Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Molecular Biology

2015

Institution
Keyword
Publication
Publication Type
File Type

Articles 1 - 30 of 434

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

Alternative Use Of Dna Binding Domains By The Neurospora White Collar Complex Dictates Circadian Regulation And Light Responses, Bin Wang, Xiaoying Zhou, Jennifer J. Loros, Jay C. Dunlap Dec 2015

Alternative Use Of Dna Binding Domains By The Neurospora White Collar Complex Dictates Circadian Regulation And Light Responses, Bin Wang, Xiaoying Zhou, Jennifer J. Loros, Jay C. Dunlap

Open Dartmouth: Faculty Open Access Scholarship

In the Neurospora circadian system, the White Collar complex (WCC) of WC-1 and WC-2 drives transcription of the circadian pacemaker gene frequency (frq), whose gene product, FRQ, as a part of the FRQ-FRH complex (FFC), inhibits its own expression. The WCC is also the principal Neurospora photoreceptor; WCC-mediated light induction of frq resets the clock, and all acute light induction is triggered by WCC binding to promoters of light-induced genes. However, not all acutely light-induced genes are also clock regulated, and conversely, not all clock-regulated direct targets of WCC are light induced; the structural determinants governing the shift from WCC ...


Endothelial Protein Kinase Map4k4 Promotes Vascular Inflammation And Atherosclerosis, Rachel J. Roth Flach, Athanasia Skoura, Anouch Matevossian, Laura V. Danai, Wei Zheng, Christian Cortes, Samit K. Bhattacharya, Myriam Aouadi, G. Nana Hagan, Joseph Yawe, Pranitha Vangala, Lorena Garcia Menendez, Marcus P. Cooper, Timothy P. Fitzgibbons, Leonard Buckbinder, Michael P. Czech Dec 2015

Endothelial Protein Kinase Map4k4 Promotes Vascular Inflammation And Atherosclerosis, Rachel J. Roth Flach, Athanasia Skoura, Anouch Matevossian, Laura V. Danai, Wei Zheng, Christian Cortes, Samit K. Bhattacharya, Myriam Aouadi, G. Nana Hagan, Joseph Yawe, Pranitha Vangala, Lorena Garcia Menendez, Marcus P. Cooper, Timothy P. Fitzgibbons, Leonard Buckbinder, Michael P. Czech

Program in Molecular Medicine Publications and Presentations

Signalling pathways that control endothelial cell (EC) permeability, leukocyte adhesion and inflammation are pivotal for atherosclerosis initiation and progression. Here we demonstrate that the Sterile-20-like mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), which has been implicated in inflammation, is abundantly expressed in ECs and in atherosclerotic plaques from mice and humans. On the basis of endothelial-specific MAP4K4 gene silencing and gene ablation experiments in Apoe(-/-) mice, we show that MAP4K4 in ECs markedly promotes Western diet-induced aortic macrophage accumulation and atherosclerotic plaque development. Treatment of Apoe(-/-) and Ldlr(-/-) mice with a selective small-molecule MAP4K4 inhibitor also markedly reduces atherosclerotic ...


Crispr Interference And Priming Varies With Individual Spacer Sequences, Chaoyou Xue, Arun S. Seetharam, Olga Musharova, Konstantin Severinov, Stan J. J. Brouns, Andrew J. Severin, Dipali G. Sashital Dec 2015

Crispr Interference And Priming Varies With Individual Spacer Sequences, Chaoyou Xue, Arun S. Seetharam, Olga Musharova, Konstantin Severinov, Stan J. J. Brouns, Andrew J. Severin, Dipali G. Sashital

Biochemistry, Biophysics and Molecular Biology Publications

CRISPR–Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated) systems allow bacteria to adapt to infection by acquiring ‘spacer’ sequences from invader DNA into genomic CRISPR loci. Cas proteins use RNAs derived from these loci to target cognate sequences for destruction through CRISPR interference. Mutations in the protospacer adjacent motif (PAM) and seed regions block interference but promote rapid ‘primed’ adaptation. Here, we use multiple spacer sequences to reexamine the PAM and seed sequence requirements for interference and priming in the Escherichia coli Type I-E CRISPR–Cas system. Surprisingly, CRISPR interference is far more tolerant of mutations in the seed ...


