Digital Commons Network^™

Wip1 Phage Specificity For B. Anthracis, Sherry Kan

Student Theses and Dissertations

Bacteriophage-based diagnostics and therapeutics have been recognized as tools to combat bacterial infections for nearly a century. Wip1 is a recently isolated phage that infects Bacillus anthracis, the notorious biothreat pathogen and gram-positive bacterium that causes anthrax disease. The current standard for identifying suspected B. anthracis involves testing for Wγ phage sensitivity. However, studies have shown that the narrow Wip1 host range is even more specific to B. anthracis than that of Wγ, suggesting that Wip1 may be a superior diagnostic tool. Wip1's high specificity to B. anthracis is likely mediated by the initial recognition and binding of the virus …

The Neural Circuit For Behavioral Responses To Pheromone And Social Behavior In Caenorhabditis Elegans, Heeun Jang

Student Theses and Dissertations

Social behavior is a widespread phenomenon across species from microorganisms to humans. Chemical communication using pheromones is particularly interesting for its versatile use in many organisms, and has been studied at both molecular and circuit levels. However, the central issue of how genes and molecular components contribute to neural circuits that eventually lead to complex social behaviors remains unclear. Using the nematode model organism Caenorhabditis elegans, I have examined two behavioral responses to pheromones, pheromone avoidance and pheromoneregulated social aggregation behavior, at genetic and circuit levels. The known C. elegans pheromones are a set of related compounds called ascarosides. Specific …

Exploring Synaptic Vesicle Exocytosis, Pablo Ariel

Student Theses and Dissertations

The strength of a synapse is an important variable that will affect the function of neural circuits. This thesis develops optical techniques to study determinants of presynaptic efficiency. Our methods are largely based on a chimera of a pH-sensitive variant of the green fluorescent protein and the vesicular glutamate transporter. This reporter is incorporated into synaptic vesicles and increases its fluorescence when those vesicles fuse with the presynaptic membrane. Using this reporter, we measure the size of the primed pool of vesicles (n), a privileged subset of synaptic vesicles which are docked at the active zone and can immediately fuse …

Characterization Of The Central Cavity Of A Potassium Channel: Helix Dipoles, Conformational Plasticity And Inhibition, Disan Schold Davis

Student Theses and Dissertations

Potassium channels are important for regulating the flow of potassium ions across semi-permeable cell membranes in an efficient and selective manner. Potassium channels form a conduction pore comprised of a selectivity filter responsible for the strong preference for potassium, and a water-filled central cavity that contributes to rapid conduction by lowering the energy barrier for potassium ions to cross the low dielectric membrane environment. In the high resolution structure of the potassium channel KcsA, a hydrated potassium ion was observed in the central cavity. It was proposed that some electrostatic stabilization for this potassium ion may come from the backbone …

Approaches To Study Small Molecule Inhibitors And Their Targets, Sarah Anne Wacker

Student Theses and Dissertations

Bioactive small molecules are valuable tools to understand and manipulate biological pathways. In order to be effective as either probes for understanding cell biology or as clinical drugs, the small molecule's mechanism of action must be characterized. However, identifying a small molecule's target and characterizing its interaction with that target remain major challenges in the chemical biology field. In this thesis, I describe methods to improve the process of drug target identification and binding site characterization. In order to identify the target of a small molecule, I have developed an approach in which multiple drug resistant clones are isolated and …

Progress Towards Integrated Models Of Hcv Dynamics, Thomas S. Oh

Student Theses and Dissertations

Hepatitis C virus is a small, enveloped positive-strand RNA member of the Flaviviridae and the etiological agent of a global epidemic of chronic hepatitis C. One of the salient features of HCV is a complex regulatory scheme involving numerous viral and cellular components and which may be the key to its striking success in initiating and maintaining decades-long chronic disease in infected individuals. Lacking any known latent or integrated form, HCV must persist through ongoing RNA replication, immune evasion, and infection of naïve cells. HCV is a highly-studied virus, and many details of its life cycle have been worked out; …

