Life Sciences Commons^™

Analysis Of Protein-Coding Genetic Variation In 60,706 Humans, Monkol Lek, Konrad J. Karczewski, Eric V. Minikel, Kaitlin E. Samocha, Eric Banks, Timothy Fennell, Anne H. O'Donnell-Luria, James S. Ware, Andrew J. Hill, John Blangero

Human Genetics Publications

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong …

Feel Or Perspective?, Mark Rowlands

Animal Sentience

The title of Klein & Barron’s well-argued and thought-provoking target article is, “Insects have the capacity for subjective experience.” However, they also frame their claim using the term “consciousness,” which they seem to take as equivalent to “subjective experience.” This assumed equivalence, I shall argue, is problematic in a way that might vitiate their central argument.

Modeling And Analysis Of Germ Layer Formations Using Finite Dynamical Systems, Alexander Garza, Megan Eberle, Eric A. Eager

Spora: A Journal of Biomathematics

The development of an embryo from a fertilised egg to a multicellular organism proceeds through numerous steps, with the formation of the three germ layers (endoderm, mesoderm, ectoderm) being one of the first. In this paper we study the mesendoderm (the tissue that collectively gives rise to both mesoderm and endoderm) gene regulatory network for two species, \textit{Xenopus laevis} and the axolotl (\textit{Ambystoma mexicanum}) using Boolean networks. We find that previously-established bistability found in these networks can be reproduced using this Boolean framework, provided that some assumptions used in previously-published differential equations models are relaxed. We conclude by discussing our …

Transforming The Wku Office Of Sustainability's Front Yard Into An Edible Landscape, Alexandra Hezik

Mahurin Honors College Capstone Experience/Thesis Projects

Since moving to 503 Regents Avenue in Fall 2013, the WKU Office of Sustainability has served as a sustainable best practices demonstration home for the WKU and Bowling Green communities. Not only does the house in which the Office of Sustainability is located serve as an educational tool for people, but also the landscape. In May 2014, the WKU Community Garden was established in the backyard. The transformation of the Office of Sustainability’s front lawn into an edible landscape began on April 1, 2015. The purpose of this project is to demonstrate an alternative to conventional lawns.

U.S. Drought Monitor, August 16, 2016, David Miskus

United States Agricultural Commodities in Drought Archive

Drought map of U.S. for August 16, 2016 (8/16/16) plus: U.S. crop areas experiencing drought (map), Approximate percentage of crop located in drought, by state (bar graph), Percent of crop area located in drought, past 52 weeks (line graph) for: Corn, Soybeans, Hay, Cattle, Winter wheat.

The Effects Of Ivermectin On Brugia Malayi Females In Vitro: A Transcriptomic Approach, Cristina Ballesteros, Lucienne Tritten, Maeghan O'Neill, Erica Burkman, Weam I. Zaky, Jianguo Xia, Andrew Moorhead, Steven A. Williams, Timothy G. Geary

Biological Sciences: Faculty Publications

Lymphatic filariasis and onchocerciasis are tropical diseases caused by infections with parasitic nematodes. Resulting chronic diseases can be strongly blinding and disfiguring, and contribute to an entrenched cycle of poverty in affected populations. Ivermectin is one of the pivotal drugs used to control these infections. The mechanism of antifilarial action of the drug is incompletely resolved. It kills circulating larval stages (microfilariae), but only reversibly sterilizes adult worms without killing them. Our limited understanding of the involved mechanisms hampers treatment optimization and sustainability of the efficacy of the drug, and investigations into its pharmacology are of paramount importance. Working with …

Building From The Hiv Response Toward Universal Health Coverage, Jonathon Jay, Kent Buse, Marielle Hart, Robert Marten, Scott Kellerman, Morolake Odetoyinbo, Jonathan D. Quick, Timothy Evans, Peter Piot, Mark Dybul, Agnes Binagwaho

Dartmouth Scholarship

Universal health coverage (UHC) has gained prominence as a global health priority. The UHC movement aims to increase access to quality, needed health services while reducing financial hardship from health spending, particularly in low- and middle- income countries.
As a policy agenda, UHC has been identified primarily with prepayment and risk-pool- ing programs. While financing policies provide important benefits, increasing access to health services will require broader reforms.
For lessons, the UHC movement should look to the global HIV response, which has confronted many of the same barriers to access in weak health systems. Considerable success on HIV has resulted …

