Life Sciences Commons^™

Transcription Initiation And Termination Of Chemically Synthesized Small Rna Expression Vectors, Jose Cobo

Dissertations, Theses, and Capstone Projects

Synthetic DNA-based small RNA expression vectors offer potential advantages over chemically synthesized RNA, such as lower cost, greater chemical stability, easier synthesis and longer shelf life. We are working to develop a novel biomedical technology that employs synthetic single-stranded circular oligonucleotides (coligos) as promoter-independent small RNA expression vectors. Coligos were initially designed to code for pre-miRNA mimics and were prepared by circularizing the first-strand cDNA sequence (i.e., the template strand) of selected genomic human pre-miRNAs. However, we are exploring coligos as general expression vectors for a variety of small RNAs used in biomedical research. To efficiently use coligos as a …

Mapping The Spatial And Temporal Dynamics Of Visual Percepts Elicited By A Non-Invasive Brain Stimulation Technique, Kelly Webster

Dissertations, Theses, and Capstone Projects

While many of us rely on vision to interact with and experience the world, for people with damage or disease to the eye or visual cortex, experience through this modality is extremely limited. Brain and retinal stimulation devices show exciting promise for restoring vision, but little is understood about where and when vision percepts can be induced through stimulation. Using a non-invasive brain stimulation technique called transcranial magnetic stimulation (TMS), we characterized the spatial and temporal dynamics of perception induced through brain stimulation. In the first set of experiments, we explore the importance of higher visual and non-visual areas vs. …

On The Distribution Of Genetic Variation In Ecological Communities, Isaac Overcast

Dissertations, Theses, and Capstone Projects

Biodiversity in ecological communities is structured hierarchically across spatial and temporal scales. Many open questions remain as to how this structure accumulates. For example, what are the relative contributions of dispersal versus in situ speciation? Or, how important are stochastic drift versus deterministic processes? Up to this point, these questions have been investigated by isolated disciplines (e.g. macroecology, comparative phylogeography, macroevolution) using tools and data that tend to focus on only one axis of community scale data (e.g. phylogenies, relative abundances, and/or trait information). Yet we know that there are feedbacks among processes that respond on short, medium, and long …

Activation Of The Sonic Hedgehog Effector Smoothened Counteracts L-Dopa Induced Dyskinesia By Restoring Cholinergic Interneuron Function, Lauren Malave

Dissertations, Theses, and Capstone Projects

Many types of neurons act as multimodal signaling centers. Yet, we have only limited insight into the regulation and functional consequences of neuronal co-transmission. For example, dopamine (DA) neurons, whose degeneration causes motor deficits characteristic of Parkinson’s Diseases (PD), communicate with all their targets by DA but only a selective subset of their targets using GABA, Glutamate, and the secreted cell signaling protein Sonic Hedgehog (Shh). It is unknown whether Levo-dopamine (L-Dopa) induced dyskinesia (LIDs), a severely debilitating side effect of DA supplementation in PD, might appear because DA neuron targets are exposed to high DA- but low Shh- signaling …

Experience-Dependent Changes In Nucleus Accumbens Activity Predict Cued Approach Learning: Contribution Of Nmda Receptors, Mercedes Vega Villar

Dissertations, Theses, and Capstone Projects

Animals learn associations between environmental cues and the natural rewards they predict (e.g., food, water, sex). As a result, reward-predictive cues come to trigger vigorous reward-seeking responses. Many neurons in the nucleus accumbens (NAc) become excited upon presentation of an already-learned reward-predictive cue. These NAc responses encode the motivational value of the cue and are necessary for the expression of the subsequent approach behavior. However, the precise temporal relationship between the emergence of cue-evoked excitations in the NAc and the acquisition of cued approach behavior remains unknown. In Experiment 1, NAc activity was recorded as rats learned to approach a …

