Life Sciences Commons^™

Thyroid Function And Perfluoroalkyl Acids In Children Living Near A Chemical Plant, Maria-Jose Lopez-Espinosa, Debapriya Mondal, Ben Armstrong, Michael S. Bloom, Tony Fletcher

Environmental Health Sciences Faculty Scholarship

Background: Animal studies suggest that some perfluoroalkyl acids (PFAAs), including perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA) may impair thyroid function. Epidemiological findings, mostly related to adults, are inconsistent.

Objectives: We investigated whether concentrations of PFAAs were associated with thyroid function among 10,725 children (1–17 years of age) living near a Teflon manufacturing facility in the Mid-Ohio Valley (USA).

Methods: Serum levels of thyroid-stimulating hormone (TSH), total thyroxine (TT4), and PFAAs were measured during 2005–2006, and information on diagnosed thyroid disease was collected by questionnaire. Modeled in utero PFOA concentrations were based on historical information on PFOA releases, …

Probing The T-Box Riboswitch: A Novel, High-Throughput Transcription Reporter Assay Using A Fluorophore-Binding Aptamer, Nishtha Modi

Biological Sciences

In most Gram-positive bacteria, including important pathogens, expression of many aminoacyl tRNA synthetase (aaRS) genes is controlled by the tRNA substrate specific to each of these enzymes. This riboswitch regulatory mechanism is unique to Gram-positive bacteria and because correct and efficient aminoacylation of tRNAs is essential to an organism’s viability, it is an ideal target for the development of new antibiotics. The 5’-untranslated region (5’UTR) of the aaRS mRNA adopts a conformation that determines whether readthrough or termination of transcription occurs by interacting with unacylated or acylated tRNA, respectively. Our goal is to uncover a new class of small molecules …

The Senescence-Associated Secretory Phenotype (Sasp) And Redox-Dependent Invasion Of Metastatic Cancer Cells, Brooke A. Pati

Biological Sciences

Throughout your lifetime renewable tissues and those which are exposed to prolonged inflammation experience an accumulation of senescent cells. These cells have previously been shown to acquire the senescence-associated secretory phenotype (SASP) that promotes proliferation and tumorigenesis of epithelial cells, thus increasing the invasive ability of tumor cells (1). SASP is characterized by an upregulation in mRNA levels of a number of secretory factors, such as growth factors, cytokines, and chemokines. It has been shown that lifetime exposure to oxidative stress can influence cell cytoskeleton reorganization and influence aging processes (2). In addition matrix metalloproteinases are key SASP factors that …

Micropatterned Electrospun Nanofibrous Substrates As Scaffolds For Engineered Salivary Glands, David Alexander Soscia

Legacy Theses & Dissertations (2009 - 2024)

The salivary gland is a complex organ exhibiting a branching, 3-dimensional structure made up of acinar (saliva-producing), and ductal (saliva transporting and modifying) epithelial cells. The high surface area of the gland allows it to efficiently provide the mouth with saliva, maintaining oral cleanliness and comfort. Salivary gland hypofunction, a significant clinical problem often caused by the autoimmune disease Sjögren's syndrome or head and neck radiation for cancer patients, affects millions of Americans and is characterized by a loss of function of salivary gland acinar cells. Chronic xerostomia, or dry mouth, arises as a result of salivary gland hypofunction and …

Identification Of Trophic And Transcriptional Requirements For Human Embryonic Stem Cell Culture And Guided Neural Differentiation, Nicolas Edward Tokas

Legacy Theses & Dissertations (2009 - 2024)

Translational biomedical research holds potential for the development of novel therapeutics for the treatment of injury, illness or disability. To better understand intrinsic cellular and molecular biology, human embryonic stem cells (hESCs) can be used as a tool. hESCs are pluripotent with the abilities to be held in a self-renewal state or become induced to a desired germ layer then to be later directed through differentiation.