Assessing The Long-Term Welfare Effects Of The Biological Control Of Cereal Stemborer Pests In East And Southern Africa: Evidence From Kenya, Mozambique And Zambia, Soul Kifouly G. Midingoyi, Hippolyte D. Affognon, Ibrahim Macharia, Georges Ong'amo, Esther Abonyo, Gerphas Ogola, Hugo De Groote, Bruno Leru

All Peer-Reviewed Publications

The International Centre of Insect Physiology and Ecology (icipe), undertook a biological control (BC) programme for control of stemborers from 1993 to 2008, to reduce cereal yield losses due to stemborer attack in East and Southern Africa. The programme released four biological control agents-the larval parasitoids Cotesia flavipes and Cotesia sesamiae, the egg parasitoid Telenomus isis and the pupal parasitoid Xanthopimpla stemmator-to control the economically important stemborer pests Busseola fusca, Chilo partellus and Sesamia calamistis. Two of the natural enemies that were released got established and spread to many localities in the region. This study adopted the economic surplus model …

Datagauge: A Model-Driven Framework For Systematically Assessing The Quality Of Clinical Data For Secondary Use, Jose Franck Diazvasquez

Dissertations and Theses (Open Access)

There is growing interest in the reuse of clinical data for research and clinical healthcare quality improvement. However, direct analysis of clinical data sets can yield misleading results. Data Cleaning is often employed as a means to detect and fix data issues during analysis but this approach lacks of systematicity. Data Quality (DQ) assessments are a more thorough way of spotting threats to the validity of analytical results stemming from data repurposing. This is because DQ assessments aim to evaluate ‘fitness for purpose’. However, there is currently no systematic method to assess DQ for the secondary analysis of clinical data. …

The Farm Newsletter, Usu Student Organic Farm

USU Student Organic Farm Newsletter

Due to the start of fall semester, the majority of our farm workers will not be available during regular pickup hours. Starting the week of August 29 - September 3, pick-up time for all CSA members will permanently change to Saturday from 10:00am to 12:00pm. All pick-ups will take place at the farm, which is located at 1750 N 800 E in Logan.

Contribution Of A Putative Up Element Dna Sequence To The Activity Of A Newly Identified Phage Promoter, Courtney Hamilton

Mahurin Honors College Capstone Experience/Thesis Projects

In transcription, a universal step in gene expression, information from a DNA sequence is copied into RNA. A key component in gene expression is the promoter sequence, a region of DNA to which RNA polymerase binds during the initiation of transcription of downstream genes. Most bacterial promoters contain a -10 and a -35 sequence that are bound by the RNA polymerase. Some promoters also contain an Upstream Promoter (UP) element. UP elements have been shown to boost promoter activity. We recently identified a new promoter in a mutant bacteriophage that grows on a bacterial host that prevents antitermination of phage …

Functional Characteristics And Quality Of Ultraviolet-Irradiated Partially Insoluble Fish Gelatin As Shark Fin Analogs, Yu Wei Chang, Chang Shu Liu, Chia Chi Chiang, Jenn Shou Tsa, Wen Chieh Sung

Journal of Marine Science and Technology–Taiwan

Tilapia skin gelatin powder was used to parpare shark fin analogs. Experimental samples were exposed to ultraviolet (UV) irradiation at 612, 1224, 1836, 2448, 3060, and 3672 mJ/cm2 . Fish gelatin exposed to UV at 1836 mJ/cm2 became partially insoluble. UV exposure reduced the transmittance of amide I at 1630 cm-1, amide II at 1480-1575 cm-1, and amide III at 1237 cm-1 in Fourier transform infrared spectra. UV treatment at 612 mJ/cm2 significantly reduced the gel strength of fish gelatin, whereas higher UV exposure increased the gel strength. UV irradiation at up to 3060 mJ/cm2 increased the b* value (yellowness) …

Regulation Of Durable Adaptive Immune Response By The C-Myc-Ap4 Transcriptional Cascade, Chun Chou

Arts & Sciences Graduate Student Theses and Dissertations

The process of amplifying immune responses by expanding a small number of antigen-specific cells, termed clonal expansion, is an important feature of the adaptive immunity. Whereas clonal expansion of cytotoxic T lymphocytes is required for complete eradication of intracellular pathogens, proliferation of B lymphocytes in the germinal centers (GC) is critical for generating a diverse immunoglobulin gene repertoire from which protective antibody carrying multiple mutations can arise. While the proto-oncogene c-MYC is absolutely required for the activation and cell cycle initiation in lymphocytes, its expression is temporally restricted. Activated lymphocytes, however, continue to proliferate after c-MYC levels decay to maximize …

