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Articles 7921 - 7950 of 9784

Full-Text Articles in Genetics and Genomics

Comparative Transcriptional Profiling Identifies Takeout As A Gene That Regulates Life Span, Johannes Bauer, Michael Antosh, Chengyi Chang, Christoph Schorl, Santharam Kolli, Nicola Neretti, Stephen L. Helfand May 2010

Comparative Transcriptional Profiling Identifies Takeout As A Gene That Regulates Life Span, Johannes Bauer, Michael Antosh, Chengyi Chang, Christoph Schorl, Santharam Kolli, Nicola Neretti, Stephen L. Helfand

Biosciences Research

A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular …


A Brain-Specific Cytochrome P450 Responsible For The Majority Of Deltamethrin Resistance In The Qtc279 Strain Of Tribolium Castaneum, Fang Zhu, R. Parthasarathy, Hua Bai, Katharina Woithe, Martin Kaussmann, Ralf Nauen, Douglas A. Harrison, Subba R. Palli May 2010

A Brain-Specific Cytochrome P450 Responsible For The Majority Of Deltamethrin Resistance In The Qtc279 Strain Of Tribolium Castaneum, Fang Zhu, R. Parthasarathy, Hua Bai, Katharina Woithe, Martin Kaussmann, Ralf Nauen, Douglas A. Harrison, Subba R. Palli

Entomology Faculty Publications

Cytochrome P450-mediated detoxification is one of the most important mechanisms involved in insecticide resistance. However, the molecular basis of this mechanism and the physiological functions of P450s associated with insecticide resistance remain largely unknown. Here, we exploited the functional genomics and reverse genetic approaches to identify and characterize a P450 gene responsible for the majority of deltamethrin resistance observed in the QTC279 strain of Tribolium castaneum. We used recently completed whole-genome sequence of T. castaneum to prepare custom microarrays and identified a P450 gene, CYP6BQ9, which showed more than a 200-fold higher expression in the deltamethrin-resistant QTC279 strain when compared …


Assessing The Phylogenetic Utility Of Dna Barcoding Using The New Zealand Cicada Genus Kikihia, Megan Ribak May 2010

Assessing The Phylogenetic Utility Of Dna Barcoding Using The New Zealand Cicada Genus Kikihia, Megan Ribak

Honors Scholar Theses

DNA Barcoding (Hebert et al. 2003) has the potential to revolutionize the process of identifying and cataloguing biodiversity; however, significant controversy surrounds some of the proposed applications. In the seven years since DNA barcoding was introduced, the Web of Science records more than 600 studies that have weighed the pros and cons of this procedure. Unfortunately, the scientific community has been unable to come to any consensus on what threshold to use to differentiate species or even whether the barcoding region provides enough information to serve as an accurate species identification tool. The purpose of my thesis is to analyze …


A Family-Based Association Study Of Conduct Disorder., Xueqiu Jian May 2010

A Family-Based Association Study Of Conduct Disorder., Xueqiu Jian

Electronic Theses and Dissertations

Conduct disorder (CD) is a psychiatric syndrome in childhood and adolescence that is one of the most common childhood disorders with continuously increasing prevalence but uncertain pathogenesis. We performed a genome-wide, family-based association study of CD using P2BAT/FBAT software. The data is gathered from Collaborative Study on the Genetics of Alcoholism (COGA) and International Multi-Center ADHD Genetics Project (IMAGE).

Using COGA data, we identified 20 markers which showed suggestive associations (p<10-3) with CD. Nine of them are located in known genes. Two genes, ADAM10 and CAMK2A, which had been reported associated with Alzheimer's disease (AD), bipolar disorder, …


Error Correcting Codes And The Human Genome., Suzanne Mclean Lyle May 2010

Error Correcting Codes And The Human Genome., Suzanne Mclean Lyle

Electronic Theses and Dissertations

In this work, we study error correcting codes and generalize the concepts with a view toward a novel application in the study of DNA sequences. The author investigates the possibility that an error correcting linear code could be included in the human genome through application and research. The author finds that while it is an accepted hypothesis that it is reasonable that some kind of error correcting code is used in DNA, no one has actually been able to identify one. The author uses the application to illustrate how the subject of coding theory can provide a teaching enrichment activity …


Natural Competence In Thermoanaerobacter And Thermoanaerobacterium Species, A Joe Shaw, David A. Hogsett, Lee R. Lynd May 2010

Natural Competence In Thermoanaerobacter And Thermoanaerobacterium Species, A Joe Shaw, David A. Hogsett, Lee R. Lynd

Dartmouth Scholarship

Low-G+C thermophilic obligate anaerobes in the class Clostridia are considered among the bacteria most resistant to genetic engineering due to the difficulty of introducing foreign DNA, thus limiting the ability to study and exploit their native hydrolytic and fermentative capabilities. Here, we report evidence of natural genetic competence in 13 Thermoanaerobacter and Thermoanaerobacterium strains previously believed to be difficult to transform or genetically recalcitrant.

