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Full-Text Articles in Life Sciences
Spontaneity And Precision In The Drosophila Central Nervous System, Bennett Ferris
Spontaneity And Precision In The Drosophila Central Nervous System, Bennett Ferris
Student Theses and Dissertations
Many organisms that can locomote change their navigational strategies depending upon behavioral context. During foraging or exploration, for instance, many animals navigate by interspersing straight runs with turns whose direction and frequency may originate, at least at times, from largely stochastic processes. Conversely, during goal-directed navigation, animals may use stored heading and distance signals to travel efficiently to a desired location. This thesis explores the circuitry underlying these disparate navigational strategies in Drosophila. I first show that normal synaptic transmission in a genetically specified population of neurons is necessary for one to observe an appreciable rate of spontaneous flight turns …
On The Interactions Of Augmin With Microtubules And The Mechanics Of The Cross-Linker Prc1, Alejandro Dottore
On The Interactions Of Augmin With Microtubules And The Mechanics Of The Cross-Linker Prc1, Alejandro Dottore
Student Theses and Dissertations
Cell division in eukaryotes requires the assembly and maintenance of a structure, the bipolar spindle, self-organized from microtubules and their associated proteins. A multitude of components have been identified to be involved in this organization, and solving the combinatorial of the conditions that lead to the specific set of configurations present in vivo remains an open question. This thesis presents reconstitutions from purified components used to study aspects of microtubule self-organization: first, the microtubule-nucleation-related augmin octameric complex was assessed at a single-molecule interaction level with microtubules; second, the cross-linker PRC1's frictional response resisting motion between two microtubule filaments was analyzed …
Neural Mechanisms That Control An Innate Foraging Behavior In Caenorhabditis Elegans, Alejandro Lopez-Cruz
Neural Mechanisms That Control An Innate Foraging Behavior In Caenorhabditis Elegans, Alejandro Lopez-Cruz
Student Theses and Dissertations
The ability to efficiently locate food is critical for survival. Thus, animals modify their foraging patterns based on recent experience and current conditions to increase their likelihood of finding food. One highly conserved foraging strategy is local search, an intensive exploration over several minutes of the region where food resources were last encountered. As time since the last food encounter passes, animals transition to global search strategies to explore distant areas. The local-to-global search foraging pattern has been observed in fish, reptiles, insects, birds, and mammals, yet few studies ask how an animal’s brain generates this ancient behavior. Here, I …
Modeling Alzheimer's Disease Using Crispr/Cas9 Gene Editing And Induced Pluripotent Stem Cells Reveals Conserved Cellular Mechanisms, Dylan Kwart
Student Theses and Dissertations
Alzheimer’s disease (AD) is the most common cause of dementia worldwide and a leading cause of death in the United States. Rare cases of autosomal dominant familial AD (fAD) result from genetic mutations in three key genes: amyloid precursor protein (APP), and two APP processing-related genes (presenilin-1 (PSEN1), and presenilin-2 (PSEN2)), supporting the theory that altered APP metabolism is a central cause of AD. However, which product of APP metabolism is causal remains a matter of investigation. A probable source of this lack of understanding stems from the poor disease model systems that have been utilized in the field for …
In Vitro, In Vivo, And In Silico Studies Of Reticulospinal Circuits And Generalized Arousal, Adele Bubnys
In Vitro, In Vivo, And In Silico Studies Of Reticulospinal Circuits And Generalized Arousal, Adele Bubnys
Student Theses and Dissertations
Generalized arousal (GA) is a fundamental force in the nervous system that alerts an individual to abrupt changes in its environment. A state of high GA is operationally defined by increases in an animal’s a.) locomotor output, b.) responsiveness to sensory stimuli, and c.) emotional reactivity. Previous studies have identified the nucleus gigantocellularis (NGC), a small group of large-bodied neurons in the hindbrain reticular formation, as a potential neuronal substrate for GA. These neurons are responsive to a wide range of sensory modalities and have diverse projections that target both forebrain areas and motor effectors directly within the spinal cord, …
Non-Coding Rna Features Critical To The Replication Of Hiv-1, Matthew A. Takata
Non-Coding Rna Features Critical To The Replication Of Hiv-1, Matthew A. Takata
Student Theses and Dissertations
