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Articles 31 - 60 of 699
Full-Text Articles in Life Sciences
Restriction-Modification And Crispr-Cas Systems: Cooperation Between Innate And Adaptive Immunity In Prokaryotes, Pascal Maguin
Restriction-Modification And Crispr-Cas Systems: Cooperation Between Innate And Adaptive Immunity In Prokaryotes, Pascal Maguin
Student Theses and Dissertations
Bacteria have evolved numerous mechanisms to resist the constant assault of viruses (called bacteriophages, or simply phages) that can infect and kill them. Restriction-modification (RM) systems represent one such strategy. Generally, these systems provide defense by coordinating the activities of two distinct enzymes: a restriction endonuclease and a methyltransferase. Both enzymes recognize the same short DNA sequences. The methyltransferase modifies these target sites in the host chromosome, which prevents the restriction endonuclease from cleaving the host’s own DNA. In contrast, foreign phage DNA is usually not methylated at these sequences. Consequently, upon injection into the host, the viral DNA is …
Sensory And Neuromodulatory Entrainment Of Foraging States In C. Elegans, Elias Scheer
Sensory And Neuromodulatory Entrainment Of Foraging States In C. Elegans, Elias Scheer
Student Theses and Dissertations
Foraging animals dynamically adjust their behavioral patterns over time to optimize feeding in their environment. In the nematode Caenorhabditis. elegans, foraging animals alternate between states of locomotory arousal. I observed that animals in low activity states remain nearby food patches, whereas highly aroused animals often exit patches to explore the external environment. Using different methods of behavioral state classification reveals different aspects of foraging behavior: previously described high arousal roaming and low arousal dwelling states reflect long-term changes in locomotory patterns, whereas an Autoregressive Hidden Markov model that classifies behavior on shorter time scales effectively segments food leaving behaviors. Adaptive …
Tumor Suppression By A Trna Synthetase, Maria Passarelli
Tumor Suppression By A Trna Synthetase, Maria Passarelli
Student Theses and Dissertations
Despite substantial progress in treatment, breast cancer remains a leading cause of cancer mortality among women. During malignant transformation, healthy mammary cells must bypass tumor suppressive checkpoints and activate pro-growth pathways. Enhanced protein translation is one such hallmark of tumor transformation and cancer progression; many oncogenes promote translation by driving synthesis and activity of translational machinery. In the first part of this thesis, we report the surprising finding that leucyl-tRNA synthetase (LARS), a tRNA synthetase responsible for ligating leucine to corresponding leucyl-tRNAs, becomes strongly repressed during mammary cell transformation and in breast cancer. Monoallelic genetic inactivation of LARS in mouse …
The Effect Of Early Dietary Intervention On Alzheimer's Disease-Related Pathology And Cognitive Function In Mice, Anna Amelianchik
The Effect Of Early Dietary Intervention On Alzheimer's Disease-Related Pathology And Cognitive Function In Mice, Anna Amelianchik
Student Theses and Dissertations
Alzheimer’s disease (AD) is a fatal cognitive disorder with proteinaceous brain deposits, neuroinflammation, cerebrovascular dysfunction, and extensive neuronal loss. AD is a multifactorial disease, and lifestyle factors, including diet, are likely associated with the development of AD pathology. Since obesity and diabetes are recognized as risk factors for AD, it might be predicted that a high fat diet (HFD) would worsen AD pathology. However, modeling HFD-induced obesity in animal models of AD has yielded inconclusive results. Some studies report a deleterious effect of HFD on Aβ accumulation, neuroinflammation, and cognitive function, while others report that HFD worsens memory without affecting …
Multi-Modal Regualtion Of Actin Networks, Lin Mei
Multi-Modal Regualtion Of Actin Networks, Lin Mei
Student Theses and Dissertations
Eukaryotic cells employ the actin cytoskeleton to maintain cell shape, support motility, and sense and respond to external mechanical stimuli. An intricate network of actin filaments constitutes the foundation of tissue architecture by forming key cellular structures including the muscle fiber, the filopodium, the lamellipodium, and the cell cortex. Cellular and tissue level studies have shown that more than 150 actin-binding proteins regulate almost every single aspect of actin physiology, such as actin polymerization, actin severing, and actin crosslinking, but at the molecular level, the structural mechanisms by which different actin binding proteins bind, assemble, and regulate different actin networks …