Parp1-Targeted Radiotherapies, Stephen Jannetti

Dissertations, Theses, and Capstone Projects

Poly-ADP-ribosylation reactions were first reported by Chambon in 1963 as enzymatic activity that increases incorporation of ATP in the presence of nicotinamide mononucleotide. In the decades since that publication, Poly(ADP-ribose)polymerase 1 (PARP1) and the PARP family enzymes have been widely studied. PARP enzymes are currently known to play various roles in mammals, including anti-aging processes, interactions with Breast Cancer Suppressor Protein-1 (BRCA1), and DNA damage repair. A significant focus of PARP1 research has been elucidating its role in DNA damage repair. PARP1 is recruited to repair single strand DNA (ssDNA) breaks, which can become double stranded DNA (dsDNA) breaks if …

A Neural Mechanism For Capnotaxis In The Naked Mole-Rat, Michael Zions

Dissertations, Theses, and Capstone Projects

A Neural Mechanism for Capnotaxis in the Naked Mole-Rat

The Naked Mole-Rat (NM-R) is a small hairless rodent that has thrived underground in the Horn of Africa for the past 40 million years. It was first discovered in 1847, but has only been maintained in captivity and studied as a laboratory animal over the past 40 years. To date, more than 400 scientific papers have been published on this species. This is relatively few compared to established lab animals like rats and mice, but those papers contain a trove of information that has changed our understanding of the constraints of …

Blocking Visual Awareness With Continuous Flash Suppression Prevents Cognitive Control, Jonathan Lovoi

Dissertations, Theses, and Capstone Projects

Cognitive control refers to a set of functions that allow for the execution of goal-directed behavior while remaining flexible to changes in task demands. Findings addressing whether or not awareness is necessary to elicit cognitive control are inconsistent, possibly stemming from the short stimulus presentation times employed in most masking paradigms, which could prevent sufficient processing time in some cases or provide a gist of the masked stimulus in other cases. The present study examined the necessity of awareness in cognitive control using Continuous Flash Suppression (CFS) to suppress stimulus awareness for periods of time longer than possible with other …

Leveraging Antibodies For Positron Emission Tomography And Near-Infrared Fluorescence Imaging Of Cancer, Kimberly C. Fung

Dissertations, Theses, and Capstone Projects

The high specificity and affinity of antibodies make them attractive for developing drugs to diagnose and treat cancer. The overarching goal of this work is to explore the synthesis and use of antibody-based imaging agents in preclinical models of cancer. This work can be described as two-fold. In the first part, we investigated how the use of a glycans-specific bioconjugation strategy affects Fc gamma RI binding and why it results in improved in vivo performance of immunoconjugates. To do so, we used the clinically relevant positron emission tomography (PET) imaging agent, ⁸⁹Zr-DFO-pertuzumab, in mouse models of human breast cancer. …

Through The Back Door: Proteins Escape Cells Without Conventional Permission, Michael J. Cohen

Dissertations, Theses, and Capstone Projects

Proteins secreted to the extracellular environment play a fundamental role as signals, in metabolism, and a variety of other processes. The process of secretion through the endoplasmic reticulum and Golgi to the plasma membrane is well documented, and all cargo in this pathway contains a signal peptide. However, a variety of proteins secreted from eukaryotes lack a signal peptide and are called unconventionally secreted proteins. Here we discuss known mechanisms of unconventional protein secretion, as well as model proteins which follow characterized pathways. Additionally, we summarize the roles various unconventionally secreted proteins play outside of cells and suggest criteria for …

Molecular Mechanisms Underlying Migratory And Immune-Evasion Properties Of Circulating Tumor Cells, Jeannette A. Huaman

Dissertations, Theses, and Capstone Projects

Metastasis is the leading cause of cancer deaths worldwide. However, there exist only limited treatment options and they are often ineffective. An important aspect of metastasis that requires study, but has previously been understudied is circulating tumor cells (CTCs). CTCs are a critical step in the metastatic cascade. They can be analyzed for the identification of key mechanisms in metastasis. To this end, we isolated CTCs from a syngeneic mouse model of hepatocellular carcinoma (HCC) and a human xenograft mouse model of castration-resistant prostate cancer (CRPC). From these mouse models, primary tumor and CTC lines were established. Functional characterization of …

