Life Sciences Commons^™

Lim Protein Ajuba Directly Interacts With Replication Protein A To Prevent Atr Dna Damage Response, Sandy Wan Shan Fowler

Dissertations, Theses, and Capstone Projects

Integrity of the human genome is essential for viability and proliferation of human cells. Intrinsic (endogenous replication stress) or extrinsic (UV, chemotherapy drugs) agents threaten the stability of the genome by generation of single stranded (ss) DNA or double stranded (ds) DNA breaks. The DNA damage response (DDR) pathways are conserved in evolution and constitute systems that perform the surveillance, signaling, and repair of the damage in the nucleus. Unchecked and accumulation of DNA damage can lead to deleterious effects such as replication fork collapse, chromosome fusion and breakage. The dysregulations of DNA damage response pathways are hallmarks of tumorigenesis. …

Pharmacological Antagonism And The Olfactory Code, Mihwa Na

Dissertations, Theses, and Capstone Projects

Mammals can detect and discriminate uncountable odors through their odorant receptors. To accommodate the countless and diverse odors, exceptionally large numbers of odorant receptor (OR) genes are expressed in mammals. In addition, the mammals utilize a combinatorial code, where an odorant molecule can activate multiple ORs; an OR also responds to a set of multiple odorants. In nature, an odor is often a complex mixture of multiple odorant molecules. The combination of the ORs activated by each constituent generates the unique olfactory code for the particular odor.

Some odorants can antagonize select ORs, as discussed in Chapter 1. An antagonist …

Structural And Biochemical Studies Of The Dna Replication Initiation Mechanism Of The Second Chromosome Of Vibrio Cholerae, Natalia Orlova

Dissertations, Theses, and Capstone Projects

Transmission of genetic information through DNA replication is one of the key processes for any living organism. Despite the extensive effort put into studies of the mechanism of DNA replication, the understanding of the process on the molecular level is still incomplete. Specifically the molecular details of the very first events of DNA replication initiation are not sufficiently understood.

The majority of bacteria possess a single circular chromosome, and in order to initiate DNA replication these organisms utilize a conserved system, consisting of a specific DNA sequence - replication origin, called oriC, and replication initiator protein DnaA. However, bacteria …

Regulation Of The Amyloid Precursor Protein By Prostaglandin J2, A Mediator Of Inflammation: Relevance To Alzheimer’S Disease, Teneka L. Jean-Louis

Dissertations, Theses, and Capstone Projects

Inflammation plays a major role in Alzheimer’s disease (AD). Investigating how specific mediators of inflammation contribute to neurodegeneration in AD is crucial. Our studies focused on cyclooxygenases, which are key enzymes in inflammation and highly relevant to AD. Cyclooxygenases (COX -1, constitutive; COX-2, inducible) have emerged as important determinants of AD pathogenesis and progression. COX-2 is highly induced in AD, correlating with AD severity, and COX-1 is also involved in AD. Cyclooxygenases are the rate-limiting enzymes that convert arachidonic acid into prostaglandins (PGs), the principal mediators of CNS neuroinflammation.

The overall GOAL of these studies was to address the mechanisms …

The Role Of Glutamate Neurotransmission In The Ventral Tegmental Area In The Expression Of Conditioned Approach Learning, Priscila Hachimine-Merli

Dissertations, Theses, and Capstone Projects

Conditioned stimuli (CSs) come to function as CSs by acquiring the capacity to activate the same mesocorticolimbic dopamine (DA) neurons activated by primary rewards, producing conditioned activation of these neurons and their associated motivational states. This model stipulates that CSs activate mesocorticolimbic DA systems through the activation of glutamate receptors on DA neurons in the ventral tegmental area (VTA). We tested the hypothesis that glutamate receptor stimulation in the VTA is necessary for the expression of conditioned approach. Rats were tested in a conditioned approach protocol that consisted of 7 consecutive conditioning sessions (light presentations and food were paired), one …

The Role Of Pitx Proteins In Early Xenopus Development, Ye Jin

Dissertations, Theses, and Capstone Projects

Embryos of the African clawed frog Xenopus laevis are widely used for the study of early vertebrate development. The cement gland, which secrets mucus to help tadpoles attach to solid supports and live in relative safety, has long been used as a model to study the interplay between cell signaling pathways and transcription factors. It has been proposed that an intermediate level of Bone Morphogenetic Protein (BMP) signaling is essential for cement gland formation. In addition, several transcription factors have been linked to cement gland development. Among them, the homeodomain proteins Pitx1 and the closely related Pitx2c can generate ectopic …