Characterization Of A Novel Sensing Mechanism Governing Antigenic Variation In P. Falciparum, Victoria M. Schneider
Characterization Of A Novel Sensing Mechanism Governing Antigenic Variation In P. Falciparum, Victoria M. Schneider
Student Theses and Dissertations
Plasmodium falciparum expresses a multi-copy gene family called var in the intraerythroyctic stages of its life cycle in a mutually exclusive manner. var genes encode the chief antigenic and virulence determinant of P. falciparum, PfEMP1, and switching between active genes results in antigenic variation, allowing the parasite to evade the human immune system and cause chronic infections. The molecular mechanisms that control activation and silencing of individual var genes, as well as coordination of the switching process, presently remain incompletely defined. P. falciparum contains only ~60 var gene family members in its genome. Consequently, the question remains as to how …
Ultra-Fast And Multi-Dimensional Face Processing In A New Face Area, Zetian Yang
Ultra-Fast And Multi-Dimensional Face Processing In A New Face Area, Zetian Yang
Student Theses and Dissertations
Faces contain a plethora of information crucial for social interactions. Facial information could be transmitted either through facial shape or motion. The last two decades have established that a network of face-selective areas in the temporal lobe of macaque monkeys supports the visual processing of faces. Most of these studies focused on the processing of static facial shape. They found that each area within the face network contains a large fraction of face-selective cells. And each area encodes facial identity and head orientation differently. A recent brain imaging study discovered a new face area outside of this classic network, the …
Structural Studies Of The Nucleolar Stages Of Ribosome Biogenesis In Yeast, Linamarie Miller
Structural Studies Of The Nucleolar Stages Of Ribosome Biogenesis In Yeast, Linamarie Miller
Student Theses and Dissertations
The ribosome is the RNA-protein machine responsible for the essential task of translating mRNA into proteins. Ribosomes are heterodimers made up of a small subunit (SSU, 40S) and a large subunit (LSU, 60S). At the interface of these subunits, the mRNA is decoded by the small subunit and peptide bond formation is catalyzed by the rRNA of the large subunit. The cell therefore requires the timely and accurate assembly of functional ribosomal subunits, a complex process termed ribosome biogenesis. In addition to the ribosomal RNAs and ribosomal proteins that make up the mature subunits, eukaryotic cells require over 200 trans-acting …
53bp1/Shieldin Counteract Dsb Resection Through Fill-In Synthesis, Zachary Kenneth Mirman
53bp1/Shieldin Counteract Dsb Resection Through Fill-In Synthesis, Zachary Kenneth Mirman
Student Theses and Dissertations
53BP1 is a DNA damage response (DDR) factor that gained notoriety because it determines the efficacy of PARP1 inhibitors (PARPi) in BRCA1-deficient cancers. Additionally, 53BP1 promotes end-to-end fusions of telomeres lacking end protection from the shelterin component TRF2, and facilitates end-joining at programmed breaks generated during class switch recombination in the immune system. The role of 53BP1 in double strand break (DSB) repair outside of these three well-studied contexts is less clear, though it has been proposed that 53BP1 acts as a master regulator of so-called “DSB repair pathway choice,” promoting classical non-homologous end-joining (cNHEJ) at the expense of homology-directed …
Ras Drives Malignancy Through Stem Cell Crosstalk With The Microenvironment, Shaopeng Yuan
Ras Drives Malignancy Through Stem Cell Crosstalk With The Microenvironment, Shaopeng Yuan
Student Theses and Dissertations
Squamous cell carcinomas (SCCs) are triggered by marked elevation of RAS/MAPK signaling and progression from benign papilloma to invasive malignancy. A subset of tumor-initiating basal progenitors, the cancer stem cells, obtain increased resistance to chemo and immunotherapy along this path. However, the distribution and changes in cancer stem cells during progression from a benign state to an invasive SCC remain elusive. Here we show that following HRASG12V activation, cancer stem cells rewire their gene expression program and trigger self-propelling, aberrant signaling crosstalk with their tissue microenvironment that drives their malignant progression. Surprisingly, the non-genetic, dynamic cascade of crosstalk involves pathways …