In Thermoanaerobacterium saccharolyticum JW/SL-YS485, natural competence- mediated DNA incorporation occurs during the exponential growth phase with both replicating plasmid and homologous recombination-based integration, and circular or linear DNA. In T. saccharolyticum, disruptions of genes similar to …


Development Of Representative Species-Level Molecular Markers And Morphological Character Analysis Of Leucothoid Amphipods (Crustacea: Amphipoda), Kristine Nicolle White May 2010

Development Of Representative Species-Level Molecular Markers And Morphological Character Analysis Of Leucothoid Amphipods (Crustacea: Amphipoda), Kristine Nicolle White

Dissertations

Leucothoid amphipods were investigated using morphology and molecular rDNA gene sequence fragments. The morphological diagnostic characters for traditional taxonomy have been clarified, a molecular marker for representative species has been developed, and one of the current anamorph-leucomorph connections has been confirmed with molecular sequence data. Ultimately this study has combined traditional morphological and modern molecular methods to clarify the taxonomy and to propose a preliminary phylogeny of the Leucothoidae. Analysis of 18S rDNA gene fragments from 13 species in two genera supported the current morphological species designations and the separation of the family into two clades. Combined analysis of 18S …


Molecular Analysis Of Trypanosoma Cruzi Isolates Obtained From Raccoons (Procyon Lotor) In Warren And Barren Counties Of Kentucky, Lipeng Bi May 2010

Molecular Analysis Of Trypanosoma Cruzi Isolates Obtained From Raccoons (Procyon Lotor) In Warren And Barren Counties Of Kentucky, Lipeng Bi

Masters Theses & Specialist Projects

Trypanosoma cruzi, the etiologic agent of Chagas disease, infects a variety of wild mammals in the southern United States, but it has only recently been isolated from raccoons trapped in the state of Kentucky. The purpose of the present study was to use a molecular genotyping approach, followed by DNA sequencing to determine the genotypes (type I, or types IIa-IIe) of 15 of the Kentucky isolates. DNA samples were prepared from 15 T. cruzi- isolates using a Qiagen mini kit, and PCR amplification was performed using published primers for the 24S α rDNA sequence (D71 and D72), the …


Xenobiotic Metabolism Genes And Clubfoot, Amy M. Sommer May 2010

Xenobiotic Metabolism Genes And Clubfoot, Amy M. Sommer

Dissertations and Theses (Open Access)

Idiopathic or isolated clubfoot is a common orthopedic birth defect that affects approximately 135,000 children worldwide. It is characterized by equinus, varus and adductus deformities of the ankle and foot. Correction of clubfoot involves months of serial manipulations, castings and bracing, with surgical correction needed in forty percent of cases. Multifactorial etiology has been suggested in numerous studies with both environmental and genetic factors playing an etiologic role. Maternal smoking during pregnancy is the only common environmental factor that has consistently been shown to increase the risk for clubfoot. Moreover, a positive family history of clubfoot and maternal smoking increases …


Validation Of The Activation Of Aurora B Kinase By Caenorhabditis Elegans To Usled-Like Kinase And The Identification Of Cyclin B3 As A Phospho-Specific Tlk-1 Interactor, Gary Michael Deyter May 2010

Validation Of The Activation Of Aurora B Kinase By Caenorhabditis Elegans To Usled-Like Kinase And The Identification Of Cyclin B3 As A Phospho-Specific Tlk-1 Interactor, Gary Michael Deyter

Dissertations and Theses (Open Access)

A hallmark of tumorigenesis and certain birth defect syndromes is the loss of ploidy that can result from incorrect chromosome segregation. Chromosomes that are not partitioned properly during mitosis are often fragmented, changing the genetic makeup of daughter cells. Inheriting extrachromosomal fragments that contain cell survival genes or losing chromosomal loci that encode tumor suppressors can promote tumor development. Thus, it is essential to elucidate molecular mechanisms required for correct chromosome segregation. Chromosomes are connected to mitotic spindle microtubules by way of a proteinacous, chromosome-bound organelle called the kinetochore. Two decades of research have confirmed that the conserved Aurora B/AIR-2 …


