Digital Commons Network^™

Causes And Consequences Of Genetic Robustness And Fragility In Hiv-1 Proteins, Suzannah J. Rihn

Student Theses and Dissertations

Genetic robustness describes a capacity to maintain function in the face of mutation. RNA viruses, like human immunodeficiency virus-1 (HIV-1), experience extremely high mutations rates in vivo, which contribute to the evolvability that permits HIV-1 to evade immune defenses. However, the compact nature of the HIV-1 viral genome, in which small or overlapping proteins are often multifunctional and essential, often necessitates a strong pressure to conserve functional roles, which is at opposition with immunological pressures to diversify. Under such conditions, and in consideration of the relatively rapid replication cycle of HIV-1, natural selection for robustness would be predicted to be …

Functional And Structural Studies Of The Human Voltage-Gated Proton Channel, James Anthony Letts

Student Theses and Dissertations

The activity of voltage-gated cation channels underlies the action potentials that allow for neuronal signaling and muscle contraction. The canonical family of voltage-gated K⁺, Na⁺ and Ca²⁺ channels has been the subject of extensive electrophysiological, biophysical, genetic, biochemical and structural characterization since the 1950s. These channels all share a conserved six-transmembrane helix topology (S1-S6) in which the first four transmembrane helices (S1-S4) form the regulatory voltage-sensor domain and the last two transmembrane helices (S5 and S6) comprise the ion-conducting pore domain. It was thought that all voltage-gated cation channels shared this conserved domain architecture. However, this …

Studies Of A Novel Phage Lytic Enzyme, Plyss2, Daniel B. Gilmer

Student Theses and Dissertations

Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. Methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes (group A streptococci – GrAS) cause potentially fatal human diseases. These are just three of the many Gram-positive pathogens for which resistance to leading antibiotics has emerged. The goal of this work was to develop a novel antimicrobial treatment to combat these and other antibiotic-resistant pathogens. We identified a novel bacteriophage lysin, derived from an S. suis phage termed PlySs2 (phage lysin from S. suis 2). This thesis is divided into four main …

Abdominal-B Neurons Control Drosophila Virgin Female Receptivity, Jennifer J. Bussell

Student Theses and Dissertations

To choose their mates, male and female vinegar flies (Drosophila melanogaster) perform a duet of stereotyped, sexually dimorphic courtship behaviors, a suite of sensory back-and-forth that offers an excellent model for studying the neural circuitry of complex behavior (Dickson, 2008). However, the study of Drosophila courtship has focused overwhelmingly on the male, and little is known about how the female evaluates male courtship to decide whether to mate and how she executes that decision by slowing down and opening vaginal plates, a process known as receptivity. To expand the mechanistic understanding of Drosophila receptivity, we set out to identify neurons …

High Resolution Maps Of The Vasculature Of An Entire Organ, Oppenheim N. Jacob

Student Theses and Dissertations

The structure of vascular networks represents a great, unsolved problem in anatomy. Network geometry and topology differ dramatically from left to right and person to person as evidenced by the superficial venation of the hands and the vasculature of the retinae. Mathematically, we may state that there is no conserved topology in vascular networks. Efficiency demands that these networks be regular on a statistical level and perhaps optimal. We have taken the first steps towards elucidating the principles underlying vascular organization, creating the first map of the hierarchical vasculature (above the capillaries) of an entire organ. Using serial blockface microscopy …

Coordinating Stem Cell Behavior In The Hair Follicle, Chiung-Ying Chang

Student Theses and Dissertations

Tissue stem cells perform important functions throughout an organism's life. They generate new cells to replenish cells that are lost during normal wear and tear or in response to acute injury. Remarkably, hair follicles naturally undergo repetitive cycles of regeneration and degeneration, a process that is accomplished with the support of stem cells within the hair follicles. It is this feature that makes this miniorgan an attractive model system to study stem cell biology. Interestingly, hair follicle is home to two distinct stem cell populations: epithelial hair follicle stem cells (HFSCs), which contribute to the formation of hair shafts, and …

The Neuropeptide Regulation Of Host-Seeking Behavior In Aedes Aegypti Mosquitoes, Jeff Liesch

Student Theses and Dissertations

Aedes aegypti mosquitoes are the principal vectors for several human diseases including Dengue Fever, which causes ~400 million cases and ~24,000 deaths per year (Bhatt et al., 2013; WHO, 2002). Novel strategies to combat mosquito-borne diseases are needed for A. aegypti and other mosquitoes such as the malaria vector Anopheles gambiae. Our goal was to discover new ways to interfere with the ability of a mosquito to locate a human host for a blood meal. Currently, the mechanistic basis of host-seeking and its regulation remain incompletely understood. Although it is known that mosquitoes require human odor cues to locate a …