Chemical Reporters For Bacterial Pathogenesis And Beyond, Markus Grammel

Student Theses and Dissertations

Microbial infection involves complex and dynamic interplay of host defense and pathogen virulence pathways that requires new methods for mechanistic investigation. Towards this goal, I have developed chemical reporters of nucleic acid and protein synthesis and posttranslational modifications to explore their functions in bacterial pathogenesis as well as basic biological pathways. Initially, I developed amino acid chemical reporters that allow the cell-selective labeling of bacterial proteomes to facilitate the analysis of bacterial protein expression during infection of host cells. These reporters are based on unnatural amino acids that are incorporated into the bacterial proteome instead of methionine or phenylalanine when …

Dissecting Synaptic Vesicle Endocytosis, Moritz Armbruster

Student Theses and Dissertations

Synaptic vesicle endocytosis is critical for ensuring rapid local recycling of synaptic vesicles to enable ongoing neuronal activity. We utilized the sensitivity and robustness of the pHluorin assay of synaptic vesicle recycling to probe the control of endocytosis spatially and in response to varying stimulation conditions. We examined the role of the large GTPases dynamin 1 and dynamin 3 in synaptic vesicle endocytosis; which have been thought to be essential for the fission of budding vesicles from the plasma membrane. Dynamin 1, 3 and 1/3 double knockouts indicated that there is redundant presynaptic function of the proteins. Loss of either …

Variability In Singing And In Song In The Zebra Finch, Cameron Wellock

Student Theses and Dissertations

Variability is a defining feature of the oscine song learning process, reflected in song and in the neural pathways involved in song learning. For the zebra finch, juveniles learning to sing typically exhibit a high degree of vocal variability, and this variability appears to be driven by a key brain nucleus. It has been suggested that this variability is a necessary part of a trial-and-error learning process in which the bird must search for possible improvements to its song. Our work examines the role this variability plays in learning in two ways: through behavioral experiments with juvenile zebra finches, and …

Vocal Handedness: The Emergence Of Lateralization At Fledging, Rudy Bellani

Student Theses and Dissertations

Adult waterslager canaries produce the majority of their song under the control of the left hemisphere/left syringeal half. Unilateral section of the left treacheosyringeal nerve results in near complete loss of song while right denervation affects only a subset of call elements. This strong asymmetry for the production of a learned vocalization is reminiscent of the left hemisphere control for language in humans and provides a potentially powerful animal model to study lateralized behaviors in the vertebrate brain. Earlier work on another songbird, the European chaffinch, Friungilla crebes, suggested that the onset of lateralized vocalizations occured before song learning took …

The Application Of Functional Metagenomics To Natural Products Research, Jeffrey William Craig

Student Theses and Dissertations

The study of bacterial natural products offers important insights into the physiologies and behaviors of individual species of bacteria as well as the contributions of these organisms to complex microbial communities. Such information frequently has important downstream applications in medicine, industry, agriculture, biotechnology, basic sciences and applied microbiology. The majority of bacteria found in nature cannot be cultivated in a laboratory setting, however, leaving a wealth of genetic and chemical diversity unexplored by traditional microbiological methods. Culture-independent approaches for studying diverse microbial populations affords indirect access to these resources. Within the wide array of culture-independent approaches currently in use (collectively …

Structure Function Analysis Of Adenosine Deaminase Acting On Trna (Adat2) From Trypanosoma Brucei, Miller Marshall

Student Theses and Dissertations

tRNA is edited at the wobble position of the anticodon to accommodate the degeneracy of the genetic code. The enzymes responsible for deamination of adenosine 34 to inosine are found in all organisms and in all but a few cases are essential for life. In bacteria the reaction is carried out by the homodimeric adenosine deaminase acting on tRNA (ADAT) and modifies only tRNAarg, whereas in eukarya the enzyme is the ADAT2/3 heterodimer, which performs the same reaction on all tRNA molecules with adenosine at position 34. Despite a similar evolutionary origin, the characteristics of these two enzymes are significantly …