The Cortico-Motoneuronal System In The Plexina1 Knock-Out Mouse: Sculpting The Motor Response And Activity-Dependent Plasticity, John Kalambogias

Dissertations, Theses, and Capstone Projects

Higher primates, apes, and humans have cortico-motoneuronal (CM) connections between the motor cortical areas and spinal motoneurons. The CM system is thought to confer individuated finger movements and other aspects of skilled movement control; in part, by the selective CM cell they recruit, leading to fractionated patterns of muscle activity. Although CM connections have been examined using several approaches in monkeys, the presence and properties of the CM connection was elucidated in all the species using the technique of stimulus-triggered averaging (StTA). The electrophysiological signature for the CM response is short-latency EMG facilitation (post-stimulus facilitation; PStF) in individual muscles, followed …

Hur Ubiquitination By Brca1/Bard1 And Its Role In Controlling Gene Expression During Dna Damage Response, Gamage M. Aruggoda

Dissertations, Theses, and Capstone Projects

Despite our understanding of the biochemistry of the BRCA1/BARD1 E3 ligase, we know very little of the mechanism by which its cellular substrates, how they are chosen, how its E3 Ub ligase activity is regulated, which are the cofactors involved in this regulation, and how the substrates are modified during DDR. In this dissertation, I further evaluate BRCA1/BARD1-mediated E3 ligase activity and how CstF-50 and p97 regulate this reaction working as cofactors. My data show that BRCA1/BARD1 is an E3 ligase that ubiquitinates the RNA binding protein Human antigen R(HuR).

HuR is abundant in the nucleus and is transported to …

Advanced Computational Methodologies To Study Binding Free Energies Of Biomolecular Complexes, Rajat Kumar Pal

Dissertations, Theses, and Capstone Projects

Molecular recognition is the basis of biological mechanisms and is a key element to consider while formulating effective and safe drugs. Pharmaceutical drugs are designed so as to bind a target protein even at very low concentrations to alter the diseased conditions without interfering with normal biological processes. In a rational drug design process, this is achieved by acquiring information about the chemical structure and the physical and chemical properties of the target protein receptor to gain insights on how changing the chemical composition of the substrate drug could affect the protein-drug interaction and binding affinities. Computational models are used …

Mutational Analysis And Domain Characterization Of The Apolipoprotein L-1 Ion Channel, Charles M. Schaub

Dissertations, Theses, and Capstone Projects

The human innate immunity factor Apolipoprotein L-1 (APOL1) protects against Trypanosoma brucei brucei infection. Recent studies have shown recombinant APOL1 (rAPOL1) inserts into planar lipid bilayers at an acidic pH 5.6 and forms a cation-selective channel, which opens upon subsequent neutralization, pH 7.2. This corresponds with the pH changes APOL1 would encounter during endosome recycling, suggesting that APOL1 forms a pH-gated ion channel in the plasma membrane of the parasite, leading to uncontrolled ion flux and osmotic imbalance. However, structural and domain characteristics of the APOL1 channel are poorly understood, despite potential similarities to diphtheria and colicin toxins. Utilizing E. …

To Flex Or Rest: Does Adding No-Load Isometric Actions To The Inter-Set Rest Period In Resistance Training Enhance Muscular Adaptations? A Randomized-Controlled Trial, Brad J. Schoenfeld, Jozo Grgic, Bret Contreras, Kenneth Delcastillo, Andrew Alto, Cody Haun, Eduardo O. De Souza, Andrew D. Vigotsky

Publications and Research

We aimed to investigate the effects of resistance training (RT) combined with no-load isometric actions (iso-holds) during the inter-set recovery period versus RT that involves passive inter-set rest on muscular strength, muscular hypertrophy, and muscular endurance in resistance-trained men. Twenty-seven resistance-trained male volunteers were randomly assigned to either a traditional group (TRAD) that performed a hypertrophy-oriented RT routine with the rest intervals spent passively (n = 13) or to a group that supplemented traditional RT with iso-holds (ISO) for the working muscle group between each set (n = 14). Training for both routines consisted of three weekly sessions performed for …