Taming A Potent Mutator: Identification And Characterization Of Novel Mechanisms Of Regulating Antibody Diversification In B-Lymphocytes, Rebecca Kyle Delker

Student Theses and Dissertations

Often the needs of an organism exceed the number of genes in the genome. Thus, modification of the genes, themselves, or of the gene products is necessary. This becomes particularly important in cells of the immune system, which have to combat a virtually infinite array of foreign pathogens. Blymphocytes, the mediators of humoral immunity, have developed extensive mechanisms of gene diversification collectively known as antibody diversification. Antibody diversification, a set of processes necessary for an organism to mount a specific and robust immune response, relies on Activation Induced Cytidine Deaminase (AID) to initiate two of such processes: Somatic Hypermutation (SHM) …

The Origin Of Multiple Sclerosis Revisited: The Case For A Soluble Toxin, Kareem Rashid Rumah

Student Theses and Dissertations

After nearly two hundred years of scientific inquiry, the cause of Multiple Sclerosis (MS) remains unknown. Although generally considered an autoimmune disease, recent pathological findings have challenged the longstanding autoimmune view of MS. Indeed, lesions that are just hours past their initial onset display evidence of cellular degeneration in the absence of an inflammatory infiltrate. This seminal finding begs the fundamental question, if immune cells do not participate in early tissue damage in MS, what is the mysterious triggering agent? In the first half of this thesis, I will propose that a soluble bacterial toxin, Clostridium perfringens epsilon toxin (ETX), …

Identification Of A Functional Hotspot On Ubiquitin Required For Stimulation Of Methyltransferase Activity On Chromatin, Matthew Thomas Holt

Student Theses and Dissertations

Histone post-translational modifications modulate chromatin structure and function either by directly altering the intrinsic physical properties of the chromatin fiber or by nucleating the recruitment and activity of a host of transacting nuclear factors. Histone ubiquitylation is one class of histone PTMs where the 76 amino acid protein, ubiquitin, is ligated to the ε-nitrogen of a lysine amino acid residue within the histone substrate. 36 unique ubiquitin sites across the 4 canonical histones have been annotated, with 7 of these sites associated with chromatin-templated processes. One such modification, the ubiquitylation of Histone H2B at lysine 120 (H2B-Ub) is enriched at …

Chromatin Control Of The Antiviral Response To Influenza, Jessica Sook Yuin Ho

Student Theses and Dissertations

A key development for our understanding of the mechanisms that control gene expression has been the finding that the histones recruit proteins with effector functions to chromatin. This is mediated primarily by post-translational modifications that occur on the histone N-terminal domains ("tails"). Single or combinations of histone tail modifications serve as scaffolds for protein complexes controlling transcription or co-transcriptional processes, thus impacting gene expression. Histone tail modifications are regulated by multiple, often overlapping pathways in the cell, and as such, present an important regulatory "node" through which the cell is able to integrate and respond to environmental signals. However, a …

Mechanism And Evolutionary Origins Of Hiv-1 Virion Entrapment By Tetherin, Siddarth Venkatesh

Student Theses and Dissertations

The cellular restriction factor, tetherin, prevents HIV-1 and other enveloped virus particles from being disseminated into the extracellular milieu by infiltrating their envelopes and by physically crosslinking them to the cell surface. However, the mechanisms underlying virion retention have not yet been fully delineated. In this body of work, we employed biochemical assays and engineered tetherin proteins to demonstrate conclusively that virion tethers are composed of the tetherin protein itself, and to elucidate the configuration and topology that tetherin adopts during virion entrapment. We demonstrated that tetherin dimers adopt an "axial" configuration, in which pairs of transmembrane domains or pairs …

Mutations In A Mechanosensitive Channel Enable Intravascular Metaststic Cell Survival, Paul William Furlow

Student Theses and Dissertations

Next-generation sequencing technology has revolutionized cancer biology by accelerating the unbiased discovery of mutations across human cancers 1-4. Despite this advance, it remains unknown whether there exist mutations that function specifically to drive steps in the metastatic cascade independent from, or perhaps even to the detriment of, tumor initiation and growth 5. The development and implementation of a discovery framework that integrates next-generation RNA-sequencing with in vivo selection, has identified recurrent non-synonymous amino acid mutations that are enriched in metastatic breast cancer cells and predicted to significantly alter protein function. The pro-metastatic role of one of these mutations—a nonsense alteration …

Stochastic Activation Of Enhancers In The Innate Immune Response By The Histone Demethylase Jmjd2d, Rohit Chandwani