The HIV-1 genome contains RNA sequences and structures that control many aspects of viral replication including, but not limited to transcription, splicing, nuclear export, translation, packaging and reverse transcription. Despite this extensive existing catalogue of RNA sequences that are critical to its replication, chemical probing and targeting mutagenesis studies suggest that the HIV-1 genome may contain many more RNA elements of unknown important function. To determine whether there are additional, undiscovered cis-acting RNA elements in the HIV-1 genome that are important for viral replication, we conducted a global synonymous mutagenesis experiment. Sixteen mutant proviruses containing clusters of ~50 to ~200 …
Sensory Coding And Olfactory Integration In Caenorhabditis Elegans, May Dobosiewicz
Sensory Coding And Olfactory Integration In Caenorhabditis Elegans, May Dobosiewicz
Student Theses and Dissertations
Animals must sense their external environments to guide meaningful behavior. The nematode Caenorhabditis elegans, for example, uses volatile cues to navigate toward food from a distance. How does an animal integrate the olfactory information from its environment? Here, I ask how multiple sensory neurons drive and shape one interneuron’s activity. C. elegans senses several odors, including the bacterial metabolite diacetyl, using the AWA sensory neurons. AWA forms chemical and electrical synapses onto several interconnected interneurons, which contribute to chemotaxis toward attractive odors like diacetyl. One AWA target is the interneuron AIA, which is connected to AWA via a putative electrical …
The Role Of Zmynd8 In Immunoglobulin Class Switch Recombination, Daniel Benjamin Rosen
The Role Of Zmynd8 In Immunoglobulin Class Switch Recombination, Daniel Benjamin Rosen
Student Theses and Dissertations
Class switch Recombination (CSR) also known as Immunoglobulin (Ig) Class switching is a genomic recombination/deletion reaction that diversifies the effector component of the antibody response but preserves antigen specificity. CSR is initiated by the enzyme activation induced cytidine deaminase (AID), which produces nucleotide mismatches in actively transcribed immunoglobulin heavy chain (Igh) switch donor and acceptor DNA. The 3’ Regulatory Region (3’RR), a prototypical super-enhancer located at the 3’ of the Igh locus, is essential for acceptor switch region transcription, but the mechanism by which it regulates this process is not well defined. After targeting by AID, nearby mismatches in the …
Center Manifold Dynamics In Randomly Coupled Oscillators And In Cochlea, Dimitrios Moirogiannis
Center Manifold Dynamics In Randomly Coupled Oscillators And In Cochlea, Dimitrios Moirogiannis
Student Theses and Dissertations
In dynamical systems theory, a fixed point of the activity is called nonhyperbolic if the linearization of the system around the fixed point has at least one eigenvalue with zero real part. The center manifold existence theorem guarantees the local existence of an invariant subspace of the activity, known as a center manifold, around nonhyperbolic fixed points. A growing number of theoretical and experimental studies suggest that neural systems utilize dynamics on center manifolds to display complex, nonlinear behavior and to flexibly adapt to wide-ranging sensory input parameters. In this thesis, I will present two lines of research exploring nonhyperbolicity …
Dopamine And The Temporal Dependence Of Learning And Memory, Annie Handler
Dopamine And The Temporal Dependence Of Learning And Memory, Annie Handler
Student Theses and Dissertations
Animal behavior is largely influenced by the seeking out of rewards and avoidance of punishments. Positive or negative reinforcements, like a food reward or painful shock, impart meaningful valence onto sensory cues in the animal’s environment. The ability of animals to form associations between a sensory cue and a rewarding or punishing reinforcement permits them to adapt their future behavior to maximize reward and minimize punishments. Animals rely on the timing of events to infer the causal relationships between cues and outcomes –– sensory cues that precede a painful shock in time become associated with its onset and are imparted …
The Role And Control Of Wnt Signalling In An Hesc Model Of Human Primitive Streak, Iain Martyn
The Role And Control Of Wnt Signalling In An Hesc Model Of Human Primitive Streak, Iain Martyn
Student Theses and Dissertations
In amniotes, gastrulation is marked by the creation of the primitive streak (PS) and is largely controlled by WNT, BMP, and ACTIVIN/NODAL signalling. Despite detailed characterization in model organisms, the human PS and the role these pathways play in its formation and patterning remains a mystery. In this work I focused on understanding the role and control of the WNT pathway in human PS development. Due to the ethical limitations of working with human embryos, I used an in vitro human embryonic stem cell (hESC) micropatterned “gastruloid” system. I first showed that in the human PS there is a conserved …
Generation Of Memory Of Infection During The Crispr-Cas9 Immune Response, Robert Heler
Generation Of Memory Of Infection During The Crispr-Cas9 Immune Response, Robert Heler
Student Theses and Dissertations