Uncovering Regulators Of Whole-Body Metabolism By Chemoproteomic Profiling Of The Adipocyte Secretome, Chan Hee J Choi
Uncovering Regulators Of Whole-Body Metabolism By Chemoproteomic Profiling Of The Adipocyte Secretome, Chan Hee J Choi
Student Theses and Dissertations
A major threat to human health, obesity is associated with increased risk of cardiometabolic complications such as cardiovascular disease, type 2 diabetes, hypertension, and many types of cancers. Whereas white adipocytes efficiently store energy in the form of triglycerides, thermogenic brown and beige adipocytes can dissipate energy into heat. Adipose tissue is now considered an important endocrine organ, and increasing evidence suggests that divergent metabolic effects of different types of adipocytes are in part mediated by their secretory function. In addition, dysregulation of adipose tissue’s secretory function in the setting of chronic positive energy balance plays a central role in …
Structure And Mechanism Of Pcat1, A Polypeptide Processing And Secretion Transporter, Virapat Kieuvongngam
Structure And Mechanism Of Pcat1, A Polypeptide Processing And Secretion Transporter, Virapat Kieuvongngam
Student Theses and Dissertations
ATP-binding cassette (ABC) transporters utilize the energy from ATP to transport substrates across biological membranes. Various ABC transporters perform diverse biological functions across all forms of life ranging from importing essential nutrients to exporting toxic drugs (Ford and Beis 2019; ter Beek, Guskov, and Slotboom 2014). Bacterial cells utilize a class of ABC transporters for exporting proteins or peptides. Unlike the Sec translocon machinery, the ABC peptide exporters are dedicated to specific peptides (Fath and Kolter 1993). These peptides function as quorum sensing peptides, biofilms, or antimicrobial peptides. Among these ABC peptide exporters are Peptidase Containing ABC Transporters (PCATs) that …
Peptidergic Signaling Controls The Dynamics Of Sickness Behavior In Caenorhabditis Elegans, Javier Marquina-Solis
Peptidergic Signaling Controls The Dynamics Of Sickness Behavior In Caenorhabditis Elegans, Javier Marquina-Solis
Student Theses and Dissertations
Disease is accompanied by modifications to host behavior that promote recovery and survival. The neural and molecular mechanisms that rule the switch to a sickness behavioral state are an active area of research. One established model for sickness behavior is the interaction between Caenorhabditis elegans and the pathogenic bacteria Pseudomonas aeruginosa PA14. After a few hours of exposure to and infection by PA14, C. elegans develops a sickness-like behavior termed pathogen avoidance. Here I identify neuronal signals generated during the infection and associate them with antagonistic circuits that shape the host behavior. Using an unbiased cell-directed neuropeptide screen, I show …
Building An Allocentric Traveling-Direction Signal Via Vector Computation, Cheng Lyu
Building An Allocentric Traveling-Direction Signal Via Vector Computation, Cheng Lyu
Student Theses and Dissertations
Many behavioral tasks require the manipulation of mathematical vectors, but, outside of computational models, it is not known how brains perform vector operations. Here we show how the Drosophila central complex, a region implicated in goal-directed navigation, performs vector arithmetic. First, we describe a neural signal in the fan-shaped body that explicitly tracks a fly's allocentric traveling angle, that is, the traveling angle in reference to external cues. Past work has identified neurons in Drosophila and mammals that track an animal's heading angle referenced to external cues (e.g., head-direction cells), but this new signal illuminates how the sense of space …
Nonlinear Representation Of Auditory Stimuli Across The Auditory Cortex, Frank Tejera Leon
Nonlinear Representation Of Auditory Stimuli Across The Auditory Cortex, Frank Tejera Leon
Student Theses and Dissertations
The neural evoke activity to pure tones in primary auditory cortex has been systematically studied for many years, as has the spatial organization of these responses. Unlike pure tones, natural sounds possess complex spectro-temporal structures across frequencies. How simple tuning properties scale across ensembles of neurons to represent more complex sensory environments is still a question of active investigation and debate. To better understand the coding principles used to represent complex auditory sounds, we performed 2-photon calcium imaging of neural activity of the entire auditory cortex in awake mice, while playing sounds composed of single or multiple frequencies. While we …