The Exocyst Subunit Sec6 Interacts With Assembled Exocytic Snare Complexes: A Dissertation, Michelle L. Dubuke Dec 2015

The Exocyst Subunit Sec6 Interacts With Assembled Exocytic Snare Complexes: A Dissertation, Michelle L. Dubuke

GSBS Dissertations and Theses

In eukaryotic cells, membrane-bound vesicles carry cargo between intracellular compartments, to and from the cell surface, and to the extracellular environment. Many conserved families of proteins are required for properly localized vesicle fusion, including the multi-subunit tethering complexes and the SNARE complexes. These protein complexes work together to promote proper vesicle fusion in other trafficking pathways. Contrary to these other pathways, our lab previously suggested that the exocyst subunit Sec6, a component of the exocytosis-specific tethering complex, inhibited Sec9:Sso1 SNARE complex assembly due to interactions in vitro with the SNARE protein Sec9 (Sivaram et al., 2005).

My goal for ...


A Novel Transcription Factor In Arabidopsis Thaliana Abiotic Stress Response, Achira S. Weerathunga Arachchilage Dec 2015

A Novel Transcription Factor In Arabidopsis Thaliana Abiotic Stress Response, Achira S. Weerathunga Arachchilage

University of New Orleans Theses and Dissertations

Plants respond to environmental stress by altering their gene expression. Under stress conditions some genes are activated and some genes are repressed. Even though a lot of work has been done to understand mechanisms of gene activation under abiotic stress very little information is available on how stress responsive genes are kept repressed under normal growth conditions. Recent work has revealed that plants use transcriptional repression as common mechanism of gene repression. Transcriptional repression is achieved by recruitment co-repressor complexes to the target genes. Recent studies have revealed that the co-repressor LUH complexes with SLK1 and SLK2 to silence Arabidopsis ...


Control Of The Basal Recycling And Surface Expression Of Epidermal Growth Factor Receptor By The Endocytic Recycling Regulator Ehd1 Utilizing A Pathway Shared By Rusc2, Eric Tom Dec 2015

Control Of The Basal Recycling And Surface Expression Of Epidermal Growth Factor Receptor By The Endocytic Recycling Regulator Ehd1 Utilizing A Pathway Shared By Rusc2, Eric Tom

Theses & Dissertations

The epidermal growth factor receptor (EGFR) is a prototype receptor tyrosine kinase (RTK) and oncogene aberrantly expressed or mutated in solid tumors. Its surface expression is dynamically regulated. Display of an activation-competent pool is essential for response to ligands. Internalization and degradation of EGFR following stimulation has received the most attention, fewer studies have characterized the recycling arm of EGFR transit, basal traffic and surface display are poorly understood. Thus, we evaluated the endocytic recycling of EGFR for its therapeutic potential in EGFR driven cancers. The C-Terminal Eps15 homology (EH) domain-containing proteins have emerged as regulators of surface receptor recycling ...


Regulation Of The Transmembrane Mucin Muc4 By Wnt/Β-Catenin In Gastrointestinal Cancers, Priya Pai Dec 2015

Regulation Of The Transmembrane Mucin Muc4 By Wnt/Β-Catenin In Gastrointestinal Cancers, Priya Pai

Theses & Dissertations

The transmembrane mucin MUC4 is a high molecular weight glycoprotein that is expressed de novo in pancreatic ductal adenocarcinoma (PDAC). MUC4 has been shown to play a tumor-promoting role in malignancies such as PDAC, ovarian cancer and breast cancer. Unlike the normal pancreas, MUC4 is ordinarily expressed by goblet and absorptive cells in the normal colonic epithelium. However, its expression/role in colorectal cancer (CRC) is not well studied.