The Expression Of The Zinc Finger Transcription Factor Zdc Defines The Classical Dendritic Cell Lineage, Matthew M. Meredith

Student Theses and Dissertations

Classical dendritic cells (cDCs) are a critical component of the immune system due to their roles in the maintenance of immune tolerance and the induction of adaptive immune responses. However, distinguishing cDCs from other myeloid populations is complicated by the lack of highly specific cDC markers. For example, high expression of the integrin CD11c is used to define cDCs, but this marker is also expressed at lower levels by plasmacytoid dendritic cells, monocyte and macrophage subsets, and some lymphocytes. Similarly, the use of the CD11c promoter to drive the expression of different reporters in cDCs likewise affects these additional populations. …

Structure And Organization Of Nuclear Pore Proteins, Claire Atkinson

Student Theses and Dissertations

The nuclear pore complex (NPC) is a large macromolecular assembly that controls the flow of molecules between the nucleus and the cytoplasm. Elucidating the structure and organization of this complex will be crucial to understanding the mechanism of nucleocytoplasmic transport, but due to its size, the NPC presents a challenge to structure determination. There are electron microscopy (EM) structures of the entire NPC, and high resolution crystal structures of some of the individual components have been solved, but the arrangement of proteins within the overall complex remains unknown. An approach to solving structures of macromolecular complexes is to fit high …

Examining Intracellular Phosphorylation Gradients During Cell Division, Lei Tan

Student Theses and Dissertations

The dynamic cellular reorganization needed for successful mitosis requires spatial regulatory cues. I examine this problem at two different levels. First, I analyze a phosphorylation gradient for substrates of the chromosomal passenger complex (CPC). CPC is a conserved regulator involved in key mitotic events such as chromosome-microtubule attachment and spindle midzone formation. Previously, spatial phosphorylation gradients have been reported for CPC substrates, raising the possibility that CPC-dependent signaling establishes order on the micron-length scale in dividing cells. However, this hypothesis has not been tested, largely because of incomplete characterization of the CPC-dependent phosphorylation dynamics. Here I examine the spatiotemporal dynamics …

Structural And Functional Studies Of Slo K+ Channels: Mechanisms Of Gating By Intracellular Signaling, Manuel D. Leonetti

Student Theses and Dissertations

Eukaryotic K⁺ channels from the SLO family (SLO1, SLO2 and SLO3) provide a link between intracellular signaling and the electrical activity of a cell. The opening and closing (gating) of the three different SLO homologs is controlled by the synergistic action of membrane voltage and specific intracellular cues: Ca²⁺ binding in SLO1, Na⁺ binding in SLO2 and pH increase in SLO3. It is known that intracellular signals activate SLO channels by acting on the large cytoplasmic domains (CTDs) of these proteins, which follows the transmembrane ionconduction pore. However, a molecular description of the mechanisms of intracellular gating …

Micrornas In Breast Cancer Metastasis: Molecular Regulation Of Endothelial Recruitment By Cancer Cells & Regulation Of Metastasis Suppressor Micrornas, Kim J. Png

Student Theses and Dissertations

Metastasis is a highly complex, multi stage process that is clinically daunting, causing the majority of deaths from solid malignancies. A previous study identified three microRNAs that robustly suppresses breast cancer metastasis to lung and bone – miR-126, miR-206 and miR-335. While miR-335 suppressed metastasis through inhibition of cell-autonomous metastatic phenotypes of cell migration and invasion, the role of miR-126 in metastasis remained unknown. Here, endogenous miR-126 is shown to regulate the non-cell autonomous phenotype of endothelial recruitment to metastatic breast cancer cells. Through coordinate targeting of IGFBP2, PITPNC1 and MERTK, miR-126 inhibits endothelial recruitment, which is required for metastatic …

The Dynamic Streptococcus Pyogenes Transcriptome In The Host Cell Environment And Contributions By Phage, Barbara Juncosa