A Molecular Basis For Craniofacial Laterality In Fishes, Karen Adams May 2010

A Molecular Basis For Craniofacial Laterality In Fishes, Karen Adams

Renée Crown University Honors Thesis Projects - All

Laterality, the preference for development on one side of the body, is essential to the vertebrate body plan. While the vertebrate skeleton usually develops symmetrically, the processes underlying craniofacial laterality are not well understood. Using zebrafish and cichlids as model organisms, this study focuses on the molecular basis of symmetric craniofacial development. Fgf8, Retinoic Acid, and wnt11 were examined to analyze their involvement in regulating craniofacial laterality. Fgf8 is known to play a role in proper jaw development. Because fgf8 and Retinoic Acid interact to achieve laterality of the somites during somitogenesis, the role of Retinoic Acid in regulating …


Plastic And Genetic Determination Of Population, Community, And Ecosystem Properties In Freshwater Environments, Leigh C. Latta Iv May 2010

Plastic And Genetic Determination Of Population, Community, And Ecosystem Properties In Freshwater Environments, Leigh C. Latta Iv

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The hierarchy of biological organization, from molecules to ecosystems, describes the relationships among various biological systems. Of particular interest is assessing how the factors that primarily determine the nature of one hierarchical level also have transcendent qualities that affect the ecology and evolution of higher hierarchical levels. The goal of this dissertation was to use a bottom-up approach to examine the transcendent effects of two factors that strongly determine the nature of their associated level of biological organization. The first, phenotypic plasticity, is a primary factor that determines the phenotype of an individual. The second factor, genetic diversity, largely determines …


Genomic Perspectives On Evolution In Bracken Fern, Joshua P. Der May 2010

Genomic Perspectives On Evolution In Bracken Fern, Joshua P. Der

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The fern genus Pteridium comprises a number of closely related species distributed throughout the world. Collectively they are called bracken ferns and have historically been treated as a single species, Pteridium aquilinum. Bracken is notorious as a toxic weed that colonizes open fields and poisons livestock. Bracken is also easily cultured and has become one of the most intensively studied ferns. Bracken has been used as a model system for the study of the fern life cycle, fern gametophyte development, the pheromonal mechanism of sex determination, toxicology, invasion ecology, and climate change. This dissertation places bracken within a global …


The Role Of Ecdysone Signaling In Fat-Body Tissue Remodeling And Pupal Metabolism, Nichole Dinell Bond May 2010

The Role Of Ecdysone Signaling In Fat-Body Tissue Remodeling And Pupal Metabolism, Nichole Dinell Bond

UNLV Theses, Dissertations, Professional Papers, and Capstones

Holometabolous insects undergo an astonishing transition during their development. During metamorphosis, the larva dramatically changes form and becomes an adult fly. During this process obsolete larval tissues must be eliminated, while tissues required for further development are retained and often remodeled to meet the needs of the adult fly. Tissue remodeling is characterized by morphological changes of the cells in a tissue mass. In many cases, remodeling is characterized by dissociation of the tissue mass, releasing cells to move freely around the body cavity. This process is also common in wound healing and is a key feature of human disease …


Effect Of Inflorescence Size On Female Choice In Wild Radish, Raphanus Raphanistrum, Mylenne H. Salinas May 2010

Effect Of Inflorescence Size On Female Choice In Wild Radish, Raphanus Raphanistrum, Mylenne H. Salinas

Renée Crown University Honors Thesis Projects - All

Sexual selection is an important mechanism of speciation. Originally studied in animals, researchers now argue that plants also exhibit characteristics that have been altered by sexual selection. Flower size, nectar production, pollen load, flower scent, and petal color are plant traits that participate in attracting mates through an intermediate pollinator. Although female choice has been demonstrated to enhance offspring quality in animals, a thorough analysis remains to be conducted in plants. In this study, I experimentally altered female choice by manipulating flower number on the hermaphroditic plant, Raphanus raphanistrum. Plants with smaller floral displays had reduced female choice; thus, allowing …


Lineage-Specific Patterns Of Functional Diversification In The Α- And Β-Globin Gene Families Of Tetrapod Vertebrates, Federico G. Hoffmann, Jay F. Storz, Thomas A. Gorr, Juan C. Opazo May 2010