A Developmental Pathway For Epithelial-To-Motoneuron Transformation In C. Elegans, Alina Rashid
A Developmental Pathway For Epithelial-To-Motoneuron Transformation In C. Elegans, Alina Rashid
Student Theses and Dissertations
During animal development, neurons and neuron-like cells are generated from progenitor cells that often line tubes. For example, in the developing spinal cord, basal processes of radial glial stem cells line the fluid-filled spinal canal. Notch/Delta signaling is implicated in the differentiation of these cells into motoneurons through control of their proliferative state. Down-regulation of the Notch-dependent Hes1 and Hes5 transcriptional inhibitors in differentiating cells induces expression of the proneural bHLH transcription factors Olig2 and Ngn2, leading to adherens junction loss, delamination from the epithelium, cell migration, and neuronal maturation. A similar sequence of events characterizes formation of pancreatic insulin-secreting …
Human Antibody Response To Flaviviruses And Sars-Coronavirus-2, Marianna Elizabeth Agudelo
Human Antibody Response To Flaviviruses And Sars-Coronavirus-2, Marianna Elizabeth Agudelo
Student Theses and Dissertations
The last decade has seen a number of viral epidemics and global pandemic. Increased global connectivity makes the likelihood of future mass outbreaks ever greater. Understanding the adaptive immune response to these pathogens will expand basic understanding of viral immunity mechanisms and can help inform vaccine and therapeutic development. This thesis describes the characterization of the human antibody response to several important viral pathogens, all of which are either emerging pathogens posing significant public health burdens or are already responsible for epidemic outbreaks. These include tick-borne encephalitis virus (TBEV), Powassan virus (POWV), Zika virus (ZIKV) and severe acute respiratory syndrome …
Linker Histone Medicated Regulation Of Mitotic Chromosome Compaction And Individualization, Pavan Choppakatla
Linker Histone Medicated Regulation Of Mitotic Chromosome Compaction And Individualization, Pavan Choppakatla
Student Theses and Dissertations
Mitotic chromosomes are scaled to the cell size to ensure effective chromosome segregation. Recent studies have shown how condensins and DNA topoisomerase II organize the mitotic chromosome. However, the regulation of these factors in maintaining proper chromosome size in different cell types remains a mystery. Here, I investigated the role of the linker histone variant H1.8 in regulating mitotic chromosome structure. I showed that H1.8 suppresses binding of condensins and topo II to mitotic chromatin in Xenopus egg extracts. Using an in vitro reconstitution system, I showed that H1.8 inhibits binding of purified condensins and topo II to nucleosome arrays. …
Unraveling The Interaction Between Beige Adipocytes And The Sympathetic Nervous System, Jingyi Chi
Unraveling The Interaction Between Beige Adipocytes And The Sympathetic Nervous System, Jingyi Chi
Student Theses and Dissertations
Obesity affects more than one in three adults in the United States and is a significant risk factor for a constellation of chronic diseases. The crucial role of adipose tissue in energy balance has driven great interest in investigating this tissue as a target for treatment of obesity and its sequelae. While white adipocytes store excess energy, thermogenic brown and beige adipocytes convert lipids and glucose into heat, thereby increasing energy expenditure. Unlike classical brown adipocytes which are thermogenic under basal conditions, inducible brown adipocytes, commonly known as beige adipocytes, reside in white adipose depots and need to be activated …
Metabolic Coordination Of Stem Cell Fate Controls Tumor Initiation And Tissue Repair, Sanjeethan C. Baksh
Metabolic Coordination Of Stem Cell Fate Controls Tumor Initiation And Tissue Repair, Sanjeethan C. Baksh
Student Theses and Dissertations
Tissue stem cells balance fate decisions of self-renewal and differentiation to maintain homeostasis over the lifetime of an organism, as well as to repair tissues upon injury and wounding. Disrupting the balance between self-renewal and differentiation results in pathology: excessive self-renewal at the expense of differentiation is associated with tumor initiation, whereas failure to properly self-renew leads to stem cell exhaustion and aging. Stem cell fate is under tight regulation by the surrounding microenvironment, or niche, which includes neighboring cell types, signaling molecules, extracellular matrix, and nutrients. While the role of stromal cells and the signals they produce has been …