Enhanced Tes And Tdcs Computational Models By Meninges Emulation, Jimmy Jiang, Dennis Q. Truong, Zeinab Esmaeilpour, Yu Huang, Bashar W. Badran, Marom Bikson

Publications and Research

Objective. Understanding how current reaches the brain during transcranial electrical stimulation (tES) underpins efforts to rationalize outcomes and optimize interventions. To this end, computational models of current flow relate applied dose to brain electric field. Conventional tES modeling considers distinct tissues like scalp, skull, cerebrospinal fluid (CSF), gray matter and white matter. The properties of highly conductive CSF are especially important. However, modeling the space between skull and brain as entirely CSF is not an accurate representation of anatomy. The space conventionally modeled as CSF is approximately half meninges (dura, arachnoid, and pia) with lower conductivity. However, the resolution …

Structure Of The Cell-Binding Component Of The Clostridium Difficile Binary Toxin Reveals A Di-Heptamer Macromolecular Assembly, Xingjian Xu, Raquel Godoy-Ruiz, Kaylin A. Adipietro, Christopher Peralta, Danya Ben-Hail, Kristeny M. Varney, Mary E. Cook, Braden M. Roth, Paul T. Wilder, Thomas Cleveland, Alexander Grishaev, Heather M. Neu, Sarah L. J. Michel, Wenbo Yu, Dorothy Beckett, Richard R. Rustand, Catherine Lancaster, John W. Loughney, Adam Kristopeit, Sianny Christantii, Jessica W. Olson, Alexander D. Mackerell, Amedee Des Georges, Edwin Pozharski, David J. Weber

Advanced Science Research Center

Targeting Clostridium difficile infection is challenging because treatment options are limited, and high recurrence rates are common. One reason for this is that hypervirulent C. difficile strains often have a binary toxin termed the C. difficile toxin, in addition to the enterotoxins TsdA and TsdB. The C. difficile toxin has an enzymatic component, termed CDTa, and a pore-forming or delivery subunit termed CDTb. CDTb was characterized here using a combination of singleparticle cryoelectron microscopy, X-ray crystallography, NMR, and other biophysical methods. In the absence of CDTa, 2 di-heptamer structures for activated CDTb (1.0 MDa) were solved at atomic resolution, including …

Exploring The Potential Of Nitric Oxide And Hydrogen Sulfide (Nosh)-Releasing Synthetic Compounds As Novel Priming Agents Against Drought Stress In Medicago Sativa Plants, Chrystalla Antoniou, Rafaella Xenofontos, Giannis Chatzimichail, Anastasis Christou, Khosrow Kashfi, Vasileios Fotopoulos

Publications and Research

Land plants are continuously exposed to multiple abiotic stress factors like drought, heat, and salinity. Nitric oxide (NO) and hydrogen sulfide (H2S) are two well-examined signaling molecules that act as priming agents, regulating the response of plants to stressful conditions. Several chemical donors exist that provide plants with NO and H2S separately. NOSH is a remarkable novel donor as it can donate NO and H2S simultaneously to plants, while NOSH-aspirin additionally provides the pharmaceutical molecule acetylsalicylic acid. The current study aimed to investigate the potential synergistic effect of these molecules in drought-stressed Medicago sativa L. plants by following a pharmacological …

The Whelming Sea, Sean Hanley

Theses and Dissertations

The Whelming Sea is a thirty-minute experimental documentary that reveals the moments of entanglement between three animals living along the Mid-Atlantic shoreline; curious humans, spawning horseshoe crabs, and migratory shorebirds. Working from the realm of multispecies ethnography, the film shifts the subjective positioning of the viewer between the human and nonhuman to suggest the complexity of our enmeshed experience. In the face of this current era of mass extinction, the film explores the limitations and poetic possibilities of scientific encounters with the lives of others.