Clustered regularly interspaced short palindromic repeat (CRISPR) loci and their associated (Cas) proteins provide adaptive immunity against viral attack in prokaryotes. Upon infection, short phage sequences known as spacers integrate between CRISPR repeats and are transcribed into small RNA molecules that guide the Cas9 nuclease to the viral targets (protospacers). Streptococcus pyogenes Cas9 cleavage of the viral genome requires the presence of a 5′-NGG-3′ protospacer adjacent motif (PAM) sequence immediately downstream of the viral target. Before my graduate work, it was not known whether and how viral sequences flanked by the correct PAM are chosen as new spacers. My work …
Molecular Characterization Of Novel Mutations In Fanconi Anemia Patients, Kimberly Rickman
Molecular Characterization Of Novel Mutations In Fanconi Anemia Patients, Kimberly Rickman
Student Theses and Dissertations
Fanconi anemia (FA) is a rare disorder that is characterized by bonemarrow failure in the first decade of life, developmental abnormalities, and predisposition to malignancies. The majority of patients have mutations in one of the 22 known FA genes, while a small number of patients have not been assigned to a complementation group. FA proteins are required for the proper repair of DNA interstrand crosslinks (ICL), a deleterious type of DNA damage that covalently binds DNA strands. We have used Whole Exome Sequencing (WES) in conjunction with cell-based assays to determine disease-causing mutations in a subset of patients enrolled in …
Gpcr Activation Of The G Protein-Gated Inward-Rectifier Potassium Channel, Kouki Touhara
Gpcr Activation Of The G Protein-Gated Inward-Rectifier Potassium Channel, Kouki Touhara
Student Theses and Dissertations
Heart rate is tightly regulated by the combined effects of the sympathetic and parasympathetic branches of the autonomic nervous system. These two branches control heart rate by stimulating different G protein-coupled receptors (GPCRs), which in turn activate ion channels that modify the electrical properties of cardiac pacemaker cells. Sympathetic stimulation accelerates heart rate through activation of beta-adrenergic receptors (βARs), which open excitatory ion channels through the stimulatory G protein (Gαs) pathway. Parasympathetic stimulation slows heart rate through activation of the muscarinic acetylcholine receptor M2 (M2Rs), which inhibits the effect of sympathetic stimulation through the inhibitory G protein (Gαi) pathway. M2Rs …
A Stress-Induced Trna Depletion Response Mediates Codon-Based Translational Repression And Growth Suppression, Doowon Huh
Student Theses and Dissertations
Eukaryotic transfer RNAs (tRNAs) can become fragmented upon various cellular stresses, generating tRNA-derived RNA fragments (tRFs). Though this process has been observed for numerous cellular stresses and in many species ranging from plant cells to yeast and human cells, it is still poorly characterized and understood. Such tRNA fragmentation has previously been thought to affect a small fraction of the tRNA pool and was thus presumed to not affect the role of tRNAs in translation. We report that in human cells, oxidative stress can rapidly generate tRFs derived from tyrosyl tRNAGUA—resulting in a significant depletion of the precursor tRNA molecule …
Chemical Biology, Biochemical And Structural Studies Of Mdn1, An Aaa Protein Required For Ribosome Biogenesis, Zhen Chen
Student Theses and Dissertations
Cellular proteins are synthesized by ribosomes, which are ~3 MDa macromolecular complexes comprised of four ribosomal RNAs and ~80 ribosomal proteins in yeast. The biogenesis of such complicated ribonucleoprotein complexes is a highly regulated, multistep process requiring a plethora of more than 200 unique assembly factors. Energy-harnessing enzymes, such as ATPases and GTPases, are needed to remodel the precursors of ribosomes at fast time scales. Mdn1 is an essential dynein-like AAA protein (ATPases Associated with various Activities) that releases specific assembly factors from the precursors of 60S subunit of ribosomes. However, Mdn1’s unusually large size (~5000 amino acids in a …
Multimodal Strategies Of Host-Seeking Mosquitoes, Molly Zhen Liu
Multimodal Strategies Of Host-Seeking Mosquitoes, Molly Zhen Liu
Student Theses and Dissertations
Mosquitoes use multiple sensory modalities, including olfaction, thermosensation, and vision, to hunt human hosts and obtain a blood-meal for egg production. Any individual sensory cue is an incomplete signal of a human host, and so a mosquito must integrate multimodal sensory information before committing to approaching and biting a person. Mosquito host-seeking behavior is thus a particularly fruitful model for studying multimodal integration because of its robustness, intricacy, and public health importance. Using tethered and free flight assays, we have teased apart responses to attractive visual and thermal cues in female Aedes aegypti, the yellow fever mosquito, uncovering their contributions …
Oxytocin, Dopamine, And The Neuromodulation Of Mating Behavior In C. Elegans, Meghan Aileen Lockard
Oxytocin, Dopamine, And The Neuromodulation Of Mating Behavior In C. Elegans, Meghan Aileen Lockard
Student Theses and Dissertations
No abstract provided.