In this dissertation, the goal was to identify factor(s) that may differentially regulate MUC4 in these two disparate malignancies. Furthermore, in light of its pro-tumorigenic role in other malignancies, we ...


The Role Of Thymine Dna Glycosylase (Tdg) And Dna Demethylation In Tgf Beta Signaling, Matthew E.R. Maitland Dec 2015

The Role Of Thymine Dna Glycosylase (Tdg) And Dna Demethylation In Tgf Beta Signaling, Matthew E.R. Maitland

Electronic Thesis and Dissertation Repository

Prompted by findings that TGFβ stimulates thymine DNA glycosylase (TDG) dependent rapid DNA demethylation and activation of the CDKN2B gene, I investigated the global role of TDG and DNA demethylation in TGFβ signaling in HaCaT cells. Using dot blot analysis, I show that TGFβ treatment increases the global levels of 5-formylcytosine, an intermediate metabolite of active DNA demethylation. Characterization of genomic regions that undergo DNA demethylation and recruitment of TDG indicate that they are both frequent events, but only overlap at 11 genomic locations. I identified 440 TGFβ upregulated genes, 40 of which were bound by TDG and 169 that ...


Hepatitis C Virus: Structural Insights Into Protease Inhibitor Efficacy And Drug Resistance: A Dissertation, Djade I. Soumana Dec 2015

Hepatitis C Virus: Structural Insights Into Protease Inhibitor Efficacy And Drug Resistance: A Dissertation, Djade I. Soumana

GSBS Dissertations and Theses

The Hepatitis C Virus (HCV) is a global health problem as it afflicts an estimated 170 million people worldwide and is the major cause of viral hepatitis, cirrhosis and liver cancer. HCV is a rapidly evolving virus, with 6 major genotypes and multiple subtypes. Over the past 20 years, HCV therapeutic efforts have focused on identifying the best-in-class direct acting antiviral (DAA) targeting crucial components of the viral lifecycle, The NS3/4A protease is responsible for processing the viral polyprotein, a crucial step in viral maturation, and for cleaving host factors involved in activating immunity. Thus targeting the NS3/4A ...


Hd2d Is A Regulator Of Abscisic Acid Responses In Arabidopsis, Joshua A. Farhi Dec 2015

Hd2d Is A Regulator Of Abscisic Acid Responses In Arabidopsis, Joshua A. Farhi

Electronic Thesis and Dissertation Repository

Histone deacetylases have important roles in development and stress response in plants. To further investigate their function, the HD2D gene, of the plant specific HD2 family, was studied. An hd2d-1 mutant and two HD2D overexpression lines were used in this study. Germination was delayed in hd2d-1 and HD2D overexpression seeds only in the presence of ABA. HD2D was found to positively regulate the expression of members of the ABA-response pathway (ABI1, ABI5, and RD29A) leading to increased resistance to drought and salinity treatments. Furthermore, HD2D expression delayed flowering by positively regulating FLC expression. Using bimolecular fluorescence complementation, the HD2D protein ...


Characterization And Structure Of A Zn2+ And [2fe-2s]-Containing Copper Chaperone From Archaeoglobus Fulgidus, Matthew Sazinsky, Benjamin Lemoine, Maria Orofino, Roman Davydov, Krisztina Bencze, Timothy Stemmler, Brian Hoffman, José Argüello, Amy Rosenzweig Dec 2015

Characterization And Structure Of A Zn2+ And [2fe-2s]-Containing Copper Chaperone From Archaeoglobus Fulgidus, Matthew Sazinsky, Benjamin Lemoine, Maria Orofino, Roman Davydov, Krisztina Bencze, Timothy Stemmler, Brian Hoffman, José Argüello, Amy Rosenzweig