Student Theses and Dissertations

This thesis investigates the transcriptional responses of Streptococcus pyogenes in the pharyngeal environment and characterizes two transcriptional regulators involved in the adaptive response to the host. Furthermore, this thesis explores the potential role of integrated prophage on the streptococcal transcriptome. We are specifically interested in global regulatory systems in group A streptococci and how they impact virulence regulation. With this work, we hoped to identify new regulatory elements involved in the infection process. The first objective of this thesis was to determine the transcriptional shift induced in streptococci upon introduction into the in vitro host environment. Using three time points, …

Using "Designer" Nucleosomes To Study Enzymatic Crosstalk Between Histone Ubiquitylation And Histone Methyltransferases, Sarah J. Whitcomb

Student Theses and Dissertations

It is well established that chromatin is a destination and source for signal transduction affecting all types of DNA metabolism. Histone proteins in particular are extensively post-translationally modified (PTM), and many of these individual modifications have been studied in depth. I have been interested in how the complex repertoire of histone PTMs are co-regulated to generate combinations with meaningful physiological outcomes. One important mechanism is "crosstalk" between pre-existing histone PTMs and enzymes that add or remove subsequent modifications on chromatin. It has been previously shown that H3 lysine 4 methyltransferases involved in transcriptional activation are stimulated and repressed by H2Bub …

Rrna Promoters As Targets For Transcription Factors: Structural And Functional Studies Of Pheri And Card, Joseph S. Osmundson

Student Theses and Dissertations

Transcription, the process of copying information encoded in DNA into RNA, to facilitate the expression of encoded proteins, is a central process in all living organisms. The expression and repression of subsets of genes allows different cell types in an organism to maintain diverse physiological roles and permits individual cells to respond to various environmental stimuli. Transcription in prokaryotic cells is performed by a single macromolecular complex, RNA polymerase. In rapidly growing cells with abundant resources, prokaryotic RNA polymerase is mostly located at ribosomal RNA (rRNA) promoters, actively transcribing the large, structured RNAs required for protein translation. As resources become …

Identification Of A Novel Regulator Of Er Stress-Induced Apoptosis, Genevieve S. Joseph

Student Theses and Dissertations

The survival and development of a multicellular organism is reliant upon proper cell and organelle function, and the tight regulation of cell number. The endoplasmic reticulum (ER) is the cellular compartment where membrane and secretory pathway proteins are folded and modified for transport within or outside of the cell. When the ER becomes overwhelmed by the accumulation of unfolded or misfolded proteins, it enters a state of "ER stress" and the organelle activates the unfolded protein response (UPR) to alleviate the strain. One prominent event during ER stress and the UPR is the Ire1-mediated splicing of unspliced xbp1 (xbp1U) into …

Molecular And Functional Characterization Of Pyramidal Cell Types In The Frontal Cortex Of Mouse Brain, Prerana Shrestha

Student Theses and Dissertations

Mammalian neocortex is the most complex structure in the brain. Considered the seat of executive function, the neocortex subserves diverse cognitive processes such as decision-making, motor planning, sensory discrimination and memory consolidation. The cellular heterogeneity of the neocortex makes it difficult to understand the molecular and cellular substrate of cognition during normal brain function and disease related dysfunction. A deep understanding of the contribution of the neocortex to behavior can best be achieved with reproducible access to genetically defined and functionally coherent cell populations. Using BAC modification strategy, we targeted distinct cell types in the neocortex for expressing effector molecules …

Sample Path Analysis Of Integrate-And-Fire Neurons, Thibaud Taillefumier

Student Theses and Dissertations

Computational neuroscience is concerned with answering two intertwined questions that are based on the assumption that spatio-temporal patterns of spikes form the universal language of the nervous system. First, what function does a specific neural circuitry perform in the elaboration of a behavior? Second, how do neural circuits process behaviorally-relevant information? Non-linear system analysis has proven instrumental in understanding the coding strategies of early neural processing in various sensory modalities. Yet, at higher levels of integration, it fails to help in deciphering the response of assemblies of neurons to complex naturalistic stimuli. If neural activity can be assumed to be …

Mothers' Health And Health Behaviors That Influence Childhod Obesity Maternal Bmi And Infant Feeding Methods, Mohamed Abdullah Alammari