Not Black And White: Bmp Signaling Drives Melanocyte Differentiation Down Stream Of Stem Cell Activation, Nicole Rai Infarinato
Not Black And White: Bmp Signaling Drives Melanocyte Differentiation Down Stream Of Stem Cell Activation, Nicole Rai Infarinato
Student Theses and Dissertations
Tissue stem cells (SCs) maintain, regenerate, and repair the body over the course of an organism’s lifetime. To preserve their long-term function, SCs must exert precise control over their cell state dynamics as they move from quiescence to activation and commit to full differentiation. My graduate research has been centered on investigating the molecular mechanisms that fuel these transitions in melanocyte stem cells (McSCs), a unique neural crest-derived SC population located in the hair follicle (HF). Through periodic bouts synchronous with HF cycling, quiescent McSCs become activated to proliferate, giving rise to committed proliferative progeny (McCP) that differentiate into mature …
The Taste Of Blood, Veronica Jove
The Taste Of Blood, Veronica Jove
Student Theses and Dissertations
Human blood and floral nectar are both appetizing meals to a hungry female mosquito, yet each meal fulfills a distinct nutritional requirement. While protein obtained from blood is required for females to develop eggs and successfully reproduce, carbohydrates supplied from plant nectar are sufficient for energy metabolism in both females and males. To procure essential nutrients from these distinct food sources, females employ two mutually exclusive feeding programs with unique sensory appendages, meal sizes, digestive tract targets, and metabolic fates. When a female is ready to reproduce, she must selectively seek the taste of blood and ignore the sweet taste …
Mechanisms For The Evolution Of Superorganismality In Ants, Vikram Chandra
Mechanisms For The Evolution Of Superorganismality In Ants, Vikram Chandra
Student Theses and Dissertations
Ant colonies appear to behave as superorganisms; they exhibit very high levels of within-colony cooperation, and very low levels of within-colony conflict. The evolution of such superorganismality has occurred multiple times across the animal phylogeny, and indeed, origins of multicellularity represent the same evolutionary process. Understanding the origin and elaboration of superorganismality is a major focus of research in evolutionary biology. Although much is known about the ultimate factors that permit the evolution and persistence of superorganisms, we know relatively little about how they evolve. One limiting factor to the study of superorganismality is the difficulty of conducting manipulative experiments …
The Role Of Nutrient Availability In Therapeutic Response Of Leukemia, Rohiverth Guarecuco Jr
The Role Of Nutrient Availability In Therapeutic Response Of Leukemia, Rohiverth Guarecuco Jr
Student Theses and Dissertations
Tumor environment influences the response to anti-cancer therapy, but which extracellular nutrients impact drug sensitivity is largely unknown. In this work, we used functional genomics to identify metabolic modifiers of the response to L-asparaginase (ASNase), a therapy that depletes plasma asparagine and targets leukemic cells with insufficient asparagine synthesis. Our approach revealed thiamine pyrophosphate kinase 1 (TPK1), which converts vitamin B1 (thiamine) into the cofactor thiamine pyrophosphate (TPP), as a metabolic dependency under ASNase treatment. In glutamine-anaplerotic leukemia cells, we found that TPP availability enables asparagine synthesis from extracellular glutamine. Mechanistically, TPP is critical for the activity of alpha-ketoglutarate dehydrogenase …
Tension Propagation Along Tip-Link Cadherins: Regulation And Implications For The Auditory System, Daniel M. Firester
Tension Propagation Along Tip-Link Cadherins: Regulation And Implications For The Auditory System, Daniel M. Firester
Student Theses and Dissertations
Hair bundles detect sound by shearing in response to vibrations spanning orders of magnitude in intensity and frequency. Their responsiveness stems from mechanosensitive ion channels that sit atop the stereocilia and are gated by tension in tip links. Experimental evidence and theoretical arguments implicate a soft compliant element, with a stiffness of 1-4 mN/m, as necessary for mechanotransduction. Although the identity of this element remains an open question, direct measurements of a component of the tip link have highlighted entropic elasticity as one relevant characteristic. A tip link comprises a heterotetremer of protocadherin-15 and cadherin-23, arranged in a loose helical …