José M. Argüello

Bacterial CopZ proteins deliver copper to P1B-type Cu+-ATPases that are homologous to the human Wilson and Menkes disease proteins. The genome of the hyperthermophile Archaeoglobus fulgidus encodes a putative CopZ copper chaperone that contains an unusual cysteine rich N-terminal domain of 130 amino acids in addition to a C-terminal copper-binding domain with a conserved CXXC motif. The N-terminal domain (CopZ-NT) is homologous to proteins found only in extremophiles and is the only such protein that is fused to a copper chaperone. Surprisingly, optical, electron paramagnetic resonance, and X-ray absorption spectroscopic data indicate the presence of a [2Fe-2S] cluster in ...


A 4d View On Mrna, Carlas Smith, Li-Chun Tu, David Grünwald Dec 2015

A 4d View On Mrna, Carlas Smith, Li-Chun Tu, David Grünwald

David Grünwald

Imaging single molecules in live cells in 4+ D (space, time and colors) is crucial for studying various biological processes, especially for observing the behavior of RNA molecules within the nuclear landscape [1]. RNA molecules are known to serve a multitude of tasks such as being templates for protein translation or to act as enzymes for regulating countless reactions in the nucleus [1]. Studying RNA kinetics in living cells can provide new information on RNA function or even human diseases, for instance caused by viruses such as the human immunodeficiency virus (HIV) [2]. A challenge to imaging nuclear RNA function ...


Single-Molecule Imaging Reveals That Argonaute Re-Shapes The Properties Of Its Nucleic Acid Guides: A Dissertation, William E. Salomon Dec 2015

Single-Molecule Imaging Reveals That Argonaute Re-Shapes The Properties Of Its Nucleic Acid Guides: A Dissertation, William E. Salomon

GSBS Dissertations and Theses

Small RNA silencing pathways regulate development, viral defense, and genomic integrity in all kingdoms of life. An Argonaute (Ago) protein, guided by a tightly bound, small RNA or DNA, lies at the core of these pathways. Argonaute uses its small RNA or DNA to find its target sequences, which it either cleaves or stably binds, acting as a binding scaffold for other proteins. We used Co-localization Single-Molecule Spectroscopy (CoSMoS) to analyze target binding and cleavage by Ago and its guide. We find that both eukaryotic and prokaryotic Argonaute proteins re-shape the fundamental properties of RNA:RNA, RNA:DNA, and DNA ...


Dynamical Features Of The Plasmodium Falciparum Ribosome During Translation, Ming Sun, Wen Li, Karin Blomqvist, Sanchaita Das, Yaser Hashem, Jeffrey D. Dvorin, Joachim Frank Dec 2015

Dynamical Features Of The Plasmodium Falciparum Ribosome During Translation, Ming Sun, Wen Li, Karin Blomqvist, Sanchaita Das, Yaser Hashem, Jeffrey D. Dvorin, Joachim Frank

Open Access Articles

Plasmodium falciparum, the mosquito-transmitted Apicomplexan parasite, causes the most severe form of human malaria. In the asexual blood-stage, the parasite resides within erythrocytes where it proliferates, multiplies and finally spreads to new erythrocytes. Development of drugs targeting the ribosome, the site of protein synthesis, requires specific knowledge of its structure and work cycle, and, critically, the ways they differ from those in the human host. Here, we present five cryo-electron microscopy (cryo-EM) reconstructions of ribosomes purified from P. falciparum blood-stage schizonts at sub-nanometer resolution. Atomic models were built from these density maps by flexible fitting. Significantly, our study has taken ...