The Nucleus Accumbens Core Dopamine D1 And Glutamate Ampa/Nmda Receptors Play A Transient Role In The Performance Of Pavlovian Approach Behavior, Veronica Dobrovitsky

Dissertations, Theses, and Capstone Projects

The role of the nucleus accumbens core (NAc core) continues to be redefined with newly acquired data on neurochemical mechanisms mediating the learning and performance of behavior. Previous empirical data showed that dopamine transmission at the D1 receptor (D1R) plays a transient role in the expression of learned Pavlovian approach behavior. Here we show that, prior to overtraining, dopamine activity at D1Rs specifically within the NAc core is critical for the performance of approach behavior elicited by the recently-acquired reward-paired cue. Blockade of D1Rs in the NAc core, but not the dorsomedial striatum or NAc shell, disrupted approach responses during …

Comparative Phylogeographic, Population Genomic, And Selection Inference With Development Of Hierarchical Co-Demographic Models, Alexander Xue

Dissertations, Theses, and Capstone Projects

Comparing demographic histories across assemblages of populations, species, and sister pairs has been a focus in phylogeography since its inception. Initial approaches utilized organelle genetic data and involved qualitative comparisons of genetic patterns for evaluating hypotheses of shared evolutionary responses to past environmental changes. This endeavor has progressed with coalescent model-based statistical techniques and advances in next-generation sequencing, yet there remains a need for methods that can analyze aggregated genomic-scale data from non-model organisms within a unified framework that considers individual taxon uncertainty and variance. To this end, the aggregate site frequency spectrum (aSFS), an expansion of the site frequency …

Climate-Driven Habitat Shifts In South America: Biogeography, Historical Demography, And Population Genomics Of Anole Lizards, Ivan Prates

Dissertations, Theses, and Capstone Projects

Shifts in the geographic distribution of habitats over time can promote dispersal and vicariance, thereby influencing large-scale biogeographic patterns and ecological processes. The establishment of corridors of suitable habitat across previously disjunct yet ecologically similar regions has been widely linked to climate change over time. Such climate-mediated habitat changes may have played a key role in the assembly of tropical biotas, including those of Amazonia and the coastal Atlantic Forest in South America, two of the most diverse ecosystems on Earth. The history of biogeographic associations between tropical rainforest habitats in response to former climatic shifts, as well as their …

Song Rhythm Development In Zebra Finches, Julia Hyland Bruno

Dissertations, Theses, and Capstone Projects

This dissertation investigates song-rhythm learning in songbirds. Songbirds have been studied extensively in mechanistic investigations into the sensorimotor underpinnings of the cultural transmission of learned vocalizations. While several studies identified forebrain song-system neurons that generate rhythmic song patterns, we know little about how song rhythms are learned. The first part of the dissertation describes methods for detecting and analyzing birdsong rhythm patterns, and demonstrates their utility for identifying the role of song rhythms in social interactions. Results suggest that rhythm plasticity in zebra finch song may provide a potential vehicle for communication. Controlled song-learning experiments further found that developing zebra …

The Role Of T-Box Proteins In Vertebrate Germ Layer Formation And Patterning, Sushma Teegala

Dissertations, Theses, and Capstone Projects

All of the tissues in triploblastic organisms, with the exception of the germ cells, arise from the three germ layers, ectoderm, mesoderm and the endoderm. The identification of the genes that underlie the differentiation of these layers is crucial to our understanding of development. T-box family proteins are DNA-binding transcriptional regulators that play important roles during germ layer formation in the early vertebrate embryo. Well-characterized members of this family, including the transcriptional activators Brachyury and VegT, are essential for the proper formation of mesoderm and endoderm, respectively. To date, T-box proteins have not been shown to play a role in …

A Combined Computational Strategy Of Sequence And Structural Analysis Predicts The Existence Of A Functional Eicosanoid Pathway In Drosophila Melanogaster, Michael Scarpati

Dissertations, Theses, and Capstone Projects

With increased understanding of their roles in signal transduction and metabolism, eicosanoids have emerged as important players in human health and disease. Mammalian prostanoids and related lipid mediators perform varied functions in different tissues and organs. Synthesized through the oxygenation of C20 polyunsaturated fatty acids, mammalian eicosanoids are both pro- and anti-inflammatory. The physiological contexts in which eicosanoid family members act at the cellular level are not well understood. In this study, we examined whether the genome of Drosophila melanogaster, a powerful model for innate immunity and inflammation, codes for the enzymes required for eicosanoid biosynthesis. We report the …

