We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as
B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity
of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general
mechanistic significance of the...
Xenobiotic exposures may induce alternative splicing in the pre-mRNA of nuclear hormone receptor (NHR) genes, yielding unpredictable patterns of gene expression that may promote adverse drug events and promote environmental disease. Informed by observations in the androgen receptor (AR; class I NHR), whereby alternatively-spliced AR transcripts induce ligand-independent hormone signaling...
We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as
B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity
of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general
mechanistic significance of the...
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Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping
We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as
B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity
of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general
mechanistic significance of the...
Antisense oligonucleotide (AO)-mediated exon-skipping therapeutics shows great promise in correcting frame-disrupting mutations in the DMD gene for Duchenne muscular dystrophy. However, insufficient systemic delivery limits clinical adoption. Previously, we showed that a glucose/fructose mixture augmented AO delivery to muscle in mdx mice. Here, we evaluated if fructose alone could enhance...
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presented as fold change relative to saline. (c) RT-PCR
analysis to detect dystrophin exon-skipping
Antisense oligonucleotide (AO)-mediated exon-skipping therapeutics shows great promise in correcting frame-disrupting mutations in the DMD gene for Duchenne muscular dystrophy. However, insufficient systemic delivery limits clinical adoption. Previously, we showed that a glucose/fructose mixture augmented AO delivery to muscle in mdx mice. Here, we evaluated if fructose alone could enhance...
Full Text:
oligonucleotide
(AO)-mediated exon-skipping therapeutics is promising for
DMD patients based on encouraging
Antisense oligonucleotide (AO)-mediated exon-skipping therapeutics shows great promise in correcting frame-disrupting mutations in the DMD gene for Duchenne muscular dystrophy. However, insufficient systemic delivery limits clinical adoption. Previously, we showed that a glucose/fructose mixture augmented AO delivery to muscle in mdx mice. Here, we evaluated if fructose alone could enhance...
Exon skipping is capable of correcting frame-shift and nonsense mutations of
Duchenne Muscular Dystrophy (DMD). Phase II clinical trials in UK and Netherlands
have reported induction of dystrophin expression in muscles of DMD patients by
systemic administrations of both phosphorodiamidate morpholino oligomers (PMO)
and 2’O methyl phosphorothioate. Peptide-conjugated PMO (PPMO)...
Antisense morpholino oligomers are synthetic macromolecules can modify gene expression. While these compounds have great potential to treat a broad range of human diseases, they suffer from poor cellular delivery. Conjugating cell-penetrating peptides onto these morpholinos is one option of addressing delivery, however development remains slow due to the cost...
The BRAF proto-oncogene is a member of the Raf protein family that encodes serine/threonine protein kinases, which activate the MEK/ERK signaling transduction pathway. The V600E mutation of BRAF, found in 70% of melanoma cases, causes an upregulation of MEK/ERK signaling which leads to many hallmarks of cancer, including apoptosis evasion,...
Background: Recent mapping of eukaryotic transcriptomes and spliceomes using massively parallel RNA sequencing (RNA-seq) has revealed that the extent of alternative splicing has been considerably underestimated. Evidence also suggests that many pre-mRNAs undergo unproductive alternative splicing resulting in incorporation of in-frame premature termination codons (PTCs). The destinies and potential functions...
BACKGROUND: Targeted capture of genomic regions reduces sequencing cost while generating higher coverage by
allowing biomedical researchers to focus on specific loci of interest, such as exons. Targeted capture also has the
potential to facilitate the generation of genomic data from DNA collected via saliva or buccal cells. DNA samples...
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Mb human All-Exon design and se-
quenced with the Illumina GAII machine and a replication
batch
Morpholino oligos (Morpholinos) are widely used tools for knocking down gene expression and are currently in a clinical trial for treatment of Duchene muscular dystrophy. A Morpholino analog has been in a clinical trial as a potential anti-bioterrorism agent for inhibiting replication of deadly Marburg viral infection. The cellular uptake...
The transition of mature pollen to the progamic phase represents an important step in the regulation of plant sexual reproduction. The progamic phase encompasses the initiation of pollen tube germination, growth of the pollen tube through the stigma (the silk in maize) and concludes with fertilization of the female gametophyte....
Vitamin E (VitE) is necessary for vertebrate embryonic development. VitE prevents lipid peroxidation (LPO), which requires detoxification by cellular antioxidant systems subsequently involving reducing power derived from energy metabolism. Thus, VitE protects metabolic networks in the developing embryo and the integrated gene expression networks compensating for and impaired by LPO-induced...
