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2009

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Articles 1 - 30 of 421

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Chromatin 'Programming' By Sequence - Is There More To The Nucleosome Code Than %Gc, Amanda Hughes, Oliver J. Rando Dec 2009

Chromatin 'Programming' By Sequence - Is There More To The Nucleosome Code Than %Gc, Amanda Hughes, Oliver J. Rando

Open Access Articles

The role of genomic sequence in directing the packaging of eukaryotic genomes into chromatin has been the subject of considerable recent debate. A new paper from Tillo and Hughes shows that the intrinsic thermodynamic preference of a given sequence in the yeast genome for the histone octamer can largely be captured with a simple model, and in fact is mostly explained by %GC. Thus, the rules for predicting nucleosome occupancy from genomic sequence are much less complicated than has been claimed.


Structural Studies Of Large Integral Membrane Proteins In Reverse Micelles By Solution Nuclear Magnetic Resonance, Joseph Kielec Dec 2009

Structural Studies Of Large Integral Membrane Proteins In Reverse Micelles By Solution Nuclear Magnetic Resonance, Joseph Kielec

Publicly Accessible Penn Dissertations

The structural characterization of integral membrane proteins represents one of the many challenges of the post-genomic era. While membrane proteins comprise approximately 50% of current and potential drug targets, their structural characterization lags far behind that of soluble proteins. Nuclear magnetic resonance (NMR) offers tremendous potential for the investigation of membrane proteins in aqueous environments with respect to structural characterization, relaxation properties, and the details of small ligand interactions. However, the size limitations of solution NMR due to the slow tumbling problem have restricted comprehensive structural characterization of membrane protein NMR structures to the relatively small β-barrel proteins or helical ...


Effect Of Hydration And Macromolecular Crowding On Peptide Conformation, Aggregation And Folding Kinetics, Smita Mukherjee Dec 2009

Effect Of Hydration And Macromolecular Crowding On Peptide Conformation, Aggregation And Folding Kinetics, Smita Mukherjee

Publicly Accessible Penn Dissertations

Protein folding/misfolding in vivo takes place in a highly crowded and confined environment. Such crowded environment can possibly lead to fewer water molecules surrounding a protein of interest than that seen under in vitro conditions wherein typically dilute aqueous solutions are used. When considering the aforesaid cellular characteristics, such as water depletion and macromolecular crowding; it is reasonable to assume that proteins may experience different energy landscapes when folding in vivo than in vitro. Therefore, we have investigated how degrees of hydration and macromolecular crowding affect the conformation, aggregation and folding kinetics of short peptides.

In order to modulate ...


Nf-Kappab Signaling Pathways In Mammalian And Insect Innate Immunity, Neal S. Silverman, Tom Maniatis Dec 2009

Nf-Kappab Signaling Pathways In Mammalian And Insect Innate Immunity, Neal S. Silverman, Tom Maniatis

Neal Silverman

In this review, we discuss recent advances in understanding the signaling pathways in mammalian and Drosophila innate immunity, with emphasis on the mechanisms by which NF-kappaB/Rel family proteins are activated.


Shortest Geometric Paths Analysis In Structural Biology, Ryan G. Coleman Dec 2009

Shortest Geometric Paths Analysis In Structural Biology, Ryan G. Coleman

Publicly Accessible Penn Dissertations

The surface of a macromolecule, such as a protein, represents the contact point of any interaction that molecule has with solvent, ions, small molecules or other macromolecules. Analyzing the surface of macromolecules has a rich history but analyzing the distances from this surface to other surfaces or volumes has not been extensively explored. Many important questions can be answered quantitatively through these analyses. These include: what is the depth of a pocket or groove on the surface? what is the overall depth of the protein? how deeply are atoms buried from the surface? where are the tunnels in a protein ...