Homozygous Knockout Of The Piezo1 Gene In The Zebrafish Is Not Associated With Anemia, Boris E. Shmukler, Nicholas C. Huston, Jonathan N. Thon, Chih-Wen Ni, George Kourkoulis, Nathan D. Lawson, Barry H. Paw, Seth L. Alper Dec 2015

Homozygous Knockout Of The Piezo1 Gene In The Zebrafish Is Not Associated With Anemia, Boris E. Shmukler, Nicholas C. Huston, Jonathan N. Thon, Chih-Wen Ni, George Kourkoulis, Nathan D. Lawson, Barry H. Paw, Seth L. Alper

Molecular, Cell and Cancer Biology Publications

We have now examined the erythroid phenotype in this zebrafish strain carrying a ZFN genomic knockout of piezo1. Genotyping was performed as previously described. In contrast to the anemic phenotype observed in zebrafish subjected to morpholino knockdown of piezo, the genomic ZFN knockout of piezo1 did not segregate either with anemia in the 3-dpf embryo or with dysmorphic erythrocyte morphology in the adult fish.


Preventing Thymus Involution In K5.Cyclin D1 Transgenic Mice Sustains The Naïve T Cell Compartment With Age, Michelle L. Bolner Dec 2015

Preventing Thymus Involution In K5.Cyclin D1 Transgenic Mice Sustains The Naïve T Cell Compartment With Age, Michelle L. Bolner

UT GSBS Dissertations and Theses (Open Access)

The thymus maintains T cell receptor (TCR) repertoire diversity through perpetual release of self-MHC restricted naive T cells. However, thymus involution during the aging process reduces naïve T cell output, leading to defective immune responsiveness to newly encountered antigens. We have found that early thymus involution precipitates the age-associated shift favoring memory T cell dominancy in young control mice. Furthermore, we have shown that age-related thymus involution is prevented in mice expressing a keratin 5 promoter-driven Cyclin D1 (K5.D1) transgene in thymic epithelial cells (TECs). Thymopoiesis occurs normally in K5.D1 transgenic thymi and sustains T cell output to ...


Molecular Regulation Of Vascular Calcification In Murine Models Of Atherosclerosis, Shanshan Gao Dec 2015

Molecular Regulation Of Vascular Calcification In Murine Models Of Atherosclerosis, Shanshan Gao

UT GSBS Dissertations and Theses (Open Access)

Background: Calcification occurs often in the atherosclerotic lesions of patients with coronary heart disease and animals with hypercholesterolemia, such as apolipoprotein-E deficient (ApoE-/-) mice. However, the mechanism(s) underlying the development of calcification in atherosclerosis remains unclear. ApoE acts as a lipid transporter, but also has been recognized as a potential regulator of osteogenesis. Little information is available as to whether ApoE has any direct impact on osteogenesis and calcification in vascular smooth muscle cells (VSMC). Several signal transduction pathways play a role in regulation of calcification, including the Wnt/β-catenin system and potentially GTAP, an ubiquitin-conjugating enzyme responsible for ...


Blackberry Virosome: A Micro And Macro Approach, Archana Khadgi Dec 2015

Blackberry Virosome: A Micro And Macro Approach, Archana Khadgi

Theses and Dissertations

Viruses pose a major concern for blackberry production around the world with more than 40 species known to infect the crop. Virus complexes have been identified recently as the major cause of plant decline with blackberry yellow vein disease (BYVD) being the most important disease of the crop in the Southern United States. The objective of this research was to study the blackberry virosome in both the macro and micro scale. The large scale approach involves identification of the major viruses known to be associated with BYVD in the Southern United States as well as the identification of other viruses ...


Autophagy And Its Potential Role In Stress And Feed Efficiency Using Avian Lines, Alissa Laura Piekarski Dec 2015

Autophagy And Its Potential Role In Stress And Feed Efficiency Using Avian Lines, Alissa Laura Piekarski

Theses and Dissertations

Autophagy is a highly conserved cellular mechanism that is responsible for the degradation and recycling of damaged organelles. Recently, autophagy has been involved in critical roles during overall development of the organism and degradation of damaged cellular components. This pathway has witnessed dramatic growth in the last few years and has been extensively studied in yeast and mammals, however, there is a paucity of information in avian (non-mammalian) species. First, we characterized genes involved in the autophagy pathway in male and female Jungle Fowl to determine gender and tissue specific differences. Secondly, tissue and genotype differences in Japanese quail selected ...