The Role Of Nucleolin Phosphorylation By Ck2 In Regulating Cellular Fate Under Normal And Stress Conditions, Shu Xiao

Dissertations, Theses, and Capstone Projects

Nucleolin (NCL or C23) is an abundant genotoxic stress-responsive RNA binding phosphoprotein. NCL constitutes 10% of total nucleolar protein that has functions in multiple biological processes, including ribosome biogenesis, DNA/RNA metabolism, cellular response to DNA damage, cell growth, proliferation and death. In this dissertation, I elucidate the role of nucleolin phosphorylation by casein kinase 2 (CK2) in controlling cellular fate by regulating p53 checkpoint under normal and stressed conditions. First, I demonstrate that the six consensus CK2 sites on the N-terminus of NCL are important for cell survival and proliferation. Expression of CK2 phosphorylation-deficient NCL mutant leads to dominant negative …

Computational Investigation Of The Pore Formation Mechanism Of Beta-Hairpin Antimicrobial Peptides, Richard Lipkin

Dissertations, Theses, and Capstone Projects

β-hairpin antimicrobial peptides (AMPs) are small, usually cationic peptides that provide innate biological defenses against multiple agents. They have been proposed as the basis for novel antibiotics, but their pore formation has not been directly observed on a molecular level. We review previous computational studies of peptide-induced membrane pore formation and report several new molecular dynamics simulations of β-hairpin AMPs to elucidate their pore formation mechanism. We simulated β-barrels of various AMPs in anionic implicit membranes, finding that most of the AMPs’ β-barrels were not as stable as those of protegrin. We also performed an optimization study of protegrin β-barrels …

Insight Into The Interaction Between The Peroxisome Proliferator-Activated Receptor Gamma (Pparγ) And Adipocyte Fatty Acid-Binding Protein (A-Fabp), Qian Wang

Dissertations, Theses, and Capstone Projects

The Adipocyte Fatty Acid-Binding Protein (AFABP) is mainly expressed in fat cells. It can bind fatty acids and other lipophilic substances such as eicosanoids and retinoids. The peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor protein that requires ligand binding to regulate the specific gene transcription. PPARγ is expressed at extremely high levels in adipose tissue, macrophages, and the large intestine, where it controls lipid adipogenesis and energy conversion. Moreover, it has been found that AFABP and PPARγ can form a complex in vivo. It is proposed that AFABP carries the ligand and enters into the nucleus where it …

Cognitive And Neurobiological Degeneration Of The Mental Lexicon In Primary Progressive Aphasia, Jet M. J. Vonk

Dissertations, Theses, and Capstone Projects

The ease with which we use the thousands of words in our vocabulary stands in stark contrast to our difficulty establishing how they are organized in our mind and brain. The breakdown of language due to cortical atrophy in primary progressive aphasia (PPA) creates conditions to study this organization at a cognitive and neurobiological level in that the three variants of this disease, namely non-fluent, logopenic, and semantic PPA, each bear their own signature of language-specific decline and cortical atrophy. As the impaired regions in each variant are linked to different lexical and semantic attributes of words, lexical decision performance …

Mutagenesis Of Human Alpha-Galactosidase A For The Treatment Of Fabry Disease, Erin Stokes

Dissertations, Theses, and Capstone Projects

Fabry disease is an X-linked lysosomal storage disorder caused by the deficiency of the enzyme, α-galactosidase A, which results in the accumulation of the lipid substrate. This accumulation results in obstruction of blood flow in patients and early demise at approximately 40-60 years of age. There is currently only one FDA approved treatment (Fabrazyme) classified as an enzyme replacement therapy. However, approximately 88% of patients experience a severe immune response that, rarely, can be fatal and is a huge cost burden at average $250,000 a year per patient. The structure of α-galactosidase A has been previously determined to be a …

Ecologies Of Embodied Minds Embedded: Radical Romantic Perspectives On Architectures Of Technology, Sharmaine Browne

Dissertations, Theses, and Capstone Projects

This dissertation explores Romantic responses to the role of architectural technologies in the development of material being, consciousness, and culture by applying a critical approach in which I combine radical embodied cognitive theory, ecocritical perspectives, and a phenomenological lens to select Romantic texts written from 1789 to 1884 in response to industrial modernity. While scholarship has thoroughly explored technology as a cultural force which inevitably shapes consciousness, I propose that a slight shift of emphasis from technology’s external influence to the material internalization of its influence allows for new perspectives—particularly in light of recent proposals in cognitive philosophy which assert …