Substrate Identification Of An Oncogenic Kinase: Elucidating The Pathogenesis Of A Rare Liver Cancer, Melissa Jarmel
Substrate Identification Of An Oncogenic Kinase: Elucidating The Pathogenesis Of A Rare Liver Cancer, Melissa Jarmel
Student Theses and Dissertations
Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer with limited treatment options. This cancer primarily affects adolescents and young adults. Our lab has identified a new fusion gene in this cancer called DNAJB1-PRKACA that results from a break and re-fusion in chromosome 19. This chimeric gene results in a fusion kinase that acts as the driver of this cancer. While we have shown that the kinase activity of the fusion protein is essential for transformation, it is not currently known whether the oncogenic kinase that results from this fusion event, DNAJB1- PRKACA, phosphorylates the same substrates as PRKACA, the …
From Face Perception To Individual Recognition: The Missing Link, Sofia Mariana Landi
From Face Perception To Individual Recognition: The Missing Link, Sofia Mariana Landi
Student Theses and Dissertations
Recognizing other individuals is a key social aspect of our everyday lives. To recognize a familiar individual, we must establish a link between sensory inputs and a representation of that individual held in memory. In primates, faces play a particularly important role on the sensory side of this process, which is reflected in an extensive network of face-selective areas along the inferior temporal lobe. However, where and how memory is re-activated during face perception remains unclear. Using functional magnetic resonance imaging (fMRI), we measured whole brain activity in macaques while they were watching pictures of other monkey faces that were …
Molecular Mechanisms Underlying Stress-Induced Glia Remodeling In The Nematode C. Elegans, In Hae Lee
Molecular Mechanisms Underlying Stress-Induced Glia Remodeling In The Nematode C. Elegans, In Hae Lee
Student Theses and Dissertations
Animals can adapt to long-term environmental changes by modifying their behavior, which can be accompanied by structural alterations of the nervous system. Such alterations are common in sensory organs, composed of sensory neurons and glia, which initially detect environmental stress. The molecular mechanisms driving cell shape remodeling following environmental stress and the effects of such remodeling on animal survival are not well understood. C. elegans is an excellent model in which to study neuronal and glial cell remodeling. Under normal growth conditions, the sensory receptive endings of the bilateral AWC sensory neurons, which respond to volatile odorants, are individually ensheathed …
Examining Mechanisms Regulating Microtubule Assembly And Function, Melissa Pamula
Examining Mechanisms Regulating Microtubule Assembly And Function, Melissa Pamula
Student Theses and Dissertations
Microtubules are cytoskeletal polymers assembled from α and β tubulin subunits that function in essentially all cellular activities. Microtubules can act as “tracks” for intracellular cargo transport, are required for cilia- and flagella-based motility, and establish cell morphology in specialized cells such as neurons. In dividing cells, a bipolar spindle assembles from microtubules and partitions genetic material into two daughter cells. Proper microtubule function in these diverse contexts depends on the assembly dynamics of microtubules and their organization into specialized arrays. Both intrinsic factors including the tubulin isotype composition of microtubules and extrinsic factors including microtubule-associated proteins (MAPs) can impact …
Elucidation Of The Functional Architecture Of The Early Pre-Ribosomal Processing Machinery In Yeast, Mirjam Hunziker
Elucidation Of The Functional Architecture Of The Early Pre-Ribosomal Processing Machinery In Yeast, Mirjam Hunziker
Student Theses and Dissertations
Ribosomes carry out one of the most fundamental functions of life - the translation of genetic information into functional proteins. The pivotal role of the ribosome in the cell is reflected in its immensely complicated and energy-consuming assembly pathway. The maturation of a eukaryotic ribosome involves more than 200 non-ribosomal factors and the activity of all three RNA polymerases. In yeast, ribosome biogenesis starts with the transcription of the 35S pre-ribosomal RNA in the nucleolus. This large RNA molecule contains three of the four ribosomal RNAs separated by several internal and external transcribed spacer regions. The 5’ external transcribed spacer …
Conformational Dynamics Of The Nuclear Pore Complex Studied With Coarse-Grained Modelling And Polarized Light Microscopy, Joan Pulupa
Student Theses and Dissertations