Transcriptomics Of Chicken Primordial Germ Cells, Nhung Thi Nguyen Dec 2015

Transcriptomics Of Chicken Primordial Germ Cells, Nhung Thi Nguyen

Theses and Dissertations

Chicken primordial germ cells (PGCs) are derived from extraembryonic tissue of the embryo and first appear at stage X of development. They enter the bloodstream and migrate to the genital ridge, unite with somatic tissue to form a developing gonad, and then differentiate to sperm or ova (Fujimoto et al., 1976). Understanding molecular features of both male and female PGCs not only clarify the differentiation mechanism of such cells toward different germ lines, but will also help in selecting for highly productive types of commercial chicken. Most previous studies focused on the location of PGCs (Eyal-Giladi et al., 1981; Swift ...


Transport Mechanisms For Human Fecal Indicator Bacteria In An Urban Stormwater Basin In Southeastern Wisconsin, Chelsea M. Corson Dec 2015

Transport Mechanisms For Human Fecal Indicator Bacteria In An Urban Stormwater Basin In Southeastern Wisconsin, Chelsea M. Corson

Theses and Dissertations

Discharge of stormwater runoff to receiving waters is a known source of human pathogens; however the primary mechanisms by which these pathogens enter the stormwater system have yet to be quantified. This study builds upon and utilizes prior research findings in an attempt to explain the influence of the age of the pipes within stormwater and sanitary conveyance systems, rainfall and hydrogeological characteristics, and select infrastructure variables that contribute to the observed contamination of an urban stormwater basin in Southeastern Wisconsin.

Over the course of approximately two years from 2012 to 2014, a total of 260 samples from 22 stormwater ...


Optimizing A Luciferase-Based Tool For Studying The Effects Of Fatty Acid Desaturase 7 On Singlet Oxygen Accumulation In Arabidopsis Thaliana, Abeer Muhammedali Alnasrawi Dec 2015

Optimizing A Luciferase-Based Tool For Studying The Effects Of Fatty Acid Desaturase 7 On Singlet Oxygen Accumulation In Arabidopsis Thaliana, Abeer Muhammedali Alnasrawi

Theses and Dissertations

In plants, reactive oxygen species (ROS) are generated as a byproduct of normal metabolism, as well as in response to adverse conditions such as light stress, extreme temperatures, and exposure to pests and pathogens. Singlet oxygen (1O2) is a ROS that is formed during photosynthesis in photosystem II (PSII) of the chloroplasts. Levels of 1O2 and other ROS are tightly controlled in healthy plants, but some studies suggest that levels of fatty acid desaturase (FAD) activity in Arabidopsis thaliana can influence constitutive and/or stress-responsive ROS accumulation. In this study, a luciferase-based reporter gene that is selectively stimulated by 1O2 ...


High Yield Expression Of Recombinant Human Proteins With The Transient Transfection Of Hek293 Cells In Suspension, Ganesh P. Subedi, Roy W. Johnson, Heather A. Moniz, Kelley W. Moreman, Adam W. Barb Dec 2015

High Yield Expression Of Recombinant Human Proteins With The Transient Transfection Of Hek293 Cells In Suspension, Ganesh P. Subedi, Roy W. Johnson, Heather A. Moniz, Kelley W. Moreman, Adam W. Barb

Biochemistry, Biophysics and Molecular Biology Publications

The art of producing recombinant proteins with complex post-translational modifications represents a major challenge for studies of structure and function. The rapid establishment and high recovery from transiently-transfected mammalian cell lines addresses this barrier and is an effective means of expressing proteins that are naturally channeled through the ER and Golgi-mediated secretory pathway. Here is one protocol for protein expression using the human HEK293F and HEK293S cell lines transfected with a mammalian expression vector designed for high protein yields. The applicability of this system is demonstrated using three representative glycoproteins that expressed with yields between 95-120 mg of purified protein ...