Water In Your Neighbourhood: A Model For Implementing A Semester-Long Course-Based Undergraduate Research Project In Introductory Biology, Ana Lucia Fuentes, Maria Entezari

Publications and Research

Undergraduate biology education has changed over the past decade, incorporating an iterative and evidence-based approach. Many educational assessments have confirmed the effectiveness of integrating authentic research and open-ended inquiry into introductory biology courses, demonstrating a significant positive impact on students’ learning and attitude towards STEM majors. Despite these findings, only a handful of Biology instructors in 2-year colleges adopt this approach, and when adopted, most activities constitute a small fraction of these courses. Finding a feasible, sustainable, semester-long, and cost-effective strategy to incorporate authentic research in the curriculum which promotes integrated understanding of science and addresses socio-scientific issues, is a …

Cis-Regulatory Analysis Of Onecut1 Expression In Fate-Restricted Retinal Progenitor Cells, Sruti Patoori, Nathalie Jean-Charles, Ariana Gopal, Sacha Sulaiman, Sneha Gopal, Brian Wang, Benjamin Souferi, Mark Emerson

Publications and Research

Background: The vertebrate retina consists of six major classes of neuronal cells. During development, these cells are generated from a pool of multipotent retinal progenitor cells (RPCs) that express the gene Vsx2. Fate-restricted RPCs have recently been identified, with limited mitotic potential and cell fate possibilities compared to multipotent RPCs. One population of fate-restricted RPCs, marked by activity of the regulatory element ThrbCRM1, gives rise to both cone photoreceptors and horizontal cells. These cells do not express Vsx2, but co-express the transcription factors (TFs) Onecut1 and Otx2, which bind to ThrbCRM1. The components of the gene regulatory networks that control …

Biological Foundations I, Fardad Firooznia

Open Educational Resources

This is a syllabus for a first-semester introductory biology class, including reading links for current news articles related to the course topics as well as an OpenStax textbook.

Sediment Microbiomes Associated With Critical Habitat Of The Juvenile American Horseshoe Crab; Limulus Polyphemus, J. Petersen, Christina P. Colon, J. L. Joyner

Publications and Research

Plumb Beach, Brooklyn, New York in USA is an important horseshoe crab breeding and nursery ground that has experienced substantial anthropogenic influence, including pollution, erosion and subsequent restoration. Since little is known about the relationship between sediment microbial communities and juvenile horseshoe crab survival, next generation sequencing was used to characterize and compare the sediment microbiome of three distinct areas of Plumb Beach:- a tidal creek with abundant juveniles, East Beach with moderate number of juveniles, and West Beach- a highly disturbed area where juvenile crabs are rarely seen. The microbiome of juvenile crab intestinal content (both dissected gut content …

Analysis Of Adult Neural Retina Extracellular Vesicle Release, Rna Transport And Proteomic Cargo, Jason Mighty, Jing Zhou, Alberto Benito-Martin, Sami Sauma, Samer Hanna, Onyekwere Onwumere, Cui Shi, Martin Muntzel, Moira Sauane, Michael Young, Henrik Molina, Dianne Cox, Stephen Redenti

Publications and Research

PURPOSE. Extracellular vesicles (EVs) contain RNA and protein cargo reflective of the genotype and phenotype of the releasing cell of origin. Adult neural retina EV release, RNA transfer, and proteomic cargo are the focus of this study.