Intra And Interhost Dynamics Shaping Arbovirus Adaptation And Evolution, Alexander T. Ciota

Legacy Theses & Dissertations (2009 - 2024)

Arthropod-borne viruses (arboviruses), which are predominately mosquito-borne and almost exclusively RNA viruses, are maintained in nature in complex transmission cycles involving blood sucking invertebrates and vertebrate hosts. Although over 120 arboviruses are human pathogens responsible for causing a significant and expanding global health burden, a detailed understanding of the complex interactions between these pathogens and their hosts, particularly invertebrate hosts, is lacking. Defining these interactions is necessary if we are to understand the selective pressures and, therefore, evolutionary, adaptive, and epidemiological potential of arboviruses. This requires experimental infection and evolution studies, particularly in vivo, with natural hosts. The results presented …

A Study Of The Effects Of Inosine Incorporation Into Dna Due To Defects In Purine Biosynthesis In Escherichia Coli, Jonathan Spence Church

Legacy Theses & Dissertations (2009 - 2024)

Deamination of purine bases can result in the formation of xanthine and hypoxanthine which can be miscoding and mutagenic in DNA. There are several mechanisms for the introduction of deaminated bases into DNA including simple hydrolysis, nitrosative chemistry and through the action of deaminase enzymes. A fourth method was recently presented which describes how deaminated purines can be incorporated into DNA due to defects in purine biosynthesis. Using fluctuation analysis, spontaneous mutation rates were studied in bacterial mutants that were deficient in specific genes involved in purine biosynthesis and dNTP precursor pool maintenance, including purA (adenylosuccinate synthetase), guaA (GMP synthetase), …

Habitat Associations And Occupancy Modeling Of Marsh Birds In The Hudson Valley Region Of Eastern New York, Lauren Jorgensen

Legacy Theses & Dissertations (2009 - 2024)

Populations of many North American marsh birds have declined over the past few decades, a trend commensurate with declines in wetland habitat area. Substantial declines in populations of breeding marsh bird species in New York State are associated with declines in wetland habitat area due to urbanization. The objective of this study was to examine what habitat and landscape features increase the probability of occupancy for nine target marsh bird species in New York State. This research was conducted in the Hudson River Valley region of Eastern New York, a region which is characterized by varied topography and geology, a …

Virus Capsids As Nanoscale Delivery Vessels Of Photoactive Compounds For Site-Specific Photodynamic Therapy, Brian Alexander Cohen

Legacy Theses & Dissertations (2009 - 2024)

The research presented in this work details the use of a viral capsid as an addressable delivery vessel of photoactive compounds for use in photodynamic therapy. Photodynamic therapy is a treatment that involves the interaction of light with a photosensitizing molecule to create singlet oxygen, a reactive oxygen species. Overproduction of singlet oxygen in cells can cause oxidative damage leading to cytotoxicity and eventually cell death. Challenges with the current generation of FDA-approved photosensitizers for photodynamic therapy primarily stem from their lack of tissue specificity. This work describes the packaging of photoactive cationic porphyrins inside the MS2 bacteriophage capsid, followed …

Characterization Of Postsynaptic Calcium(Ii) Signals And Their Role In Synaptic Regulation At The Drosophila Larval Neuromuscular Junction, Sunil Ashok Desai

Legacy Theses & Dissertations (2009 - 2024)

Postsynaptic [Ca2+]i has been proposed to play an important role in both synaptic plasticity and synaptic homeostasis. Postsynaptic Ca2+ signals appear to regulate synaptic transmission at the Drosophila larval NMJ; however, they have not been characterized at a NMJ. We were interested in examining the postsynaptic Ca2+ signals in this system and determining its influence on synaptic strength. The muscle Ca2+ transients were recorded by injecting the muscle fibers with Ca2+ indicators; discrete postsynaptic Ca2+ transients were observed along the NMJ during evoked and spontaneous transmitter release. The magnitude of the Ca2+ signals was correlated with synaptic efficacy, terminals producing …

Prenatal Participation In Wic : Impact On Breastfeeding Initiation And Duration And On Infant Weight Gain, Lynn S. Edmunds

Legacy Theses & Dissertations (2009 - 2024)

Background: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is one of the most studied federal food assistance programs. However, few studies have examined the association between maternal WIC participation and breastfeeding or weight gain during infancy. Prenatal WIC participation provides an important widow of influence on birth outcomes but also on early life risk factors for chronic disease. This study utilizes a cohort of WIC enrolled infants to assess the added effect of prenatal exposure to WIC on two specific outcomes - breastfeeding initiation and duration and rate of infant weight gain.

