity for charged molecules and allowing for adaptation to environmental changes. Lys-PGS, which transfers lysine to PG, is essential for the virulence of certain pathogens, providing resistance to both host cationic antimicrobial peptides and therapeutic antibiotics. Ala-PGS was also recently described, but little is known about the possible activities of other members of the highly diverse aaPGS family of proteins. Systematic …

The Cca Anticodon Specifies Separate Functions Inside And Outside Translation In Bacillus Cereus, Sandro F. Ataide, Theresa E. Rogers, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacillus cereus 14579 encodes two tRNAs with the CCA anticodon, tRNA^Trp and tRNA^Other. tRNA^Trp was separately aminoacylated by two enzymes, TrpRS1 and TrpRS2, which share only 34% similarity and display different catalytic capacities and specificities. TrpRS1 was 18-fold more proficient at aminoacylating tRNA^Trp with Trp, while TrpRS2 more efficiently utilizes the Trp analog 5-hydroxy Trp. tRNA^Other was not aminoacylated by either TrpRS but instead by the combined activity of LysRS1 and LysRS2, which recognized sequence elements absent from tRNA^Trp. Polysomes were found to contain tRNA^Trp, consistent with its role in …

E-Science @ Umass: Anticipating And Supporting E-Science Activities At The University Of Massachusetts, Maxine G. Schmidt, Rebecca Reznik-Zellen

Maxine G Schmidt

In March of 2008 an Ad Hoccommittee of Science Librarians from the University of Massachusetts Five Campus System convened to discuss the challenges of e-science and prepare the Libraries for their role in e-science initiatives. Three primary outcomes intended to support e-science activities emerged from the work of the Ad Hoc committee.

Inhibition Of Yeast Hexokinase By The Antimalarial Drug Artemisinin: Probing Mechanism Of Action With A Model Enzyme, Jennifer S. Spence

Biological Sciences Theses & Dissertations

A leading infectious cause of death, malaria threatens approximately half of the world's population, and drug-resistant strains of Plasmodium falciparum have created immense difficulty in chemotherapy of the disease. The artemisinin (ART) class of antimalarials may represent a powerful solution. In addition to their safety, effectiveness, and moderate cost, they are the only drugs in use for which there has been no widespread evidence of clinical resistance. The exact parasiticidal mechanism of ART is highly contested, but evidence suggests that protein alkylation may play a role in cytotoxicity. in vitro essays were performed using yeast hexokinase (HK) to demonstrate a …

Effects Of Estrogen On Muscle Damage In Response To An Acute Resistance Exercise Protocol, Megan R. Wolf

Honors Scholar Theses

Creatine Kinase (CK) is used as a measure of exercise-induced muscle membrane damage. During acute eccentric (muscle lengthening) exercise, muscle sarcolemma, sarcoplasmic reticulum, and Z-lines are damaged, thus causing muscle proteins and enzymes to leak into the interstitial fluid.

Strenuous eccentric exercise produces an elevation of oxygen free radicals, which further increases muscle damage. Muscle soreness and fatigue can be attributed to this membrane damage. Estradiol, however, may preserve membrane stability post-exercise (Brancaccio, Maffulli, & Limongelli, 2007; Carter, Dobridge, & Hackney, 2001; Tiidus, 2001). Because estradiol has a similar structure to Vitamin E, which is known to have antioxidant properties, …

Identifying Biomarkers For Resistance To Novel Cisplatin Analogues In Human Lung, Breast And Prostate Cancers, Becky Michelle Hess

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cisplatin is a common therapeutic agent used in cancer treatment. Unfortunately, resistance to cisplatin in addition to severe side effects limits its use in cancer treatment. Two novel cisplatin analogues, 4DB and 4TB were shown to have varying cytotoxicity in lung, breast and prostate cancer cells. The hypothesis for this study states that the differences in 4DB and 4TB cytotoxicity among different tissue types is due to the type and efficiency of DNA repair mechanisms involved in response to these drugs.

To test the hypothesis, proteins involved in the rate limiting step of nucleotide excision repair (NER) and mismatch repair …

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

Resampling And Editing Of Mischarged Trna Prior To Translation Elongation, Jiqiang Ling, Byung Ran So, Srujana S. Yadavalli, Hervé Roy, Shinichiro Shoji, Kurt Fredrick, Karin Musier-Forsyth, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Faithful translation of the genetic code depends on the GTPase EF-Tu delivering correctly charged aminoacyl-tRNAs to the ribosome for pairing with cognate codons. The accurate coupling of cognate amino acids and tRNAs by the aminoacyl-tRNA synthetases is achieved through a combination of substrate specificity and product editing. Once released by aminoacyl-tRNA synthetases, both cognate and near-cognate aminoacyl-tRNAs were considered to be committed to ribosomal protein synthesis through their association with EF-Tu. Here we show instead that aminoacyl-tRNAs in ternary complex with EF-Tu•GTP can readily dissociate and rebind to aminoacyl-tRNA synthetases. For mischarged species, this allows resampling by the product editing …