Lineage-Specific Patterns Of Functional Diversification In The Α- And Β-Globin Gene Families Of Tetrapod Vertebrates, Federico G. Hoffmann, Jay F. Storz, Thomas A. Gorr, Juan C. Opazo

Jay F. Storz Publications

The α- and β-globin gene families of jawed vertebrates have diversified with respect to both gene function and the developmental timing of gene expression. Phylogenetic reconstructions of globin gene family evolution have provided suggestive evidence that the developmental regulation of hemoglobin synthesis has evolved independently in multiple vertebrate lineages. For example, the embryonic β-like globin genes of birds and placental mammals are not 1:1 orthologs. Despite the similarity in developmental expression profiles, the genes are independently derived from lineage-specific duplications of a β-globin pro-ortholog. This suggests the possibility that other vertebrate taxa may also possess distinct repertoires of globin genes …


Analysis Of Variation In Clubfoot Candidate Genes, Audrey R. Ester May 2010

Analysis Of Variation In Clubfoot Candidate Genes, Audrey R. Ester

Dissertations and Theses (Open Access)

Isolated clubfoot, a common birth defect occurring in more than 135,000 livebirths worldwide each year, is associated with significant health care and financial burdens. Clubfoot is defined by forefoot adduction, hindfoot varus, midfoot cavus and hindfoot equinus. Isolated clubfoot, which is the focus of these studies, is distinct from syndromic clubfoot because there are no other associated malformations. Population, family, twin and segregation analysis studies provide evidence that genetic and environmental factors play an etiologic role in isolated clubfoot. The studies described in this thesis were performed to define the role of genetic variation in isolated clubfoot. Interrogation of a …


Damage-Induced Inflammation And Nociceptive Hypersensitivity In Drosophila Larvae, Daniel T. Babcock May 2010

Damage-Induced Inflammation And Nociceptive Hypersensitivity In Drosophila Larvae, Daniel T. Babcock

Dissertations and Theses (Open Access)

Mounting an effective response to tissue damage requires a concerted effort from a number of systems, including both the immune and nervous systems. Immune-responsive blood cells fight infection and clear debris from damaged tissues, and specialized pain receptors become hypersensitive to promote behavior that protects the damaged area while it heals. To uncover the cellular and molecular mechanisms underlying these processes, we have developed a genetically tractable invertebrate model of damage-induced inflammation and pain hypersensitivity using Drosophila larvae.

To study wound-induced inflammation, we generated transgenic larvae with fluorescent epidermal cells and blood cells (hemocytes). Using live imaging, we monitored the …


A New Tumor Suppressor Gene Candidate Regulated By The Non-Coding Rna Pca3 In Human Prostate Cancer, Alessandro K. Lee May 2010

A New Tumor Suppressor Gene Candidate Regulated By The Non-Coding Rna Pca3 In Human Prostate Cancer, Alessandro K. Lee

Dissertations and Theses (Open Access)

Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the practice of medicine have allowed a significant improvement in the diagnosis and treatment of this disease and, in recent years, both incidence and mortality rates have been slightly declining. However, it is still estimated that 1 man in 6 will be diagnosed with prostate cancer during his lifetime, and 1 man in 35 will die of the disease.

In order to identify novel strategies and effective therapeutic approaches in the fight against prostate cancer, it …


The Consequences Of Disrupting The Mdm2-P53 Balance In Hematopoiesis, Hussein A. Abbas May 2010

The Consequences Of Disrupting The Mdm2-P53 Balance In Hematopoiesis, Hussein A. Abbas

Dissertations and Theses (Open Access)

The bone marrow accommodates hematopoietic stem cells and progenitors. These cells provide an indispensible resource for replenishing the blood constituents throughout an organism’s life. A tissue with such a high turn-over rate mandates intact cycling checkpoint and apoptotic pathways to avoid inappropriate cell proliferation and ultimately the development of leukemias. p53, a major tumor suppressor, is a transcription factor that regulates cell cycle, and induces apoptosis and senescence. Mice inheriting a hypomorphic p53 allele in the absence of Mdm2, a p53 inhibitor, have elevated p53 cell cycle activity and die by postnatal day 13 due to hematopoietic failure. Hematopoiesis progresses …


Attitudes Of Parents At Risk Of Inheriting Li-Fraumeni Syndrome To Wards Predictive Genetic Testing In Their Minor-Aged Children., Leslie A. Newman May 2010