The C. Elegans Rna-Binding Protein Gld-1 Recognizes Sequence, Structure And Context Information To Repress Translation Of Its Mrna Targets, Jung Hoon Doh

Legacy Theses & Dissertations (2009 - 2024)

Considering the general suppression of transcription during late oogenesis and early embryo development, post-transcriptional control of maternal mRNAs by RNA binding proteins emerges as an important mechanism in controlling late oogenesis and early embryo development. The C. elegans germline offers an ideal system to understand such processes. GLD-1 (GermLine Development defective) is a maxi-KH motif containing RNA binding protein, which controls many different stages during the C. elegans germline development from decision over germ cell proliferation vs. meiosis entry to production of mature gametes, suggesting that GLD-1 likely controls many mRNA targets. gld-1 mutants have variable germline defects, the major …

Dna Repair Fidelity And Cancer : Structural And Kinetic Insights From Dna Polymerase Beta Mutator Variants, Chelsea Lynne Gridley

Legacy Theses & Dissertations (2009 - 2024)

DNA polymerases are essential for genome replication and DNA repair in all living organisms. Precise DNA replication is critical for the preservation of genomic stability. Any insult, endogenous/exogenous, to cellular DNA requires properly functioning repair polymerases. In eukaryotes, DNA polymerase beta, a small enzyme (39 kDa), plays an important role in DNA repair during the base excision repair pathway. Pol beta catalyzes the incorporation of nucleotides in small stretches (1-6 nucleotides) of damaged double-stranded DNA. Should gap-filling synthesis by pol beta be compromised, mutations in genomic DNA accumulate, which are frequently linked to human diseases, including cancers. For this reason, …

Expression And Purification Of The K2p Family Of Ion Channels, Drew Barber

Legacy Theses & Dissertations (2009 - 2024)

The KCNK (two-pore-domain K+ channel) family of potassium channels are the most widely expressed potassium channels in mammals. They are expressed in numerous organs including the brain, heart, adrenal glands, and kidneys. There are fifteen members of this family which can be further divided into six sub groups. These proteins can act as leak channels, setting the rest membrane potential of electrically excitable cells. Due to their function as modulators of excitability these proteins are under control from numerous different chemical and physical signals which include oxygen tension, pH, lipids, mechanical stretch, and neurotransmitters. These channels are not as well …

Sirtuin 6 : A Review Of Biological Affects And Potential Therapeutic Properties, Jade Beauharnois

Legacy Theses & Dissertations (2009 - 2024)

ABSTRACT: Sirtuins, possessing either histone deacetylase or mono-ribosyltransferase activity, regulate important biological pathways in bacteria, archaea and eukaryotes. The term Sir2 comes from the yeast 'silent mating-type information regulation 2' gene, a gene directing cellular regulation in yeast. Sirtuins have been implicated in aging, regulation of transcription, apoptosis and stress resistance, in addition to energy efficiency and metabolism. In mammals, a variety of sirtuin family members are genetically encoded to include sirtuins 1-7 (SIRT1-SIRT7). SIRT6 is a human sirtuin of interest in a variety of research areas, influencing the genomic instability, metabolic defects and degenerative pathologies associated with aging. Until …

Stewards Of The Land : Demonstrations Of Agricultural Authenticity In Columbia County, Ny, Jaclyn Rose Bruntfield

Legacy Theses & Dissertations (2009 - 2024)

The origins of food in the U.S. have come under close public scrutiny in recent years. An increasing number of farmers markets, certified organic products, and Community Supported Agriculture programs indicate that Americans are seeking out alternatives to the mainstream food system. The industrialization of food production in the post-World War II era, while providing larger amounts of inexpensive food than ever before, has arguably compromised people's relationships with food. While farming was once a common way of life in the U.S., today only one percent of Americans identify farming as their primary occupation.

Expression Of Suppressor Of Cytokine Signaling 2 (Socs2) During Optic Nerve Regeneration In Xenopus Laevis, Rupa Priscilla Choudhary

Legacy Theses & Dissertations (2009 - 2024)

The optic nerve and other central nervous system (CNS) axons tend to lose their capacity to regenerate following an injury in adult amniotes, but these axons are able to regenerate throughout life in anamniotes. The long-term goal of my study is to identify molecular mechanisms responsible for the retention of this regenerative capacity. Specifically, I will examine the role of the gene Suppressor of Cytokine Signaling 2 (SOCS2) in the successful regeneration of retinal ganglion cell (RGC) axons of the South African claw-toed frog, Xenopus laevis, after injury.