Student Theses and Dissertations

The architecture of chromatin is complex and plays a substantial role in all of the biological processes involving DNA. In particular, transcriptional activation depends on the interplay of dozens of chromatin modifiers to establish an epigenetic landscape permissive of gene transcription. Among the most dynamic histone modifications are the acetylation and methylation at histone 3 lysine 9, but the precise roles of their modifiers in conserved transcriptional programs remain unknown. Using the poly I:C-induced transcriptional response in MEFs as our model, we find that JMJD2d is a positive regulator of type I interferon responses. siRNA-depletion of the H3K9 demethylase JMJD2d …

The Structural And Biochemical Characterization Of Salmonella Host Specificity Determinant Gifsy-2 Gene E, Amanda C. Kohler

Student Theses and Dissertations

Salmonella enterica continues to be a significant public health concern, causing an estimated 93.8 million cases of non-typhoidal salmonellosis and 21 million cases of typhoid fever worldwide each year. There are thousands of Salmonella enterica serovars, some with a very specific host set, and others that cause disease in rodents, birds, livestock, domestic fowl, and humans alike. In recent years, there has been much progress in the delineation of Salmonella infection, with the goal of understanding Salmonella pathogenesis at the molecular level. Salmonella produces many different effector proteins capable of interacting with and altering numerous biological pathways in the host …

Split Inteins: From Mechanistic Studies To Novel Protein Engineering Technologies, Neel H. Shah

Student Theses and Dissertations

Inteins are auto-processing protein domains that carry out a post-translational process known as protein splicing. This process is characterized by excision of the intein (intervening protein) domain from within a larger polypeptide sequence with concomitant ligation of the flanking extein ( external protein) regions through a native peptide bond. Remarkably, a small subset of all inteins are naturally transcribed and translated as two fragments that efficiently associate and carry out the same biochemical process in trans, and these split inteins are potentially powerful tools for protein engineering. Recently, a split intein from the cyanobacterium Nostoc punctiforme (Npu) was discovered that …

Transcriptome-Wide Characterization Of Apobec1-Catalyzed Rna Editing Events In Macrophages, Claire Ellen Hamilton

Student Theses and Dissertations

RNA editing refers to the process by which the sequence of RNA is altered through the insertion, deletion or modification of specific nucleotides. Editing of mRNA transcripts can increase the informational complexity encoded by the genome by producing alternative protein isoforms through specific posttranscriptional RNA editing events. Additionally, RNA editing in non-coding regions of mRNA transcripts has been shown to influence gene expression in a tissue-specific manner. In mammals, mRNA editing serves a diverse set of biological roles in neuronal function, host defense and lipid metabolism. The major mRNA editors acting in mammals include the adenosine deaminases acting on RNA …

Rna Deregulation In Metastatic Breast Cancer, Christina Beate Marney

Student Theses and Dissertations

Breast cancer is the most commonly diagnosed and second highest cause of cancer-related mortality in women, with the majority of deaths associated with metastatic spread of tumors to distal organs. The metastatic process involves multiple sequential steps including invasion of the surrounding stroma, intravasation into lymph or blood vessels, survival during transport with successful evasion of the immune system, extravasation and final outgrowth in the new microenvironment. At each step cells acquire new properties through the alteration of gene expression profiles. While a great deal of effort has been made towards understanding the underlying genetic mutations associated with enhanced motility …

Identification Of A Microrna Network That Regulates Melanoma Metastasis And Angiogenesis By Targeting Apoe, Nora Pencheva

Student Theses and Dissertations

Metastatic melanoma, a prevalent and deadly form of skin cancer, remains an aggressive clinical outcome that lacks effective preventative and/or curative therapeutics. Patients diagnosed with advanced metastatic melanoma face a dreaded 10-year survival rate of less than 10%. By performing in vivo selection for highly metastatic melanoma cells, we systematically identified three microRNAs (miRNAs) that promoted metastasis across multiple mutationally diverse human melanoma subtypes. These miRNAs were found to promote metastasis by enhancing the invasive capacity of melanoma cells and also by allowing melanoma cells to recruit endothelial cells into the metastatic niche, leading to enhanced metastatic angiogenesis. Importantly, the …

Physical Environment And Women's Physical Activity Behaviors, Beth Ann Brisky

All Graduate Theses, Dissertations, and Other Capstone Projects

This study was developed using the Ecological Model (Stokols, 1992). The purpose of this study was to determine women's perceptions of the physical environment and the relationship between perceptions and physical activity behaviors. The study also analyzed women's non-motorized transportation behaviors, including walking and cycling to get from place to place. An email was sent to 526 female Minnesota State University, Mankato employees to ask them to participate in an electronic survey. The survey was developed using two of Sallis's (2013a, 2013b) instruments, Neighborhood Quality of Life Study survey and Neighborhood Environment Walkability Scale-Confirmatory Factor Analysis survey. The survey consisted …