The Danger Signal Adenosine Induces Persistence Of Chlamydial Infection Through Stimulation Of A2b Receptors, Matthew A. Pettengill, Verissa W. Lam, David M. Ojcius Dec 2009

The Danger Signal Adenosine Induces Persistence Of Chlamydial Infection Through Stimulation Of A2b Receptors, Matthew A. Pettengill, Verissa W. Lam, David M. Ojcius

Dugoni School of Dentistry Faculty Articles

Infections with intracellular bacteria such as chlamydiae affect the majority of the world population. Infected tissue inflammation and granuloma formation help contain the short-term expansion of the invading pathogen, leading also to local tissue damage and hypoxia. However, the effects of key aspects of damaged inflamed tissues and hypoxia on continued infection with intracellular bacteria remain unknown. We find that development of Chlamydia trachomatis is reversibly retarded by prolonged exposure of infected cells to extracellular adenosine, a hallmark of hypoxia and advanced inflammation. In epithelial cells, this effect was mediated by the A2b adenosine receptor, unique in the adenosine receptor ...


Progress Toward The Total Synthesis Of Lyconadin A, Yu Zhang Dec 2009

Progress Toward The Total Synthesis Of Lyconadin A, Yu Zhang

Theses and Dissertations

Lyconadin A is a pentacyclic Lycopodium alkaloid isolated from the club moss Lycopodium complanatum with antitumor properties. We have developed a novel 7-exo/6-exo acyl radical cascade cyclization as a method of making the bicyclo[5.4.0]undecane ring system of lyconadin A. The model products are trans-fused ring systems, while a cis-fused ring system is needed in lyconadin A. We have discovered a method to convert the trans-fused model cascade cyclization product into the desired cis isomer. Based on Donohoe's pyridone synthesis, we developed a method for the construction of 5-alkyl and ...


Nucleotide And Phospholipid-Dependent Control Of Ppxd And C-Domain Association For Seca Atpase, Don Oliver Dec 2009

Nucleotide And Phospholipid-Dependent Control Of Ppxd And C-Domain Association For Seca Atpase, Don Oliver

Don Oliver

The SecA ATPase motor is a central component of the eubacterial protein translocation machinery. It is comprised of N- and C-domain substructures, where the N-domain is comprised of two nucleotide-binding domains that flank a preprotein-binding domain (PPXD), while the C-domain binds phospholipids as well as SecB chaperone. Our recent crystal structure of Bacillus subtilis SecA protomer [Hunt, J. F., Weinkauf, S., Henry, L., Fak, J. J., McNicholas, P., Oliver, D. B., and Deisenhofer, J. (2002) Science 297, 2018-2026] along with experimental support for the correct dimer structure [Ding, H., Hunt, J. F., Mukerji, I., and Oliver, D. (2003) Biochemistry 42 ...


Role Of A Conserved Glutamate Residue In The Escherichia Coli Seca Atpase Mechanism, Don Oliver Dec 2009

Role Of A Conserved Glutamate Residue In The Escherichia Coli Seca Atpase Mechanism, Don Oliver

Don Oliver

Escherichia coli SecA uses ATP to drive the transport of proteins across cell membranes. Glutamate 210 in the "DEVD" Walker B motif of the SecA ATP-binding site has been proposed as the catalytic base for ATP hydrolysis (Hunt, J. F., Weinkauf, S., Henry, L., Fak, J. J., McNicholas, P., Oliver, D. B., and Deisenhofer, J. (2002) Science 297, 2018-2026). Consistent with this hypothesis, we find that mutation of glutamate 210 to aspartate results in a 90-fold reduction of the ATP hydrolysis rate compared with wild type SecA, 0.3 s(-1) versus 27 s(-1), respectively. SecA-E210D also releases ADP ...


Dimeric Seca Is Essential For Protein Translocation, Don Oliver Dec 2009

Dimeric Seca Is Essential For Protein Translocation, Don Oliver

Don Oliver

SecA facilitates bacterial protein translocation by its association with presecretory or membrane proteins and the SecYEG translocon channel. Once assembled, SecA ATPase undergoes cycles of membrane insertion and retraction at SecYEG that drive protein translocation in a stepwise fashion. SecA exists in equilibrium between a monomer and dimer, and association with its translocation ligands shifts this equilibrium dramatically. Here, we examined the proposal that protein translocation can occur by means of a SecA monomer. We produced a mutant SecA protein lacking residues 2-11, which was found to exist mostly as a monomer, and it was unable to complement a conditional-lethal ...