Experimental Studies Of The Multitrophic Effects Of Anti-Herbivore Defense In Three Pine Barrens Shrub Species, Elizabeth R. Coffey

Legacy Theses & Dissertations (2009 - 2024)

Plants produce numerous chemical defense compounds in response to herbivory. Induced chemical defenses potentially influence soil dynamics by changing the nutrient ratio of the leaves, which are seasonally shed and contribute to the soil, or by affecting the detritus community through leaching of chemicals in the root zone. Manual clipping was utilized in this study to induce chemical compounds with the goal of examining the secondary effects of induced plant defenses. I removed 25% of the mass of fifteen plants of three different plant species in the Albany Pine Bush annually for two consecutive years. I then compared the soil …

Detection And Epidemiological Patterns Of Drug Resistance Mutations In Nys Plasmodium Falciparum Clinical Malaria Specimens, Jennifer L. Conaway

Legacy Theses & Dissertations (2009 - 2024)

Plasmodium falciparum is a human-infective parasite that causes the most severe form of malaria. Resistance to a wide spectrum of antimalarials has been documented in this species, and single strains may be resistant to several drugs. A new technology, pyrosequencing, has been shown to be useful for the rapid detection of SNPs involved in drug resistance. It can be used in a clinical setting and readily detects new mutants, which frequently appear in this species due to strong selection for antimalarial resistance. In this study, a pyrosequencing protocol was developed to identify mutations in the Plasmodium falciparum genes Pfcrt, Pfdhps, …

Developing A Toolkit To Study The Role Of Inteins In Mycobacterial Biology, Rupsa Dey

Legacy Theses & Dissertations (2009 - 2024)

Tuberculosis, caused by Mycobacterium tuberculosis, is one of the most widespread and highly contagious diseases in the world today. This disease affects people from all walks of life and has a devastating effect on immune compromised individuals. Another concerning fact is the emergence of multiple drug resistant and extreme drug resistant strains of the bacilli that has made treatment very difficult. Thus it has become imperative that every avenue should be explored to fight and eradicate this disease. One such unexplored avenue is the role of inteins in mycobacterial biology. Inteins are intervening sequences found in conserved regions of a …

Ultraviolet Resonance Raman Spectroscopy For Characterization Of Rna Structure And Thermodynamics, Joseph Dustin Handen

Legacy Theses & Dissertations (2009 - 2024)

Raman spectroscopy is a technique well suited for the study of biological molecules such as proteins, peptides, or RNAs. By utilizing an ultraviolet resonance Raman (UVRR) instrument, we are afforded a tremendous increase in sensitivity because of resonance enhancement. Additionally, this technique does not require any labeling. Moreover, this technique is better suited for studying biological systems than infrared absorption due to reduced interference from water. In this study, we apply techniques we have developed for the study of protein and peptide fibrillation to a model RNA homodimer. We demonstrate that UVRR spectroscopy is uniquely suited to monitoring the free …

Inhibition Of Glutamate Receptors By Constructing Bipartite Rna Aptamers, Jeffrey Hebert

Legacy Theses & Dissertations (2009 - 2024)

The relationship of excessive activity of AMPA-type glutamate receptors, and cell death, has long provided researchers a means of investigating neurodegenerative disorders, such as Parkinson's Disease (PD) and amyotrophic lateral sclerosis (ALS). Inhibitors of AMPA receptor channels, including chemical and nucleic acid molecules such as RNA aptamers, have served as potential therapeutic agents and treatment of neurodegenerative disorders. In this study, building bipartite aptamers to enhance inhibitory potency, as compared with a monomeric aptamer of AMPA receptor, is described. An enhanced potency is due, at least in part; to the proximity effect in bipartite structures or binding of a monomeric …

Characterization Of The Calmodulin-Ryanodine Receptor Interaction By Cryo-Electron Microscopy, Xiaojun Huang

Legacy Theses & Dissertations (2009 - 2024)

Ryanodine receptor (RyR) is a key player in excitation-contraction coupling (E-C coupling). Calmodulin (CaM) is one of the important regulatory factors of RyR. Two mammalian RyR isoforms, RyR1 and RyR2, are highly enriched in skeletal and cardiac muscle, respectively. Apo-calmodulin weakly activates RyR1 but inhibits RyR2, whereas Ca2+-calmodulin inhibits both the isoforms. Previous cryo-electron microscopy studies showed distinctly different binding locations on RyR1 for the two states of calmodulin. However, recent studies employing fluorescence resonance energy transfer appeared to challenge these findings. In chapter 1, using cryo-electron microscopy, we have determined that a mutant calmodulin, which is incapable of binding …

Interactions Of The Human Immunodeficiency Virus Type 1 Nucleocapsid Protein With Non-Hiv-Derived Nucleic Acids : Implications For The Viral Replication Cycle, Abhijit Padmakar Jadhav

Legacy Theses & Dissertations (2009 - 2024)