Functions For Murine Norovirus Protein Ns1/2 In Mice And Cells, Broc Taylor Mccune

Arts & Sciences Graduate Student Theses and Dissertations

Noroviruses are a leading cause of epidemic gastroenteritis and a major health burden worldwide. One source for outbreaks is individuals who shed virus asymptomatically and persistently. Viral persistence is a successful strategy for viruses to spread, but the mechanisms and consequences of norovirus persistent infection are unknown. In this dissertation, we sought to determine the norovirus determinant(s) of persistence and explore the functions of the associated viral molecules.To determine the viral determinants of persistent infection and tropism, we used the murine norovirus model system in mice. Using plasmid infectious clones for persistent strain CR6 and non-persistent strain CW3, we mapped …

Molecular Mechanisms Mediating The Effects Of Acute Dietary Vitamin A Deficiency On A Defined Model Human Gut Microbiota, Matthew Charles Hibberd

Arts & Sciences Graduate Student Theses and Dissertations

Micronutrient deficiencies represent a form of "hidden hunger" that afflict two billion people worldwide. To test the hypothesis that dietary micronutrient deficiency has differential effects on members of the human gut microbiota, a consortium containing 92 sequenced phylogenetically diverse bacterial strains was introduced into germ-free mice. Recipient animals were subjected to a diet oscillation that began with highly defined micronutrient-sufficient diet followed by a derivative diet with one of four types of single micronutrient deficiency, or a diet representing combined deficiencies, followed by return to the original sufficient diet. Times-series studies of microbial community structure and transcriptome revealed that acute …

Tau Prion Strains In Cells, Mice, And Patients, David Winland Sanders

Arts & Sciences Graduate Student Theses and Dissertations

Prion-like propagation of tau aggregation may underlie the stereotyped progression of pathology along neuronal networks in neurodegenerative tauopathies such as Alzheimer’s disease. It has become increasingly clear that unique conformations (“strains”) of prion protein (PrP) link aggregate structure to clinical phenotypes in human prion diseases. Intriguingly, vast phenotypic diversity in pathological and clinical presentation is also observed in tauopathies. The mechanisms that account for this phenotypic diversity are completely unknown. During my dissertation work, I put forward and tested the hypothesis that distinct tau amyloid conformations (or “strains”) are responsible for unique tauopathies. First, I found that in experimental models, …

Neural Representation Of Vocalizations In Noise In The Primary Auditory Cortex Of Marmoset Monkeys, Ruiye Ni

McKelvey School of Engineering Graduate Student Theses & Dissertations

Robust auditory perception plays a pivotal function in processing behaviorally relevant sounds, particularly when there are auditory distractions from the environment. The neuronal coding enabling this ability, however, is still not well understood. In this study we recorded single-unit activity from the primary auditory cortex of alert common marmoset monkeys (Callithrix jacchus) while delivering conspecific vocalizations degraded by two different background noises: broadband white noise (WGN) and vocalization babble (Babble).

Noise effects on single-unit neural representation of target vocalizations were quantified by measuring the response similarity elicited by natural vocalizations as a function of signal-to-noise ratio (SNR). Four consistent response …

Utilization Of Cholera Toxin B As An Adjuvant For The Subunit Pspa Vaccine, Provides Effective Protection Against Streptococcus Pneumoniae Challenge, Daniel R. Pinho

Seton Hall University Dissertations and Theses (ETDs)

Streptococcus pneumoniae is a prevalent human pathogen associated with pneumonia. It is estimated that approximately 1 million people around the world die each year, specifically with young children and the elderly comprising a significant portion. Currently, antibiotics can treat the infection but individuals such as the young or elderly are more susceptible to bodily damage from symptoms, such as pneumonia, meningitis, and sepsis, thus require more preventive measures. As a result, vaccinations are a key solution to providing effective protection against infectious pathogens. Presently, two vaccinations exist in the market: PPSV₂₃ and PCV₁₃, which only protect against …

Motor Adaptation And Automaticity In People With Parkinson’S Disease And Freezing Of Gait, Samuel Thomas Nemanich