Muc4/Muc4 Functions And Regulation In Cancer., Goldi Kozloski Dec 2009

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

Goldi A Kozloski

The membrane mucin MUC4 (human) is abundantly expressed in many epithelia, where it is proposed to play a protective role, and is overexpressed in some epithelial tumors. Studies on the rat homologue, Muc4, indicate that it acts through anti-adhesive or signaling mechanisms. In particular, Muc4/MUC4 can serve as a ligand/modulator of the receptor tyrosine kinase ErbB2, regulating its phosphorylation and the phosphorylation of its partner ErbB3, with or without the involvement of the ErbB3 ligand neuregulin. Muc4/MUC4 can also modulate cell apoptosis via multiple mechanisms, both ErbB2 dependent and independent. Muc4/MUC4 expression is regulated by multiple ...


Structural Studies Of Two Related Metallohydrolases: Human Histone Deacetylase 8 And Malarial Arginase, Daniel P. Dowling Dec 2009

Structural Studies Of Two Related Metallohydrolases: Human Histone Deacetylase 8 And Malarial Arginase, Daniel P. Dowling

Publicly Accessible Penn Dissertations

Metal-dependent histone deacetylases (HDACs) catalyze the deacetylation of lysine residues in histones and other proteins in eukaryotic cells. Isozyme HDAC8 is perhaps the archetypical member of the class I HDAC family and serves as a paradigm for studying structure-function relationships. We report the structures of HDAC8 complexes in a new crystal form. Comparison of unliganded and liganded structures illustrates ligand-induced conformational changes in the L2-loop that likely accompany substrate binding and catalysis. These structures, along with four D101 variants, support the proposal that D101 is critical for the function of the L2 loop. Additionally, the structure of H143A HDAC8 complexed ...


Reexamination Of The Role Of The Amino Terminus Of Seca In Promoting Its Dimerization And Functional State, Don Oliver Dec 2009

Reexamination Of The Role Of The Amino Terminus Of Seca In Promoting Its Dimerization And Functional State, Don Oliver

Don Oliver

No abstract provided.


Seca Dimer Cross-Linked At Its Subunit Interface Is Functional For Protein Translocation, Don Oliver Dec 2009

Seca Dimer Cross-Linked At Its Subunit Interface Is Functional For Protein Translocation, Don Oliver

Don Oliver

SecA facilitates protein transport across the eubacterial plasma membrane by its association with cargo proteins and the SecYEG translocon, followed by ATP-driven conformational changes that promote protein translocation in a stepwise manner. Whether SecA functions as a monomer or a dimer during this process has been the subject of considerable controversy. Here we utilize cysteine-directed mutagenesis along with the crystal structure of the SecA dimer to create a cross-linked dimer at its subunit interface, which was normally active for in vitro protein translocation.


In Vivo Membrane Topology Of Escherichia Coli Seca Atpase Reveals Extensive Periplasmic Exposure Of Multiple Functionally Important Domains Clustering On One Face Of Seca, Don Oliver Dec 2009

In Vivo Membrane Topology Of Escherichia Coli Seca Atpase Reveals Extensive Periplasmic Exposure Of Multiple Functionally Important Domains Clustering On One Face Of Seca, Don Oliver

Don Oliver

No abstract provided.


Genetic Effect Of The Dwarfing Genes On Some Culm Characteristics Associatcd With Lodging Resistance In Bread Wheat, Md. Mahbub Hasan Dec 2009

Genetic Effect Of The Dwarfing Genes On Some Culm Characteristics Associatcd With Lodging Resistance In Bread Wheat, Md. Mahbub Hasan

Md. Mahbub Hasan

Due to the challenge of screening traits related to lodging resistance under natural field conditions, selection for lodging resistant varieties in wheat breeding programs is difficult. The identification of easily measurable culm anatomical traits related to lodging resistance would simplify the selection process. The present study was conducted to determine the effect of dwarfing genes on culm anatomical traits related to lodging resistance in our of basal internode 1. Field and laboratory study was conducted in Shahjalal University of Science and Technology, Sylhet, Bangladesh with eight wheat genotypes having Rhr1, Rht2 dwarfing genes in them and a local land race ...