E-Science @ The University Of Massachusetts, Maxine G. Schmidt, Rebecca Reznik-Zellen, Raquel Rivera, Cecilia P. Mullen

Maxine G Schmidt

e-Science @ the University of Massachusetts Abstract: What is e-Science and how can libraries and librarians support it? The University of Massachusetts takes a proactive approach to support network-enabled research on its campuses and provides examples where e-Science is already at work. Statement: “e-Science” is a term commonly used to describe research in a networked environment, a growing trend not only in the sciences, but the arts and humanities as well. e-Science creates both opportunities and challenges for academic libraries. The opportunities lie in leveraging the basic skill set that libraries and librarians already possess: the knowledge of and practical …

Adaptation Of The Bacterial Membrane To Changing Environments Using Aminoacylated Phospholipids, Hervé Roy, Kiley Dare, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Fine‐tuning of the biophysical properties of biological membranes is essential for adaptation of cells to changing environments. For instance, to lower the negative charge of the lipid bilayer, certain bacteria add lysine to phosphatidylglycerol (PG) converting the net negative charge of PG (−1) to a net positive charge in Lys‐PG (+1). Reducing the net negative charge of the bacterial cell wall is a common strategy used by bacteria to resist cationic antimicrobial peptides (CAMPs) secreted by other microbes or produced by the innate immune system of a host organism. The article by Klein et al. in the current issue of …

Microscopic Analysis Of Sympathetic And Parasympathetic Distribution, Terminal Morphology, And Interaction In Whole-Mount Atria, Scott Harden

Electronic Theses and Dissertations

The sympathetic (SNS) and parasympathetic (PSNS) branches of the autonomic nervous system (ANS) innervate the heart, exerting excitatory and inhibitory influences (respectively) over cardiac functions (heart rate, AV conduction velocity, and contractility). However, the distribution and structure of SNS and PSNS innervation has not yet been well studied. Detailed characterization of the distributional organization and structural morphology of the SNS and PSNS in normal states is essential to the study of pathological autonomic remodeling. The present study utilized double immunohistochemical labeling techniques to examine tyrosine hydroxylase (TH) immunoreactive (IR) SNS and vesicular acetylcholine transporter (VAChT) IR PSNS axons and terminal …

Umass Libraries 2009, Maxine G. Schmidt

Maxine G Schmidt

No abstract provided.

Hmgb1 Mediates Endogenous Tlr2 Activation And Brain Tumor Regression, James Curtin, Naiyou Liu, Marianela Candolfi, Weidong Xiong, Hikmat Assi, Kader Yagiz, Matthew Edwards, Kathrin Michelsen, Kurt Kroeger, Chunyan Liu, Akm Ghulam Muhammad, Mary Clark, Moshe Arditi, Begonya Comin-Anduix, Antoni Ribas, Pedro Lowenstein, Maria Castro

Articles

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor that carries a 5-y survival rate of 5%. Attempts at eliciting a clinically relevant anti-GBM immune response in brain tumor patients have met with limited success, which is due to brain immune privilege, tumor immune evasion, and a paucity of dendritic cells (DCs) within the central nervous system. Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1), an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2) signaling …

Understanding The Physical Properties That Control Protein Crystallization By Analysis Of Largescale Experimental Data, W. Nicholson Price Ii, Yang Chen, Samuel K. Handelman, Helen Neely, Philip Manor, Richard Karlin, Rajesh Nair, Jinfeng Liu, Michael Baran, John Everett, Saichiu N. Tong, Farhad Forouhar, Swarup S. Swaminathan, Thomas Acton, Rong Xiao, Joseph R. Luft, Angela Lauricella, George T. Detitta, Burkhard Rost, Gaetano T. Montelione, John T. Hunt

Law Faculty Scholarship

Crystallization is the most serious bottleneck in high-throughput protein-structure determination by diffraction methods. We have used data mining of the large-scale experimental results of the Northeast Structural Genomics Consortium and experimental folding studies to characterize the biophysical properties that control protein crystallization. This analysis leads to the conclusion that crystallization propensity depends primarily on the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. We identify specific sequence features that correlate with crystallization propensity and that can be used to estimate the crystallization probability of a given construct. Analyses of …

Molecular Characterisation Of A Bovine-Like Rotavirus Detected From A Giraffe, Emily Mulherin, Jill Bryan, Marijke Beltman, Luke O'Grady, Eugene Pidgeon, Lucie Garon, Andrew Lloyd, John Bainbridge, Helen O'Shea, Paul Whyte, Séamus Fanning

Department of Biological Sciences Publications

Background

Rotavirus (RV), is a member of the Reoviridae family and an important etiological agent of acute viral gastroenteritis in the young. Rotaviruses have a wide host range infecting a broad range of animal species, however little is known about rotavirus infection in exotic animals. In this paper we report the first characterisation of a RV strain from a giraffe calf.