METHODS. Adult wild-type mouse retinae were cultured and released EV diameters and concentrations quantified using Nanosight. Immunogold transmission electron microscopy (TEM) was used to image EV ultrastructure and marker protein localization. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze retinal cell transcripts present in EVs. Super-resolution microscopy was used to image fluorescent (green) RNA and (red) lipid membrane labeled EVs, released …

A Tale Of Winglets: Evolution Of Flight Morphology In Stick Insects, Yu Zeng, Connor O'Malley, Sonal Singhal, Faszly Rahim, Sehoon Park, Xin Chen, Robert Dudley

Publications and Research

The evolutionary transition between winglessness and a full-winged morphology requires selective advantage for intermediate forms. Conversely, repeated secondary wing reductions among the pterygotes indicates relaxation of such selection. However, evolutionary trajectories of such transitions are not well-characterized. The stick insects (Phasmatodea) exhibit diverse wing sizes at both interspecific and intersexual levels, and thus provide a system for examining how selection on flight capability, along with other selective forces, drives the evolution of flight-related morphology. Here, we examine variation in relevant morphology for stick insects using data from 1,100+ individuals representing 765 species. Although wing size varies along a continuous spectrum, …

Bioenergetic Modulation Of Retinal Progenitor Cell Glycolysis To Drive Invasion For Photoreceptor Replacement, Jei Espinal

Theses and Dissertations

Given the limited regenerative capacity of the mammalian retina, cell-replacement strategies are necessary. To replace photoreceptors lost to disease or trauma and restore visual function, laboratories throughout the world are researching photoreceptors replacement strategies using subretinal transplantation of retinal progenitor cells (RPCs). A major obstacle to the advancement of photoreceptor cell-replacement strategies includes low rates of invasion and integration of transplanted cells into the host retina. Currently, there is a limited understanding of how RPC glycolysis may facilitate invasion. To further understand RPC glycolysis-driven invasion, the current investigation involved the bioenergetic modulation RPCs for glycolysis analysis and invasion modeling. The …

Sinorhizobium Meliloti Changes Motility Phenotypes In The Presence Of Serum, Eris K. Bisal

Theses and Dissertations

Sinorhizobium meliloti is a nitrogen-fixing flagellated soil bacterium that engages in a mutual symbiotic relationship with the legume Medicago sativa. Using its flagella, S. meliloti is chemotactic in response to varying environmental cues thereby directed to a target, which is typically the root hairs of M. sativa. Lu et al, 2012 suggested that a signal from the plant can switch S. meliloti from a free-living flagellated microbe to a host-invading non-flagellated microbe, although this signal has not been identified. This switch is thought to occur inside curled root hairs of the plant, and after becoming non-flagellated, S. …

Antibacterial, Antifungal, Antioxidant Activity And Polyphenol Content Of Aerial Parts And Bulbs Of Allium Schugnanicum., Saidbeg Satorov, F. Mirzoeva, Sh. Kurbonbekova, Sh. Satorov, M. Vakhidova, Vyacheslav Dushenkov

Publications and Research

Objective: То study of antibacterial, antifungal and antioxidant activity, and content of polyphenols in the bulb and aerial parts of an endemic species of onion A. schugnanicum. Methods: An ethanol-based extract was prepared from fresh plants. Total polyphenolic content (Folin) and ABTS antioxidant capacity assays were used to characterized extracts. Extracts obtained from bulbs, peduncle, and seeds demonstrated antibacterial activity against the reference Staphylococcus aureus (ATCC 4929), Pseudomonas aeruginosa (ATCC 4930) and Klebsiella pneumoniae (ATCC 4927) strains, as well as against the hospital strains of the same types of bacteria, i.e. strains isolated from inpatient surgical patients. Results: The study …

Ecosystem Health In Guánica Bay And La Parguera, Puerto Rico: Remote Sensing Of Ocean Color And Metal Analysis Of Coral Tissue And Surficial Sediments, Jahnelle Howe

Dissertations and Theses

Guánica Bay is an estuary located in southwest Puerto Rico, with a coral reef ecosystem at its periphery. This ecosystem is affected by sediments, nutrients, and contaminants from the watershed through the Bay and into the offshore water. This project evaluates Guánica Bay and La Parguera coastal areas through remote sensing and chemical analysis to assess coastal ecosystem health. The concentration of metals in two coral species and their associated surface sediments was were analyzed by X-ray fluorescence (XRF) and Direct Mercury Analyzer (DMA- 80). Ocean color remote sensing was used to estimate nutrient inputs and phytoplankton biomass through chlorophyll- …