Do Aphid-Resistant Soybeans Need Insecticides For Maximum Yields?, Matthew O'Neal, Marianna Chiozza, Gustavo Macintosh Dec 2009

Do Aphid-Resistant Soybeans Need Insecticides For Maximum Yields?, Matthew O'Neal, Marianna Chiozza, Gustavo Macintosh

Proceedings of the Integrated Crop Management Conference

Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), was first identified in the U.S. in the state of Wisconsin in 2000 and rapidly spread through the north central region of the US. The pest can reduce soybean yield by diminishing photosynthesis rates and/or by inducing premature senescence. Both effects reduce seed yield and seed quality. Since its introduction in North America, insecticides have been the primary management tool used by growers when outbreaks occur, which are frequent despite the impact of predators commonly found in North American soybean fields. Although predatory insects can limit soybean aphid population growth, their ...


Seeing The Future: Biology Research Allows Undergraduates New Insight Into Their Own Futures, Merideth Krevosky, Jeffery Bowen Dec 2009

Seeing The Future: Biology Research Allows Undergraduates New Insight Into Their Own Futures, Merideth Krevosky, Jeffery Bowen

Bridgewater Review

No abstract provided.


The Role Of Multiple Ccaat-Binding Factors In Candida Albicans Gene Expression, Lashall Lynn Bates Dec 2009

The Role Of Multiple Ccaat-Binding Factors In Candida Albicans Gene Expression, Lashall Lynn Bates

Theses and Dissertations

The CCAAT-binding factor is a heterooligomeric transcription factor that is evolutionarily conserved in eukaryotes. In yeast, the DNA-binding component that interacts with the CCAAT consensus sequence in promoters consists of the subunits termed Hap2p, Hap3p and Hap5p. In yeast and fungi, a fourth subunit, Hap4p, is required for regulating gene expression. The goal of this research is to understand the function of the Candida albicans CCAAT-binding factor and how it relates to virulence and pathogenicity. C. albicans is a human opportunistic pathogen responsible for a variety of mucosal and systemic infections that result in significant morbidity and mortality, particularly in ...


The Physiological And Biochemical Understanding Of 5’-Amp Induced Deep Hypometabolism, William G. O'Brien Dec 2009

The Physiological And Biochemical Understanding Of 5’-Amp Induced Deep Hypometabolism, William G. O'Brien

UT GSBS Dissertations and Theses (Open Access)

Our laboratory’s ability to induce deep hypometabolism (DH) via an injection of adenosine monophosphate (5’-AMP) followed by placement in an ambient temperature (Ta) around 15oC currently can last about 3-9 hours. While we have insight into how 5’-AMP induced hypometabolism is initiated, it remains unclear how arousal from hypometabolism is controlled. Other laboratory members have been unable to prolong this process safely and effectively with previous attempts of re-injecting a dose of 5’-AMP upon arousal or by decreasing the Ta. While these methods worked in suppressing arousal, the mortality rate is also increased. To gather a ...


Overexpression And Partial Purification Of Serine Hydroxymethyltransferase, Kimberly Rose Stevens Dec 2009

Overexpression And Partial Purification Of Serine Hydroxymethyltransferase, Kimberly Rose Stevens

Chemistry and Biochemistry

No abstract provided.


Inactivation Of The Fliy Gene Encoding A Flagellar Motor Switch Protein Attenuates Mobility And Virulence Of Leptospira Interrogans Strain Lai, Sumei Liao, Ai-Hua Sun, David M. Ojcius, Senlin Wu, Jinfang Zhao, Jie Yan Dec 2009

Inactivation Of The Fliy Gene Encoding A Flagellar Motor Switch Protein Attenuates Mobility And Virulence Of Leptospira Interrogans Strain Lai, Sumei Liao, Ai-Hua Sun, David M. Ojcius, Senlin Wu, Jinfang Zhao, Jie Yan

Dugoni School of Dentistry Faculty Articles

Background: Pathogenic Leptospira species cause leptospirosis, a zoonotic disease of global importance. The spirochete displays active rotative mobility which may contribute to invasion and diffusion of the pathogen in hosts. FliY is a flagellar motor switch protein that controls flagellar motor direction in other microbes, but its role in Leptospira, and paricularly in pathogenicity remains unknown.