Non-Canonical Axonal Insulin Receptor Signaling Drives Aversive Olfactory Learning, Du Cheng
Non-Canonical Axonal Insulin Receptor Signaling Drives Aversive Olfactory Learning, Du Cheng
Student Theses and Dissertations
Animals rely on their flexible nervous systems to learn to navigate the changing environment around them. One important function of the nervous system is to form associative memories. A simple model of associative learning is provided by nematode C. elegans, which can form memories of different types of odor stimuli through its simple yet sophisticated nervous system. C. elegans uses its sensory neurons to detect and navigate towards the odors of its food source - edible bacteria. Thus, it is crucial for worms to form memories between odors and availably of food. The volatile chemical butanone is a common product …
Brochemical Studies Of Peptidoglycan Hydrolases From Commensal And Pathogenic Bacteria, Juliel Espinosa
Brochemical Studies Of Peptidoglycan Hydrolases From Commensal And Pathogenic Bacteria, Juliel Espinosa
Student Theses and Dissertations
The intestinal microbiota consists of diverse bacterial species and their effectors that play key roles in regulating human health. Interestingly, cell wall, or peptidoglycan, fragments from commensal and pathogenic bacteria can activate host immunity. The mechanism(s) by which immunologically active peptidoglycan fragments are generated, however, are not well-understood. In this regard, peptidoglycan hydrolases are ubiquitous in bacteria and possess diverse activities to remodel the cell wall during cell growth and division. These peptidoglycan hydrolases can also generate cell wall fragments in this process that are shed or recycled and available for triggering host immunity. In this thesis, we describe methodologies …
Accessory Nucleases Provide Robust Antiparasite Immunity For Type Iii Crispr-Cas Systems, Jakob Træland Rostøl
Accessory Nucleases Provide Robust Antiparasite Immunity For Type Iii Crispr-Cas Systems, Jakob Træland Rostøl
Student Theses and Dissertations
To protect against parasites like bacteriophages and plasmids, bacteria employ diverse and sophisticated defence systems. Clustered, regularly interspaced short palindromic repeats (CRISPR)-Cas systems are adaptive immune systems that can integrate short “spacers” from a parasite into its CRISPR locus as a form of immunological memory. Upon reinfection, short RNAs transcribed from the CRISPR locus can guide Cas proteins to the viral genome through complementary base pairing. Cas nucleases then destroy the invader’s genome. To date, six major types and multiple subtypes of CRISPR systems exist, each with their own signature genes and mechanisms of action. Type III CRISPR systems are …
The Role Of Dna Methylation In Defining The Vocal Learning Transcriptome Of The Zebra Finch, Caitlin Sun Gilbert
The Role Of Dna Methylation In Defining The Vocal Learning Transcriptome Of The Zebra Finch, Caitlin Sun Gilbert
Student Theses and Dissertations
Vocal learning is a rare, complex behavior which is a critical component of human spoken language acquisition. It is convergent across several independent lineages of birds and mammals, including songbirds and humans. The development of speech and song production in humans and songbirds is strikingly similar, though the molecular mechanisms underlying these similarities are not yet understood. Our lab has previously found convergently differentially expressed genes in the vocal learning circuitry of humans and song-learning birds relative to adjacent non-vocal motor circuits. Most notably, the RA song nucleus in the songbird is molecularly convergent with the human laryngeal motor cortex. …
A Proteomic Approach To Elucidating The Function Of Picornavirus 2a Protease, Artem Serganov
A Proteomic Approach To Elucidating The Function Of Picornavirus 2a Protease, Artem Serganov
Student Theses and Dissertations
Human-infecting viruses have evolved diverse strategies to enter cells and hijack the host machinery to promote their self-replication. Viruses deploy their proteins to subvert a number of host functions, such as the cell cycle, cellular metabolism, protein synthesis, nuclear and RNA transport across the nuclear pore complex, apoptosis, and innate immune responses. Picornaviruses are the most dominant human disease-causing viruses and present an excellent clinical target for research studies into their molecular mechanisms. Picornaviruses have an RNA genome that is translated as a single polyprotein, which is processed into individual components by two proteases, termed 2A and 3C. In addition …