All Graduate Theses, Dissertations, and Other Capstone Projects

The rate of childhood obesity in America continues to climb. Many medical experts believe that childhood obesity can develop as early as prenatal development in the uterus, and infancy. The purpose of this study is to explore the relationships between mothers' health and health behaviors (maternal BMI and infant feeding methods) and childhood obesity. We conducted and analyzed a sample of 307 mothers and their children (307) to examine each mother's maternal BMI and her child or children's BMI. We also examined mothers' feeding methods (bottle vs. breastfeeding).The result of this research did not match with the review of literature. …

Establishment Of Introduced Reptiles Increases With The Presence And Richness Of Native Congeners, Rodrigo Barbosa Ferreira, Karen H. Beard, Stephen L. Peterson, Sharon A. Poessel, Colin M. Callahan

Wildland Resources Faculty Publications

Darwin proposed two contradictory hypotheses to explain the influence of congeners on the outcomes of invasion: the naturalization hypothesis, which predicts a negative relationship between the presence of congeners and invasion success, and the pre-adaptation hypothesis, which predicts a positive relationship between the presence of congeners and invasion success. Studies testing these hypotheses have shown mixed support. We tested these hypotheses using the establishment success of non-native reptiles and congener presence/absence and richness across the globe. Our results demonstrated support for the pre-adaptation hypothesis. We found that globally, both on islands and continents, establishment success was higher in the presence …

Beguiling Religion: The Bifurcations And Biopolitics Of Spirituality And Medicine, M. Therese Lysaught

Institute of Pastoral Studies: Faculty Publications and Other Works

No abstract provided.

Cbdb: The Codon Bias Database, Adam Hilterbrand, Joseph Saelens, Catherine Putonti

Bioinformatics Faculty Publications

Background

In many genomes, a clear preference in the usage of particular codons exists. The mechanisms that induce codon biases remain an open question; studies have attributed codon usage to translational selection, mutational bias and drift. Furthermore, correlations between codon usage within host genomes and their viral pathogens have been observed for a myriad of host-virus systems. As such, numerous studies have investigated codon usage and codon bias in an effort to better understand how species evolve. Numerous metrics have been developed to identify biases in codon usage. In addition, a few data repositories of codon bias data are available, …

Medicine@Yale May 2012 Volume 8, Issue 2, Yale School Of Medicine Office Of Communications

Medicine@Yale - development newsletter

Medicine@Yale : advancing biomedical science, education and health care was a print and online newsletter which published news about academics, research and philanthropy for alumni, donors, faculty, students and the general public. It was initially published 6 times a year and then changed to a quarterly schedule. The first issue came out June/Jul. 2005. The final issue was published in May/June 2022, vol. 17, issue 1. Published by Yale School of Medicine, Office of Communications.

Medicine@Yale September/October 2012 Volume 8, Issue 4, Yale School Of Medicine Office Of Communications

Medicine@Yale - development newsletter

Medicine@Yale : advancing biomedical science, education and health care was a print and online newsletter which published news about academics, research and philanthropy for alumni, donors, faculty, students and the general public. It was initially published 6 times a year and then changed to a quarterly schedule. The first issue came out June/Jul. 2005. The final issue was published in May/June 2022, vol. 17, issue 1. Published by Yale School of Medicine, Office of Communications.

Factors Correlated With Post-Orthodontic Treatment Gingival Enlargement, Erin Arnold

MUSC Theses and Dissertations

Introduction: It has been established that gingival inflammation is exacerbated during puberty, in women taking oral contraceptives, and during pregnancy. Increased levels of sex hormones are implicated in the changes in periodontal conditions. It has also been established that treatn1ent with fixed orthodontic appliances presents a favorable situation for plaque accumulation, making oral hygiene more difficult to maintain. Therefore, it was hypothesized that adolescents receiving orthodontic therapy during their pubertal growth peak, might be more susceptible to gingival enlargement than those being treated outside of puberty. Orthodontists often seek to treat adolescent patients during their pubertal growth peak and utilize …