Results: A suicide plasmid for the fliY gene of Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai strain Lai that was disrupted by inserting the ampicillin resistance gene (bla) was constructed, and the inactivation of fliY gene in a mutant (fliY-) was confirmed by PCR and ...


Charge Switch Nucleotides, John G. K. Williams, Gregory R. Bashford, Jiyan Chen, Dan Draney, Nara Narayanan, Bambi Reynolds, Pamela Sheaff Dec 2009

Charge Switch Nucleotides, John G. K. Williams, Gregory R. Bashford, Jiyan Chen, Dan Draney, Nara Narayanan, Bambi Reynolds, Pamela Sheaff

Biomedical Imaging and Biosignal Analysis Laboratory

The present invention provides compounds, methods and systems for sequencing nucleic acid using single molecule detection. Using labeled NPs that exhibit charged-switching behavior, single-molecule DNA sequencing in a microchannel sorting system is realized. In operation, sequencing products are detected enabling real-time sequencing as successive detectable moieties flow through a detection channel. By electrically sorting charged molecules, the cleaved product molecules are detected in isolation Without interference from unincorporated NPs and Without illuminating the polymerase-DNA complex.


Association Between Structural Measures Of Specific Regional Brain Volumes Measured By Quantitative Magnetic Resonance Imaging And Neurocognitive Performance In Elderly Breast Cancer Survivors Exposed To Chemotherapy, Haris Hamsakutty Dec 2009

Association Between Structural Measures Of Specific Regional Brain Volumes Measured By Quantitative Magnetic Resonance Imaging And Neurocognitive Performance In Elderly Breast Cancer Survivors Exposed To Chemotherapy, Haris Hamsakutty

Theses and Dissertations

Recent advances in early detection and treatment of breast cancer have led to increasing numbers of long term survivors of breast cancer. There is a growing concern about the potential adverse effects of chemotherapy on cognitive functioning.

The current study examines the neuroanatomical correlates of late neurocognitive effects of chemotherapy in elderly breast cancer survivors who have survived more than ten years and were exposed to chemotherapy at the time of their cancer treatment.

The participants in this study are 30 women breast cancer survivors in the age range of 65-81 years. In this cross sectional design, regional brain volumes ...


Recognition Of Calcineurin By The Domains Of Calmodulin: Thermodynamic And Structural Determinants, Susan Ellen O'Donnell Dec 2009

Recognition Of Calcineurin By The Domains Of Calmodulin: Thermodynamic And Structural Determinants, Susan Ellen O'Donnell

Theses and Dissertations

Calcineurin (CaN), a heterodimeric Ca2+-calmodulin-dependent Ser/Thr phosphatase, regulates diverse pathways, from stress responses in yeast to T-cell activation and cardiac hypertrophy in humans. Calmodulin (CaM), an essential mediator of calcium–dependent signaling pathways, activates CaN in the presence of calcium by binding to an intrinsically disordered region of the enzyme and altering its conformation. My hydrodynamic studies have determined that CaM participates in a 1:1 complex with the CaM-binding domain of βCaN (CaNp, residues 400–423).

To explore the molecular mechanism of CaM association with CaN, I have used spectroscopic methods to determine the calcium-dependent and domain ...


Insights Into The Allosteric Interactions Within The Actin Molecule, Ema Stokasimov Dec 2009

Insights Into The Allosteric Interactions Within The Actin Molecule, Ema Stokasimov

Theses and Dissertations

Actin's ability to engage in a wide range of physiological functions requires that it be subject to complex spatial and temporal regulation. This regulation is achieved internally through monomer-monomer contacts and externally through interactions with actin binding proteins. The first part of my thesis focused on better understanding the role of inter-monomeric ionic interactions proposed between subdomains 2 and 3 of opposing monomers in F-actin stabilization. I studied several yeast actin mutants: A167R to disrupt a proposed ionic attraction with R39, A167E to mimic a proposed ionic attraction in muscle actin, and D275R to disrupt a proposed ionic attraction ...