During attempts to develop aptamers that bind to the nucleocapsid protein of HIV-1 (i.e. NCp7) with high affinity, a heretofore unreported property of the protein--the ability to mediate degradation of nucleic acids, was discovered. Using λ DNA as a model nucleic acid system, it was shown that NCp7-mediated degradation of nucleic acids is non-specific, depends on incubation time, the concentration of NCp7, and the presence of divalent and monovalent cations. It was further demonstrated that degradation can be abrogated if NCp7 is pre-incubated with NCp7-inhibitors. Lyophilization of NCp7 can induce irreversible changes in its secondary structure that result in loss …

Antibody Production During Ehrlichial Infection : Development And Specificity Of T Cell-Independent Igm, Derek Daniel Jones

Legacy Theses & Dissertations (2009 - 2024)

Historically, the role for antibodies in mediating protective immunity against intracellular pathogens was thought to be minimal. However, our previous studies demonstrated that antibodies were both necessary and sufficient to establish protective immunity against Ehrlichia muris, a tick-transmitted intracellular bacterium. The identification of a unique population of CD11c-expressing IgM-secreting plasmablasts in the spleen during early infection of mice led to the appreciation that IgM was a critical component of the humoral immune response, and that IgM was required for control of acute ehrlichial infection. Here, we addressed the generation of the IgM-secreting cells, as well as the properties of the …

Association Between Chemical Constituents Of Particulate Matter And Cardiovascular And Respiratory Morbidities In Nys, Rena Jones

Legacy Theses & Dissertations (2009 - 2024)

Improved understanding of health risks from short- and long-term exposure to fine particulate matter (PM_2.5) constituents may explain seasonal and geographic heterogeneity in PM_{2.5-health associations and inform control efforts targeting PM sources. Few studies have examined PM species health effects; most have been limited by their exposure assessments and modeling approaches. The goals of this project were to improve the PM exposure assessment and explore relationships between PM2.5 species and health in acute and chronic contexts.}

Effects Of Lead Exposure On Synaptic Function, Shoily Parveen Khondker

Legacy Theses & Dissertations (2009 - 2024)

Abstract

Seafood Consumption And Use Of Asian Herbal Preparation As A Source Of Exposure To Multiple Trace Elements In The Study Of Metals And Assisted Reproductive Technologies (Smart), Dongsul Kim

Legacy Theses & Dissertations (2009 - 2024)

As, Cd, Cs, Hg, Pb, and Zn may be associated with in vitro fertilization (IVF) outcomes. Seafood and Asian herbal preparations are identified as sources of exposure to these essential and non-essential trace elements in humans. The goal of the study is to assess associations between seafood consumption and the use of Asian herbal preparations and levels of essential and non-essential trace elements in biologic specimens collected from couples undergoing IVF. Fifty-nine couples completing a first IVF cycle at the University of California, San Francisco (UCSF) Center for Reproductive Health were recruited to participate in the Study of Metals and …

Amyloid Fibril Polymorphism : Structure, Supramolecular Chiraliy And Spontaneous Interconversion, Dzmitry Kurouski

Legacy Theses & Dissertations (2009 - 2024)

Specific protein aggregation has been linked to more than 25 severe human maladies including prion, Alzheimer's, and Parkinson's diseases. These important malfunctions are often referred to as 'conformational' disorders and result from the conversion of a normal isoform of a protein into a specific b-sheet rich polymeric amyloid form. This work elaborates a comprehensive characterization of amyloids and dedicated to the investigation of the fibril polymorphism using advanced microscopic tools, such as Atomic Force and Scanning Electron microcopies, together with several vibrational spectroscopy techniques, such as Raman, Infrared and Vibrational Circular Dichroism. A new type of protein folding-aggregation phenomenon, spontaneous …

The Role Of An Rna Binding Protein Hnrnp K During Axon Development And Regeneration In Xenopus Laevis, Yuanyuan Liu

Legacy Theses & Dissertations (2009 - 2024)

Coordinated synthesis and assembly of the cytoskeletal network contribute significantly to morphological changes during axon outgrowth. Previous studies demonstrated that heterogeneous ribonucleoprotein K (hnRNP K), an RNA binding protein, binds to the 3'-untranslated regions of all neurofilament triplet subunits, the most abundant components of the axonal cytoskeleton. These findings raised the hypothesis that hnRNP K post-transcriptionally mediates the coordinated expression of axonal cytoskeletal components. In my thesis, I test this hypothesis during both axonal development and regeneration.