Attitudes Of Parents At Risk Of Inheriting Li-Fraumeni Syndrome To Wards Predictive Genetic Testing In Their Minor-Aged Children., Leslie A. Newman

Dissertations and Theses (Open Access)

Li-Fraumeni Syndrome (LFS) is a hereditary cancer syndrome which predisposes individuals to cancer beginning in childhood. These risks are spread across a lifetime, from early childhood to adulthood. Mutations in the p53 tumor suppressor gene are known to cause the majority of cases of LFS. The risk for early onset cancer in individuals with Li-Fraumeni Syndrome is high. Studies have shown that individuals with LFS have a 90% lifetime cancer risk. Children under 18 have up to a 15% chance of cancer development. Effectiveness of cancer screening and management in individuals with Li-Fraumeni Syndrome is unclear. Screening for LFS-associated cancers …


Factors Associated With Early Versus Late Development Of Breast And Ovarian Cancer In Brca1 And Brca2 Positive Women, Justine M. Cooper May 2010

Factors Associated With Early Versus Late Development Of Breast And Ovarian Cancer In Brca1 And Brca2 Positive Women, Justine M. Cooper

Dissertations and Theses (Open Access)

Hereditary breast and ovarian cancer (HBOC) is caused by a mutation in the BRCA1 or BRCA2 genes. Women with a BRCA1/2 mutation are at increased risks for breast and ovarian cancer and often develop cancer at an earlier age than the general population. However, some women with a BRCA1/2 mutation do not develop breast or ovarian cancer under the age of 50 years. There have been no specific studies on BRCA positive women with no cancer prior to age 50, therefore this study sought to investigate factors within these women with no cancer under age 50 with respect to reproductive …


Mapping Quantitative Trait Loci Associated With Chilling Requirement And Bloom Date In Peach, Shenghua Fan May 2010

Mapping Quantitative Trait Loci Associated With Chilling Requirement And Bloom Date In Peach, Shenghua Fan

All Dissertations

Chilling requirement (CR), together with heat requirement (HR), determines bloom date (BD), which impacts climatic distribution of genotypes of temperate tree species. The molecular basis of floral bud CR is poorly understood despite its importance to fruit tree adaptation and production. A peach F2 populations developed from two genotypes with contrasting CR values was used for QTL mapping for CR, HR and BD. Using the Contender × Fla.92-2c population, 20 QTLs with additive effects were identified for three traits including one major QTL for CR and two major QTLs for BD. Particularly, one genomic region of 2cM pleiotropic for the …


The Genetics Of Chilling Requirement In Apricot (Prunus Armeniaca L.), Bode Olukolu May 2010

The Genetics Of Chilling Requirement In Apricot (Prunus Armeniaca L.), Bode Olukolu

All Dissertations

Commercial production of apricot is severely affected by sensitivity to climatic conditions, an adaptive feature essential for cycling between vegetative or floral growth and dormancy. Yield losses are due to either late winter or early spring frosts or inhibited vegetative or floral growth caused by unfulfilled chilling requirement (CR). Studies in this dissertation developed the first high-density apricot linkage map; followed by a comparative mapping strategy to validate conservation of synteny, genome collinearity and stable quantitative trait loci (QTLs) controlling CR and bud break between apricot and peach; and ultimately attempt to identify key candidate genes following a linkage disequilibrium-based …


The Population Genetics Of The Endangered Scalloped Hammerhead Shark, Sphyrna Lewini, Across Its Eastern Pacific Range, Holly Nance May 2010

The Population Genetics Of The Endangered Scalloped Hammerhead Shark, Sphyrna Lewini, Across Its Eastern Pacific Range, Holly Nance

All Dissertations

I have characterized the population genetic structure, inferred the evolutionary processes shaping it, and estimated effective population size (Ne) using different contemporary and coalescent methods in the endangered scalloped hammerhead shark, Sphyrna lewini, throughout its Eastern Pacific (EP) range. I found significant genetic differentiation among seven coastal sites between Mexico and Ecuador using 15 microsatellite loci, and significant isolation by distance among samples of mtDNA control region haplotypes. While Bayesian statistical analyses and coalescent-based methods revealed low levels of ecological connectivity between most sampled sites (point estimates of Nm = 0.6 - 7.3), mismatch analyses showed that all populations experienced …


Molecular Analysis Of B3galtl In A Patient With Peters' Plus Syndrome, Taiyabah Naeem Apr 2010