Development And Validation Of A Novel In Vitro Model For The Assessment Of Heterocellular Interactions Mediated By Connexin43, Emily Ongstad Dec 2015

Development And Validation Of A Novel In Vitro Model For The Assessment Of Heterocellular Interactions Mediated By Connexin43, Emily Ongstad

All Dissertations

The injury border zone (IBZ), a region of transitional tissue between intact myocardium and the ischemic area, is often the site of lethal reentrant arrhythmia generation in post-myocardial infarction (MI) patients. Disruption to normal connexin43 (Cx43) localization at the intercalated disc (ID), separation of myocytes by activated fibroblasts and deposited scar tissue are thought to be factors that render the IBZ a pro-arrhythmic substrate, though there is a current need to better understand these changes so directed therapies can be developed. There are no clinically available therapies focused on the mechanistic changes in the IBZ. Additionally, generation of new compounds ...


Arsenic Inhibits P19 Stem Cell Differentiation By Altering Microrna Expression And Repressing The Sonic Hedgehog Signaling Pathway, Jui Tung Liu Dec 2015

Arsenic Inhibits P19 Stem Cell Differentiation By Altering Microrna Expression And Repressing The Sonic Hedgehog Signaling Pathway, Jui Tung Liu

All Dissertations

Arsenic is a naturally-occurring toxicant that exists in bedrock and can be leached into ground water. Humans can be exposed to arsenic via contaminated drinking water, fruit, rice or crops. Epidemiological studies have shown that arsenic is a developmental toxicant, and in utero exposure reduces IQ scores, verbal learning ability, decreases long term memory, and increases the likelihood of dying from a neurological disorder. Arsenic can also reduce birth weight, weight gain, and muscle function after an in utero exposure. Although the mechanism behind these physiological changes is not known, in vitro studies have shown that arsenic can reduce muscle ...


Hydrophobically Modified Sirnas Silence Huntingtin Mrna In Primary Neurons And Mouse Brain, Julia F. Alterman, Lauren M. Hall, Andrew H. Coles, Matthew R. Hassler, Marie C. Didiot, Kathryn O. Chase, Jasmin Abraham, Emily Sottosanti, Emily S. Johnson, Ellen Sapp, Maire F. Osborn, Marian Difiglia, Neil Aronin, Anastasia Khvorova Dec 2015

Hydrophobically Modified Sirnas Silence Huntingtin Mrna In Primary Neurons And Mouse Brain, Julia F. Alterman, Lauren M. Hall, Andrew H. Coles, Matthew R. Hassler, Marie C. Didiot, Kathryn O. Chase, Jasmin Abraham, Emily Sottosanti, Emily S. Johnson, Ellen Sapp, Maire F. Osborn, Marian Difiglia, Neil Aronin, Anastasia Khvorova

RNA Therapeutics Institute Publications

Applications of RNA interference for neuroscience research have been limited by a lack of simple and efficient methods to deliver oligonucleotides to primary neurons in culture and to the brain. Here, we show that primary neurons rapidly internalize hydrophobically modified siRNAs (hsiRNAs) added directly to the culture medium without lipid formulation. We identify functional hsiRNAs targeting the mRNA of huntingtin, the mutation of which is responsible for Huntington's disease, and show that direct uptake in neurons induces potent and specific silencing in vitro. Moreover, a single injection of unformulated hsiRNA into mouse brain silences Htt mRNA with minimal neuronal ...