Modulation Of The Sodium/Potassium Atpase Function And Expression By Transcranial Direct Current Stimulation Of The Right Sensorimotor Cortex In Mice, Salim Bendaoud

Dissertations, Theses, and Capstone Projects

Direct current stimulation is used as a noninvasive therapeutic technique to enhance motor recovery following stroke, and to improve cognitive functions. This technique also showed promising results in the treatment of depression, schizophrenia, and multiple sclerosis. Transcranial direct current stimulation has been proven to cause a polarization (depolarization or hyperpolarization) of the target tissues depending on the polarity of the current and cell orientation. Because of the induced polarization, the spontaneous activity of the neurons is further affected. With exception to this electrophysiological effect, the overall biological mechanisms of transcranial direct current stimulation on the underlying tissues remain largely unknown. …

Retinal Progenitor Cell, Induced Pluripotent Stem Cell, And 3d Mini Retina Derived Extracellular Vesicles Contain Transcription Factors, Microrna And Protein Associated With Potency And Development, Jing Zhou

Dissertations, Theses, and Capstone Projects

Extracellular vesicles (EVs) have emerged as a novel cell-to-cell communication mechanism in recent years. EVs are membrane-covered cell fragments released into the extracellular environment by all cell types in the normal physiological and pathological conditions. These membranous extracellular organelles include exosomes (30-100 nm) and microparticles (100-1000 nm), which are believed to play a pivotal role in intercellular communication. EVs represent the way for intercellular transfer of proteins and RNAs. By transfer of genetic materials, EVs are involved in reprogramming and tissue repair. We predict that during retinal development, retinal progenitor cells release EVs containing temporally expressed mRNA, proteins and miRNA, …

Walking As Ontological Shifter: Thoughts In The Key Of Life, Bibi (Silvina) Calderaro

Dissertations, Theses, and Capstone Projects

With walking as ontological shifter I pursue an alternative to the dominant modernist episteme that offers either/or onto-epistemologies of opposition and their reifying engagements. I propose this type of walking is an intentional turning towards a set of radical positions that, as integrative aesthetic and therapeutic practice, brings multiplicity and synchronicity to experience and being in an expanded sociality. This practice facilitates the conditions of possibility for recurring points of contact between the interiority perceived as ‘body’ and the exteriority perceived as ‘world.’ While making evident the self’s at once incoherence with it-self, it opens to a space beyond the …

Potential Modifications To Enzyme Replacement Therapy In Anderson-Fabry Disease, Mariam Meghdari

Dissertations, Theses, and Capstone Projects

Mutations in the GLA gene that encodes the lysosomal enzyme α-galactosidase A (αGal) result in the sphingolipidoses named Fabry disease. This enzymatic defect is inherited as an X-linked recessive disorder and is associated with a progressive deposition of glycosphingolipids, including globotriaosylceramide (GB3), galabioasylceramide, and blood group B substance in the cell. In affected males, and in some females, this leads to early death due to occlusive disease of the heart, kidney, and brain. This disease is currently treated by infusions of αGal, prolonging patients’ lives but producing antibodies against the enzyme reducing the treatment efficacy. Treatment also causes numerous and …

Distribution And Activation Of Catecholaminergic Neurons In The Brain Of Male Plainfin Midshipman Fish: Divergence In Behavior And Reproductive Phenotype, Zachary Ghahramani

Dissertations, Theses, and Capstone Projects

The plainfin midshipman fish, Porichthys notatus, provides an excellent opportunity for delimiting the influence of neurochemical content on vertebrate vocal behavior, in part because the production and recognition of social-acoustic signals is vital to their reproductive behavior. There are two distinct reproductive male morphs that follow divergent developmental trajectories with corresponding alternative reproductive tactics: type I males are the territorial/nesting morph that vocally court females during the summer breeding season while type II males do not court females, but instead sneak spawn in competition with type I males. Catecholaminergic neurons, which synthesize and release the neurotransmitters dopamine or noradrenaline, …

A Realization Of Modernity: Case Studies In Connectivity And Time, Mari Gorman

Dissertations, Theses, and Capstone Projects

My stated goal in applying to The Graduate Center was to explore my previous research in diverse fields of study. This research, the result of a formal investigation of acting, was and still is centrally focused on the subject of relationship itself, relationships being what actors create. In pursuit of a greater understanding of the essential nature of relationship in practical terms, a self-organizing complex system that constitutes universal relationship was unexpectedly discovered. As such, this system has been shown to offer solutions to many outstanding problems in diverse areas of study. The Liberal Studies program track, Approaches to Modernity …

A Combinatorial Framework For Multiple Rna Interaction Prediction, Syed Ali Ahmed

Dissertations, Theses, and Capstone Projects

The interaction of two RNA molecules involves a complex interplay between folding and binding that warranted recent developments in RNA-RNA interaction algorithms. However, biological mechanisms in which more than two RNAs take part in an interaction also exist.