Results

This report describes the identification and detailed molecular characterisation of a rotavirus strain detected from a 14-day-old Giraffe (Giraffa camelopardalis), presenting with acute diarrhea. The RV strain detected from the giraffe was characterized molecularly as G10P[11]. …

Dynamics Of Apomyoglobin In The Α-To-Β Transition And Of Partially Unfolded Aggregated Protein, E. Fabiani, A. M. Stadler, D. Madern, M. M. Koza, M. Tehei, M. Hirai, G. Zaccai

Faculty of Science - Papers (Archive)

Changes of molecular dynamics in the α-to-β transition associated with amyloid fibril formation were explored on apo-myoglobin (ApoMb) as a model system. Circular dichroism, neutron and X-ray scattering experiments were performed as a function of temperature on the protein, at different solvent conditions. A significant change in molecular dynamics was observed at the α-to-β transition at about 55 ˚C, indicating a more resilient high temperature β structure phase. A similar effect at approximately the same temperature was observed in holo-myoglobin, associated with partial unfolding and protein aggregation. A study in a wide temperature range between 20 K and 360 K …

Curriculum Vitae, Robert P. Lane

Robert P. Lane

No abstract provided.

Aminoacyl-Trna Synthetase Complexes: Molecular Multitasking Revealed, Corinne D. Hausmann, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The accurate synthesis of proteins, dictated by the corresponding nucleotide sequence encoded in mRNA, is essential for cell growth and survival. Central to this process are the aminoacyl-tRNA synthetases (aaRSs), which provide amino acid substrates for the growing polypeptide chain in the form of aminoacyl-tRNAs. The aaRSs are essential for coupling the correct amino acid and tRNA molecules, but are also known to associate in higher order complexes with proteins involved in processes beyond translation. Multiprotein complexes containing aaRSs are found in all three domains of life playing roles in splicing, apoptosis, viral assembly, and regulation of transcription and translation. …

In Vivo Murine Melanoma Tumor Responses To Nanosecond Pulsed Electric Field Treatment, Xinhua Chen

Theses and Dissertations in Biomedical Sciences

High intensity nanosecond pulsed electric fields (nsPEF) were applied to melanoma tumors to observe functional and structural biological changes and to investigate the possible molecular mechanisms responsible. An animal model was set up by injecting B16F10 mouse melanoma cells into SKH-1 mice. A treatment (Tx) of 100 pulses: 300 nanosecond duration; 40 kV/cm field strength; at 0.5 Hz rate were delivered to melanoma tumors in 120 mice. The nsPEF Txcaused tumor self-destruction with sharply decreased cell volumes and shrunken nuclei. The apoptotic biochemical tests confirmed nsPEF Tx induced apoptosis in a time-dependent manner. Examination of gross vessel and micro-vessel density …

Structural And Functional Mapping Of The Archaeal Multi-Aminoacyl-Trna Synthetase Complex, Corinne D. Hausmann, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Methanothermobacter thermautotrophicus contains a multi-aminoacyl-tRNA synthetase complex (MSC) of LysRS, LeuRS and ProRS. Elongation factor (EF) 1A also associates to the MSC, with LeuRS possibly acting as a core protein. Analysis of the MSC revealed that LysRS and ProRS specifically interact with the idiosyncratic N- and C- termini of LeuRS, respectively. EF-1A instead interacts with the inserted CP1 proofreading domain, consistent with models for post-transfer editing by class I synthetases such as LeuRS. Together with previous genetic data, these findings show that LeuRS plays a central role in mediating interactions within the archaeal MSC by acting as a core scaffolding …

Writing Research Proposal: Literature Review And Database Search, Mamoudou H. Dicko Prof.

Pr. Mamoudou H. DICKO, PhD

Atf4 Is An Oxidative Stress–Inducible, Prodeath Transcription Factor In Neurons In Vitro And In Vivo, Philipp Lange, Juan Chavez, John T. Pinto, Giovanni Coppola, Chiao-Wang Sun, Tim Townes, Rajiv Ratan

NYMC Faculty Publications

Oxidative stress is pathogenic in neurological diseases, including stroke. The identity of oxidative stress-inducible transcription factors and their role in propagating the death cascade are not well known. In an in vitro model of oxidative stress, the expression of the bZip transcription factor activating transcription factor 4 (ATF4) was induced by glutathione depletion and localized to the promoter of a putative death gene in neurons. Germline deletion of ATF4 resulted in a profound reduction in oxidative stress-induced gene expression and resistance to oxidative death. In neurons, ATF4 modulates an early, upstream event in the death pathway, as resistance to oxidative …