In my thesis work, I explored the organization and dynamics of the nuclear pore complex (NPC) through coarse-grained modelling and polarized-total internal reflection fluorescence (pol-TIRF) microscopy. The NPC is a large (~120 MDa in humans) macromolecular assembly that controls the flow of molecules into and out of the nucleus. The NPC is a key regulator of intracellular trafficking, nuclear organization, and gene expression. The study of this cellular gatekeeper is hampered by its size and complexity, as well as the difficulty of measuring protein dynamics in vivo. Although various models for how cargo translocates the NPC have been proposed, the …
Distinct Populations Of Layer 5b Pyramidal Neurons In The Primary Motor Cortex, Maria V. Moya
Distinct Populations Of Layer 5b Pyramidal Neurons In The Primary Motor Cortex, Maria V. Moya
Student Theses and Dissertations
The ability of motor cortex to plan, execute, and refine different movements depends on the coordinated activity of many neurons found across its laminar structure. Layer 5b (L5b), a deep cortical layer that drives output signals from the cortex, contains excitatory pyramidal neurons that innervate many subcortical areas of the brain. In the motor cortex, L5b is thicker and contains more pyramidal neurons than L5b of other cortical areas. Electrophysiological, anatomical, and RNA-Seq profiling of neurons in the motor cortex suggests there are diverse pyramidal neuron types within L5b. However, the precise identities of these distinct populations and their defining …
Functional Organization Of Molecular Memories In The Crispr-Cas Immune System, Jon Mcginn
Functional Organization Of Molecular Memories In The Crispr-Cas Immune System, Jon Mcginn
Student Theses and Dissertations
CRISPR-Cas systems endow bacteria and archaea with adaptive immunity against foreign genetic threats, like phages and plasmids. These immune systems are comprised of CRISPR-associated (Cas) protein effectors and DNA-based storage of immunological memories in the CRISPR array. The CRISPR array is a series of direct repeats intercalated by variable spacer sequences (~30bp) of foreign origin. Upon infection, spacers are excised from the foreign genome and integrated into the array. The array is then transcribed and parsed into individual CRISPR RNAs, each containing a single spacer sequence, which are used by Cas nucleases to identify foreign nucleic acids for destruction. Thus, …
Who Said That? Towards A Machine-Prediction-Based Approach To Tursiops Truncatus Whistle Localization And Attribution In A Reverberant Dolphinarium, Sean Fisher Woodward
Who Said That? Towards A Machine-Prediction-Based Approach To Tursiops Truncatus Whistle Localization And Attribution In A Reverberant Dolphinarium, Sean Fisher Woodward
Student Theses and Dissertations
Dolphin communication research is an active period of growth. Many researchers expect to find significant communicative capacity in dolphins given their known sociality and large and complex brains. Moreover, given dolphins’ known acoustic sensitivity, serving their well-studied echolocation ability, some researchers have speculated that dolphin communication is mediated in large part by a sophisticated “vocal” language. However, evidence supporting this belief is scarce. Among most dolphin species, a particular tonal class of call, termed the whistle, has been identified as socially important. In particular, for the common bottlenose dolphin, Tursiops truncatus – arguably the focal species of most dolphin cognitive …
The Skin Remembers: Epigenetic Memories Of Inflammation Past, Samantha B. Larsen
The Skin Remembers: Epigenetic Memories Of Inflammation Past, Samantha B. Larsen
Student Theses and Dissertations
As one of the body’s largest environmental interfaces, the skin is routinely exposed to a myriad of inflammatory stimuli. It functions as a barrier acting as the first line of defense against pathogens, while simultaneously protecting the organism from dehydration. Maintaining an intact barrier is therefore paramount to organismal survival, and the foremost torchbearers of this task are skin epithelial stem cells (EpSCs). EpSCs reside in the basal layer of the skin, survive long-term, and are capable of both self-renewing and differentiating into multiple skin lineages. To efficaciously maintain the barrier, EpSCs must be able to sense and respond to …
Regulation Of Protein Degradation By Adp-Ribosylation, Yetis Gultekin
Regulation Of Protein Degradation By Adp-Ribosylation, Yetis Gultekin
Student Theses and Dissertations
Protein quality control is essential for cellular homeostasis. The Ubiquitin-Proteasome System (UPS) is responsible for the regulated breakdown of intracellular proteins. All proteins are not degraded at the same rate in the cell. For instance, global protein turnover rates in mammals change with an average time between 1-2 days. On the other hand, a handful of proteins such as myelin exhibits limited turnover for months or even years. The UPS recycles most of the short-lived proteins in a time range from minutes to days depending on their localization and post-translational modifications. The post-translational modification, poly-ADPribosylation has an estimated half-life of …