Benchmarks 2014, January 31, The Rockefeller University

BenchMarks 2014

BenchMarks. Friday, January 31, 2014

The community newsletter of The Rockefeller University

BenchMarks is published monthly and is distributed on the campus of The Rockefeller University. It produced by the Office of Communications and Public Affairs

Utah Shrubland Management, Thomas A. Monaco, Kari E. Veblen, Justin Williams

Wildland Resources Faculty Publications

This Winter 2014-2015 Newsletter discusses accomplishments over the past year for the Shrubland Management project. We highlight the Ecological Sites and targeted shrubs at the ranch owned by Mr. Rial Berry in Cedar Fort, Utah.

Influence Of Group Size On The Success Of Wolves Hunting Bison, Daniel R. Macnulty, Aimee G. Tallian, Daniel R. Stahler, Douglas W. Smith

Wildland Resources Faculty Publications

An intriguing aspect of social foraging behavior is that large groups are often no better at capturing prey than are small groups, a pattern that has been attributed to diminished cooperation (i.e., free riding) in large groups. Although this suggests the formation of large groups is unrelated to prey capture, little is known about cooperation in large groups that hunt hard-to-catch prey. Here, we used direct observations of Yellowstone wolves (Canis lupus) hunting their most formidable prey, bison (Bison bison), to test the hypothesis that large groups are more cooperative when hunting difficult prey. We quantified the relationship between capture …

Effects Of Climatic Variation And Reproductive Trade-Offs Vary By Measure Of Reproductive Effort In Greater Sage-Grouse, Danny Caudill, Michael R. Guttery, Brent Bibles, Terry A. Messmer, Gretchen Caudill, Erin Leone, David K. Dahlgren, Renee Chi

Wildland Resources Faculty Publications

Research on long-lived iteroparous species has shown that reproductive success may increase with age, until the onset of senescence, and that prior reproductive success may influence current reproductive success. Such complex reproductive dynamics can complicate conservation strategies, especially for harvested species. Further complicating the matter is the fact that most studies of reproductive costs are only able to evaluate a single measure of reproductive effort. We systematically evaluated the effects of climatic variation and reproductive trade-offs on multiple reproductive vital rates for greater sage-grouse (Centrocercus urophasianus; sage-grouse), a relatively long-lived galliforme of conservation concern throughout western North America. Based on …

Eating Attitudes And Reasons For Exercise Among Physically Active College Female Students, Ann Weber

Graduate Research Theses & Dissertations

Disordered eating attitudes and exercise behaviors are important factors when studying the continuum of eating disorders. An individual's attitude toward eating may influence other behaviors and thoughts toward health and exercise. A convenience sample study was used to examine the relationship between eating attitudes, reasons for exercise, and age among 190 physically active female college students ages 18 to 57. Participants completed the Disordered Eating Attitude Scale (DEAS) and Reasons for Exercise Inventory (REI). Level of exercise was self-reported by the participants and categorized as low, moderate, or high according to the Physical Activity Guidelines for Americans. Pearson's Correlation determined …

Food Elimination Based On Alcat Testing And The Effect On Overall Body Inflammation, Dawn Michelle Herbig

Graduate Research Theses & Dissertations

Background: Growing evidence suggests that obesity is associated with systemic inflammation. The level of inflammation can be exacerbated by one or more existing food intolerances. Furthermore, studies have shown that diet quality, not quantity, plays an important role in potential inflammation caused by foods. It is therefore, important to determine if dietary patterns alone or in combination with increased adiposity have a greater effect on systemic inflammation and body composition.||Objective: Hence, the purpose of this study was to examine the effect of food elimination using the ALCAT food elimination protocol, on body composition and overall body inflammatory markers.||Methods: One hundred …

Medicine@Yale March/April 2014 Volume 10, Issue 1, 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 December 2014 Volume 10, Issue 3, 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.

Effects Of Urbanization On Sediment Microbial Communities In Lotic Ecosystems, Bradley Drury

Master's Theses

The world is becoming increasingly urbanized, with the majority of the world's population now living in urban areas. Urbanization has the potential to significantly alter lotic ecosystems and the services they provide. Benthic microbial communities are key components of lotic ecosystems due to their contributions to primary production and nutrient cycling. Two types of human inputs associated with urbanization that may impact benthic microbial communities in lotic ecosystems are the input of wastewater treatment effluent and the input of emerging contaminants, including pharmaceuticals and personal care products. This work examines the effects of treated WWTP effluent on benthic microbial communities …

Masthead, Journal Of Law And Health

Journal of Law and Health

No abstract provided.