Molecular Analysis Of B3galtl In A Patient With Peters' Plus Syndrome, Taiyabah Naeem

Undergraduate University Honors Capstones

Chromosomal rearrangement such as microdeletions or microduplications, which can alter the dosage of one or more genes, are commonly seen in patients with multiple congenital anomalies (MCA). Alternatively, the discovery of a microdeletion may sometimes uncover an autosomal recessive disorder if the gene on the non-deleted allele carries a mutation. This study reports molecular analysis of a patient with MCAs, including an enlarged head, developmental delay, clouding of the corneas, and short stature. Peters Plus Syndrome (PPS) is characterized as an autosomal recessive disorder. Phenotypical symptoms include various eye abnormalities and structural organ defects. The B3GGALTL has been found to …


Functional Characterization Of Mat1-1-Specific Mating-Type Genes In The Homothallic Ascomycete Sordaria Macrospora Provides New Insights Into Essential And Nonessential Sexual Regulators, V. Klix, M. Nowrousian, C. Ringelberg, J. J. Loros Apr 2010

Functional Characterization Of Mat1-1-Specific Mating-Type Genes In The Homothallic Ascomycete Sordaria Macrospora Provides New Insights Into Essential And Nonessential Sexual Regulators, V. Klix, M. Nowrousian, C. Ringelberg, J. J. Loros

Dartmouth Scholarship

Mating-type genes in fungi encode regulators of mating and sexual development. Heterothallic ascomycete species require different sets of mating-type genes to control nonself-recognition and mating of compatible partners of different mating types. Homothallic (self-fertile) species also carry mating-type genes in their genome that are essential for sexual development. To analyze the molecular basis of homothallism and the role of mating-type genes during fruiting-body development, we deleted each of the three genes, SmtA-1 (MAT1-1-1), SmtA-2 (MAT1-1-2), and SmtA-3 (MAT1-1-3), contained in the MAT1-1 part of the mating-type locus of the homothallic ascomycete species Sordaria macrospora. Phenotypic analysis of deletion mutants revealed …


The Rho Family Gtpase: Determining Gef Specificity Through Recombinant Expression, Farrah Steinke Apr 2010

The Rho Family Gtpase: Determining Gef Specificity Through Recombinant Expression, Farrah Steinke

Honors Capstones

Capstone submitted as a graduation requirement for the BSU Honors Program.


Temporal Regulation Of The Muscle Gene Cascade By Macho1 And Tbx6 Transcription Factors In Ciona Intestinalis, Jamie E. Kugler, Stefan Gazdoiu, Izumi Oda-Ishii, Yale J. Passamaneck, Albert J. Erives, Anna Di Gregorio Apr 2010

Temporal Regulation Of The Muscle Gene Cascade By Macho1 And Tbx6 Transcription Factors In Ciona Intestinalis, Jamie E. Kugler, Stefan Gazdoiu, Izumi Oda-Ishii, Yale J. Passamaneck, Albert J. Erives, Anna Di Gregorio

Dartmouth Scholarship

For over a century, muscle formation in the ascidian embryo has been representative of 'mosaic' development. The molecular basis of muscle-fate predetermination has been partly elucidated with the discovery of Macho1, a maternal zinc-finger transcription factor necessary and sufficient for primary muscle development, and of its transcriptional intermediaries Tbx6b and Tbx6c. However, the molecular mechanisms by which the maternal information is decoded by cis-regulatory modules (CRMs) associated with muscle transcription factor and structural genes, and the ways by which a seamless transition from maternal to zygotic transcription is ensured, are still mostly unclear. By combining misexpression assays with CRM analyses, …


Optimization Algorithms For Functional Deimmunization Of Therapeutic Proteins, Andrew S. Parker, Wei Zheng, Karl E. Griswold, Chris Bailey-Kellogg Apr 2010

Optimization Algorithms For Functional Deimmunization Of Therapeutic Proteins, Andrew S. Parker, Wei Zheng, Karl E. Griswold, Chris Bailey-Kellogg

Dartmouth Scholarship

To develop protein therapeutics from exogenous sources, it is necessary to mitigate the risks of eliciting an anti-biotherapeutic immune response. A key aspect of the response is the recognition and surface display by antigen-presenting cells of epitopes, short peptide fragments derived from the foreign protein. Thus, developing minimal-epitope variants represents a powerful approach to deimmunizing protein therapeutics. Critically, mutations selected to reduce immunogenicity must not interfere with the protein's therapeutic activity.