Arts & Sciences Graduate Student Theses and Dissertations

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by cell death in the substantia nigra pars compacta, resulting in motor symptoms of tremor, rigidity, bradykinesia and gait impairment. Freezing of gait (FOG) is one serious gait disturbance, characterized by a transient inability produce effective stepping during walking and turning, and affects roughly half of people with PD at some point during their disease. Despite the ongoing research on the behavioral, neurological, and cognitive characteristics of people with FOG (PD+FOG), the mechanisms underlying freezing are still poorly understood. The overall aim of this work was to further investigate motor behavior …

New Tools For Viscoelastic Spectral Analysis, With Application To The Mechanics Of Cells And Collagen Across Hierarchies, Behzad Babaei

McKelvey School of Engineering Graduate Student Theses & Dissertations

Viscoelastic relaxation spectra are essential for predicting and interpreting the mechanical responses of materials and structures. For biological tissues, these spectra must usually be estimated from viscoelastic relaxation tests. Interpreting viscoelastic relaxation tests is challenging because the inverse problem is expensive computationally. We present here (1) an efficient algorithm and (2) a quasi-linear model that enable rapid identification of the viscoelastic relaxation spectra of both linear and nonlinear materials. We then apply these methods to develop fundamental insight into the mechanics of collagenous and fibrotic tissues.

The first algorithm, which we term the discrete spectral approach, is fast enough to …

Behavioral And Neurophysiological Mechanisms Of Recovery Post-Stroke, Lenny Eveline Ramsey

Arts & Sciences Graduate Student Theses and Dissertations

Strokes can affect very different behavioral domains causing deficits in language, memory, visual attention and movement. This range of deficits is caused by stroke lesions that occur in different locations, and it reflects both the local structural damage as well as remote and widespread neurophysiological abnormalities of structurally normal regions of the brain. The recovery of behavioral deficits depends both on psychosocial factors like age and education, whose brain substrates are presently poorly defined, structural variables such as lesion size and location, and neurobiological repair mechanisms both locally near the lesion and network-wide.In the current work we hypothesized that behavioral …

Ecological And Genetic Consequences Of Climate Change Impacting Species Distributions, With Specific Cases In Whitebark Pine (Pinus Albicaulis Engelm.), Jennifer A. Gruhn

Arts & Sciences Graduate Student Theses and Dissertations

Climate is widely recognized as a primary factor contributing to species distribution limits. In turn, species’ geographic ranges have contracted and expanded in concert with Earth’s climatic history and are predicted to shift in response to future climate change. We investigated the ecological and genetic consequences of species distributions in flux with their historical, current, and projected future climatic environments. Chapter 1 introduces themes and background information related to the thesis research found in Chapters 2 through 4. In Chapter 2, we questioned the extent to which ancestral climate-related traits are conserved through vast periods of evolutionary time spanning the …

The P38mapk-Mk2-Hsp27 Axis Regulates The Mrna Stability Of The Pro-Tumorigenic Senescence-Associated Secretory Phenotype, Hayley Reynolds Moore

Arts & Sciences Graduate Student Theses and Dissertations

Protecting the genome is a vital aspect of safeguarding organismal health. Inability to efficiently and effectively replicate the genome or repair damage the genome may encounter can lead to mutational accumulation or senescence, both of which are drivers of multiple diseases including cancer. Understanding the mechanisms by which the genome is maintained, as well as the consequences of repeated rounds of replication or exposure to DNA damaging agents, will allow for greater understanding of the diseases they promote as well as development of targeted therapies aimed at mitigating the detrimental effects of genomic insult. The first section of my work …

Population Structure And Mating Dynamics In The Social Amoeba Dictyostelium Discoideum, Tracy Edwards Douglas

Arts & Sciences Graduate Student Theses and Dissertations

Successfully investigating the evolution and maintenance of sex and mating systems can often have as much to do with choosing the right study system as it has to do with asking the right questions. Dictyostelium discoideum has long been the focus of researchers interested in understanding a number of biological processes, such as motility, chemotaxis and development. More recently, attentions have shifted to include questions about the evolution of social and sexual interactions both within and between species. The D. discoideum life cycles, both asexual and sexual, are uniquely social, each requiring a costly sacrificial act. This offers an ideal …