A typical algorithmic approach to such problems is to find the minimum energy structure. Often the computationally optimal solution does not represent the biologically correct structure of the interaction. In addition, different biological structures may be observed, depending on several factors. Furthermore, scoring techniques often miss critical details about dependencies within different parts of the structure, which typically leads to lower scores …

Morphogenesis And Growth Driven By Selection Of Dynamical Properties, Yuri Cantor

Dissertations, Theses, and Capstone Projects

Organisms are understood to be complex adaptive systems that evolved to thrive in hostile environments. Though widely studied, the phenomena of organism development and growth, and their relationship to organism dynamics is not well understood. Indeed, the large number of components, their interconnectivity, and complex system interactions all obscure our ability to see, describe, and understand the functioning of biological organisms.

Here we take a synthetic and computational approach to the problem, abstracting the organism as a cellular automaton. Such systems are discrete digital models of real-world environments, making them more accessible and easier to study then their physical world …

Trypanosome Lytic Factor Mediated Immunity Against Leishmania Sp., Jyoti Pant

Dissertations, Theses, and Capstone Projects

Trypanosome Lytic Factor (TLF) is an innate immunity complex that was originally discovered to protect against African Trypanosomes. The major components of TLF are Apolipoprotein A1 (APOA1), Apolipoprotein L1 (APOL1) and HPR (Haptoglobin Related Protein), where APOL1 is necessary and sufficient for trypanolysis. Recently we have shown that TLF ameliorates infections by cutaneous Leishmania species. Here we investigated the effect of different primate and human TLF against different Leishmania sp. Our result shows that TLF kills metacyclic promastigotes of cutaneous Leishmania sp. within immune cells such as neutrophils and macrophages by two different mechanism. Using transiently transfected and germline transgenic …

Modulation Of Spasticity By Trans-Spinal Direct Current Stimulation In Animals With Spinal Cord Injury, Wagdy Mekhael

Dissertations, Theses, and Capstone Projects

Central nervous system injuries usually produce motor impairments that are exacerbated by pathologically altered muscle tone. Abnormal muscle tone interferes with voluntary movement and is associated with loss of dexterity. Prior work in our laboratory demonstrated that 30-second trans-spinal direct current (DC) stimulation can temporarily modify muscle tone in anesthetized spastic mice after spinal cord injury (SCI). These experiments described DC-induced muscle tone responses to be polarity-dependent. That is, anodal stimulation (current passed from the lumbar spine to sciatic nerve) decreased muscle tone, and cathodal stimulation (current passed from the sciatic nerve to the lumbar spine) increased it. The present …

Between Speech & Song: Clarifying The Sprechstimme Of Schoenberg's Pierrot Lunaire, Sara M. Paar

Dissertations, Theses, and Capstone Projects

Since its creation, the technique of Sprechstimme has fascinated the audiences, performers, and composers of twentieth century music. What is it? How is it done? How should it be notated? At the fore of investigations into these questions has been Arnold Schoenberg’s Pierrot lunaire, the work in which Schoenberg debuted this new technique. Much has been written in regard to Schoenberg’s creation and use of Sprechstimme, as well as his own exploration of the speech/song continuum. Composers, conductors, and performers have all tried to make sense of the notation, instructions, and performances Schoenberg left behind. Despite this, confusion, …

Ecology, Evolution, And Sexual Selection In The Invasive, Globally Distributed Small Indian Mongoose (Urva Auropunctata), M. Aaron Owen

Dissertations, Theses, and Capstone Projects

Introduced species provide rare opportunities to test evolutionary hypotheses in situ by creating so-called natural experiments. Natural experiments are situations in nature that resemble laboratory studies by allowing for comparisons of a “control” group (i.e., a species’ native range) with “experimental” groups (i.e., a species’ introduced range). In particular, introduced animals allow us to investigate evolutionary dynamics in complex, long-lived organisms in ways that would otherwise be impossible in a laboratory setting. One such introduced animal is the small Indian mongoose (Urva auropunctata, formerly Herpestes auropunctatus). Native to South Asia, the small Indian mongoose’s introduction to more …