Characterization Of Sbip68: A Putative Tobacco Glucosyltransferase Protein And Its Role In Plant Defense Mechanisms, Abdulkareem O. Odesina Dec 2015

Characterization Of Sbip68: A Putative Tobacco Glucosyltransferase Protein And Its Role In Plant Defense Mechanisms, Abdulkareem O. Odesina

Electronic Theses and Dissertations

Plant secondary metabolites are essential for normal growth and development in plants ultimately affecting crop yield. They play roles ranging from appearance of the plants to defending against pathogen attack and herbivory. They have been used by humans for medicinal and recreational purposes amongst others. Glycosyltransferases catalyze the transfer of sugars from donor substrates to acceptors. Glucosyltransferases are a specific type of glycosyltransferases known to transfer glucose molecules from a glucose donor to a glucose acceptor (aglycone) producing the corresponding glucose secondary metabolite or glycone, in this case glucosides. It was hypothesized that SBIP68, a tobacco putative glucosyltransferase-like protein glucosylated ...


Co-Treatment With Conjugated Linoleic Acid And Nitrite Modulates Mitochondrial Respiration And Electron Transport Chain Activity In Vivo And Attenuates Mitochondrial Dysfunction During Cardiac Injury., Patrick Van Hoose Dec 2015

Co-Treatment With Conjugated Linoleic Acid And Nitrite Modulates Mitochondrial Respiration And Electron Transport Chain Activity In Vivo And Attenuates Mitochondrial Dysfunction During Cardiac Injury., Patrick Van Hoose

Electronic Theses and Dissertations

Cardiovascular disease and subsequent complications, such as myocardial infarction (MI), is the leading cause of death within the United States. Clinical intervention to reduce cardiac damage following myocardial ischemia is limited. Polyunsaturated fatty acids have been linked to an overall beneficial effect on cardiovascular health and function. Conjugated linoleic acid (cLA) is an 18:2 unsaturated fatty acid found within the diet in ruminant meat and dairy products. The cis-9 trans-11 isomer of cLA is the most prominent isomer within the diet and cLA has been linked to favorable outcomes in numerous disease states. The mechanism mediating the effects of ...


Environmental Controls On The Diversity And Distribution Of Endosymbionts Associated With Phacoides Pectinatus (Bivalvia: Lucinidae) From Shallow Mangrove And Seagrass Sediments, St. Lucie County, Florida, Thomas Walters Doty Dec 2015

Environmental Controls On The Diversity And Distribution Of Endosymbionts Associated With Phacoides Pectinatus (Bivalvia: Lucinidae) From Shallow Mangrove And Seagrass Sediments, St. Lucie County, Florida, Thomas Walters Doty

Masters Theses

Lucinid bivalves are capable of colonizing traditionally inhospitable shallow marine sediments due to metabolic functions of bacterial endosymbionts located within their gills. Because lucinids can often be the dominant sediment infauna, defining their roles in sediment and pore fluid geochemical cycling is necessary to address concerns related to changes in coastal biological diversity and to understanding the sensitivity of threatened coastal ecosystems over time. However, there has been limited research done to understand the diversity and distribution of many lucinid chemosymbiotic systems. Therefore, the goals of this thesis were to evaluate the distribution of Phacoides pectinatus and its endosymbiont communities ...


In Vivo Periodical Monitoring Of Immune Cell Infiltration In Response To Feathers And Intramuscular Injection Of Ionps Using The Pulp (Dermis) Of Growing Feathers As Test Site Tissue In Chickens, Olfat Taleb Alaamri Dec 2015

In Vivo Periodical Monitoring Of Immune Cell Infiltration In Response To Feathers And Intramuscular Injection Of Ionps Using The Pulp (Dermis) Of Growing Feathers As Test Site Tissue In Chickens, Olfat Taleb Alaamri

Theses and Dissertations

The applications of nanoparticles are growing, but little is known about their interactions with the immune system as most studies did not use suitable in vivo test systems. The purpose of these studies was to investigate the utility of chicken growing feathers as an in vivo test site for iron oxide nanoparticle (IONP) interactions with the immune system. The first objective of this study was to monitor leukocyte infiltration into the growing feather pulp upon the administration of IONP and IO-mIgG preparations. The second objective was to test the utility of IONPs as vaccine adjuvants by monitoring primary and memory ...