Action Of Snail1 Protein Is Critical For Fibrosis, Hirak Biswas

Arts & Sciences Graduate Student Theses and Dissertations

Hypoxic injury to the heart causes cardiac fibrosis leading to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor which has been implicated in fibrosis following organ injury. To investigate the role of SNAIL1 in cardiac fibrosis, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 is expressed in the infarcted myocardium, especially in the myofibroblasts. Utilizing cardiac fibroblasts in-vitro we demonstrate that pro-fibrotic factors and collagen increases SNAIL1 in cardiac fibroblasts. By knocking out SNAIL1 in cardiac fibroblasts in-vitro, we demonstrate that SNAIL1 is required for adoption …

Differential Associations Of Stress And Cortisol With Brain Structure And Cognition In Cognitively Normal Older Adults, Ana Kim

Arts & Sciences Graduate Student Theses and Dissertations

The current literature shows discrepant findings as to the degree to which cumulative stress and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis are associated with brain structure and cognitive function in older adults, particularly in brain regions with high expression of receptors for glucocorticoid, and cognitive function reliant upon these regions. Past studies have been heavily focused on total hippocampus while limited studies have examined hippocampal subdivisions or other brain structures. In addition, one key moderator that may influence the associations of cumulative stress and cortisol on brain structure and cognition is the single-nucleotide polymorphisms (SNPs) of the stress-system genes, which …

Investigating Auxin Biosynthesis And Its Contribution To Virulence By Pseudomonas Syringae Pv Tomato Dc3000, Sheri Mcclerklin

Arts & Sciences Graduate Student Theses and Dissertations

Auxin is a major hormone that regulates many processes in plant development and has been shown to be important in several plant-pathogen interactions. Many microbes, including multiple pathovars of Pseudomonas syringae produce indole-3-aceitc acid (IAA), a naturally occurring auxin. However IAA production and its biosynthesis pathway remains undetermined for many bacteria including P. syringae strain DC3000, the subject of this thesis. To investigate IAA biosynthesis by DC3000, I examined IAA production in cultures fed with different pathway intermediates. I show that DC3000 produces IAA in culture and cultures supplemented with Indole-3-acetaldehyde (IAAld) produced high levels of IAA, indicating that IAAld …

Regulation Of Transcription And Stress Response By Card In Mycobacteria, Ashley Louise Garner

Arts & Sciences Graduate Student Theses and Dissertations

Mycobacterium tuberculosis, the causative agent of Tuberculosis, infects over one third of the world's population. To control this epidemic, we must develop new chemotherapeutic strategies for treatment, which requires further insight into the physiology of this bacterium. Previous studies have identified CarD as a transcriptional regulator essential during both acute and persistent infection. Depletion of CarD sensitizes strains to a diverse panel of stresses and deregulates several hundred genes and ribosomal RNA (rRNA) which suggested that CarD may be a transcriptional regulator. Chromatin immunoprecipitation sequencing experiments showed that CarD was localized to promoters throughout the genome, suggesting that CarD regulates …

The Role Of Epidermal Enhancer 923 In The Chromatin Architecture And Transcriptional Regulation Of The Epidermal Differentiation Complex, Inez Oh

Arts & Sciences Graduate Student Theses and Dissertations

The epidermis covers the surface of the skin and provides a functional barrier across the entire body. Epidermal cells or keratinocytes proliferate in the innermost basal layer and migrate upwards into the suprabasal spinous and granular layers as they differentiate, and finally into the terminally differentiated outermost stratum corneum. Keratinocytes undergoing terminal differentiation are marked by tissue-specific concomitant expression of genes encoded in the Epidermal Differentiation Complex (EDC) locus. The EDC genes are organized into four gene families - S100, Sprr, Lce, and Flg-like, which are coordinately expressed upon activation of the terminal differentiation program in keratinocytes. The molecular mechanisms …

Mechanisms Of Extracellular Vesicle Biogenesis, Charles Eldon Jackson

Arts & Sciences Graduate Student Theses and Dissertations

Extracellular vesicles (EVs) are important mediators of intercellular communication. Different types of EVs are released from cells by either fusion of late endsomal multivesicular bodies with the plasma membrane (exosomes) or direct budding from the plasma membrane (ectosomes). Topologically equivalent processes including intralumenal vesicle formation for degradation in the endosomal pathway and virus budding from the plasma membrane depend on the ATPase VPS4 and its Endosomal Sorting Complex Required for Transport (ESCRT)-III substrates for membrane fission and release. Whether this machinery is generally required for EV biogenesis has, however, been the subject of debate. Studies of the EV proteome from …