Genetic Pathways Of Lyst And Exfoliation Syndrome, Colleen Trantow Dec 2009

Genetic Pathways Of Lyst And Exfoliation Syndrome, Colleen Trantow

Theses and Dissertations

Human eyes with exfoliation syndrome (XFS) exhibit a distinctive pattern of iris transillumination defects that are recapitulated in Lyst mutant mice carrying the beige allele. Here I present the identification and characterization of the B6-Lystbg-J mouse model of XFS, modifiers of Lyst mediated ocular phenotypes, mechanisms of intraocular pressure (IOP) pathology related to circadian rhythms, and mechanisms of iris transillumination defects in the B6-Lystbg-J mice.

Clinical and histological analysis shows that the B6-Lystbg-J mice have multiple similarities to human XFS including: iris transillumination defects, production of an exfoliative-like material, and pronounced pigment dispersion. Despite ...


Cloning And Expression Of Porcine Dicer And Argonaute-2, Heather Stowe Dec 2009

Cloning And Expression Of Porcine Dicer And Argonaute-2, Heather Stowe

All Theses

In vitro-produced embryos exhibit aberrations in development, but the reasons for these developmental problems are unknown. Recently, a class of small non-coding RNA called microRNA (miRNA) has been described and reported to have roles in normal mammalian embryonic development. These miRNAs are encoded in the genome, transcribed by RNA pol II and processed into fragments approximately 22 nt in length by ribonuclease enzymes, the final one being a protein called Dicer. miRNA work through the RNA-induced silencing complex (RISC), of which the argonaute gene family are key proteins. Argonaute-2 (Ago2) has been identified as the only member possessing endonuclease activity ...


Low-Dose Of Sodium Arsenite Causes Delayed Differentiation In C2c12 Mouse Myoblast Cells Through The Repression Of The Transcription Factor Myogenin, Amanda Steffens Dec 2009

Low-Dose Of Sodium Arsenite Causes Delayed Differentiation In C2c12 Mouse Myoblast Cells Through The Repression Of The Transcription Factor Myogenin, Amanda Steffens

All Theses

A number of epidemiological studies have correlated arsenic exposurwith cancer, skin diseases, cardiovascular diseases, and adverse developmental outcomes such as stillbirths, spontaneous abortions, neonatal mortality, low birth weight, and delays in the use of musculature. The current study used C2C12 mouse myoblast cells to examine whether low concentrations of arsenic could alter their differentiation into myotubes, which would indicate that arsenic has the ability to act as a developmental toxicant. Myoblast cells were exposed to 20nM sodium arsenite and allowed to differentiate into myotubes and expression of the muscle-specific transcription factor myogenin, along with the expression of myosin light chain ...


Light-Related Photosynthetic Gene Expression And Enzyme Activity In The Heterokont Alga Vaucheria Litorea And Its Symbiotic Partner The Sacoglossan Mollusc Elysia Chlorotica, Kara M. Soule Dec 2009

Light-Related Photosynthetic Gene Expression And Enzyme Activity In The Heterokont Alga Vaucheria Litorea And Its Symbiotic Partner The Sacoglossan Mollusc Elysia Chlorotica, Kara M. Soule

Electronic Theses and Dissertations

Photosynthesis is comprised of tightly coupled reactions and therefore requires strict matrices of regulation, particularly involving alterations in gene expression and enzyme activity within the nucleus and plastid. Extensive research has been carried out on these light-regulated mechanisms in plants and green algae, however, much less is known in the red algal lineage, including heterokonts. The goal of this study was to investigate the influence of light on photosynthetic gene expression and select enzyme activity in the heterokont alga Vaucheria litorea and its symbiotic partner Elysia chlorotica, a photosynthetic sacoglossan mollusc (sea slug). Elysia chlorotica harbors V. litorea plastids intracellularly ...