Pseudoperonospora cubensis is an obligate pathogen and
causative agent of cucurbit downy mildew. To help advance
our understanding of the pathogenicity of P. cubensis, we
used RNA-Seq to improve the quality of its reference
genome sequence. We also characterized the RNA-Seq
dataset to inventory transcript isoforms and infer alternative
splicing...
Tobiano is a dominant pattern of white spotting that occurs in certain breeds of horses. This pattern is often desirable and some breeders will purchase a genetic test to help distinguish homozygous from heterozygous horses for breeding purposes. Some tobiano horses have smaller dark spots on the white patches of...
The immune toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been studied for over 35 years, but only recently has the profound immune suppression associated with TCDD exposure been linked to induction of regulatory T cells (Tregs). The effects of TCDD are mediated through binding the aryl hydrocarbon receptor (AhR), a ligand-activated transcription...
Oomycetes are some of the most devastating pathogens, causing upwards of billions of dollars of damage each year to plants. They also diminish ecological diversity and health through the destruction of trees and shrubs. The genome sequence of Pseudoperonospora cubensis, an obligate plant pathogen and causative agent of downy mildew...
DNA damage, if not repaired, can become a mutation. Mutation
accumulation is associated with initiation and progression of tumorigenesis. DNA
mismatch repair (MMR) is required for maintaining genetic stability by repairing
replication errors. Biochemical studies have shown that MMR also recognizes
mismatch-causing DNA lesions, suggesting the role of MMR in...
Within the past several years the technology of high-throughput sequencing has transformed the study of biology by offering unprecedented access to life's fundamental building block, DNA. With this transformation's potential a host of brand-new challenges have emerged, many of which lend themselves to being solved through computational methods. From de...
Transcriptomics and gene expression profiling enables the elucidation of the genetic response of an organism to various environmental cues. Transcriptomics enables the deciphering of differences between two closely related organisms to the same environment and in contrast, enables the elucidation of genetic responses of the same organism to different environmental...
Hepatitis E virus (HEV) infection is a cause of hepatitis in humans worldwide. Recently, persistent and chronic HEV infections have been recognized as a serious clinical problem, especially in immunocompromised individuals. To date, there are no FDA-approved HEV-specific antiviral drugs. In this study, we designed and evaluated antisense peptide-conjugated morpholino...
• Premise of the study: The dramatic advances offered by modern DNA sequencers continue to redefine the limits of what can be accomplished in comparative plant biology. Even with recent achievements, however, plant genomes present obstacles that can make it difficult to execute large-scale population and phylogenetic studies on next-generation...
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compatibility complex (MHC) exon in 79 bank vole accessions.
Notably, while Babik et al. (2009) predicted
Rice is an important crop that feeds almost half the world population. As climate change models predict floods, drought and extreme temperatures in rice production areas, the need to better understand the genetic basis of adaptation and tolerance to abiotic and biotic stresses is vital to sustain our food supply....
Signal transduction within and between cells is at the core of biological activity in all living systems. Signaling networks are required for regulating biological functions, including growth, development and survival. Deregulation of signaling cascades has been linked to chronic and acute diseases and disorders This thesis focuses on mass spectrometry...
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upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a
Cystic fibrosis is an inherited genetic disease caused by a single gene mutation in the CFTR protein. Affecting 70,000 people worldwide, this disease is debilitating to patients, resulting in persistent lung infections and decreased quality of life. Due to the various mutation types, there is not currently a single drug...
The work presented in this dissertation examines possible
modes of action for growth inhibition by anthropogenic endocrine
disrupting chemicals (EDCs) as well as endogenous hormones
associated with growth in fish. Using the sheepshead minnow (SHM)
(Cyprinodon variegatus) as a model, I developed methods to examine
perturbations in the endocrine axis...
The first goal of this study was to evaluate the roles of different intracellular
proteolytic systems in accelerated skeletal muscle protein degradation. Total,
myofibrillar and non-myofibrillar proteolysis were determined in cultured L8/CID
muscle cells. Calpain proteolysis was assessed by over-expressed calpastatin inhibitory
domain (CD). Lysosomal proteolysis was determined in the...
All animals have developed the critical ability to detect, respond to, and detoxify a large array of environmental chemicals and stressors that can cause adverse health effects. Important examples of landmark contaminants around the world are polycyclic aromatic hydrocarbons (PAHs) and dioxins, both of which can act via the aryl...
European hazelnut (Corylus avellana L.) is an important crop Oregon's Willamette Valley, producing 99% of the hazelnuts grown in North America and brings over US $60 million dollars to the region annually. Hazelnuts are rich in fiber and vitamins, as well in demand by consumers due to their popularity as...
Symbiosis is the close and protracted interaction between organisms. The molecular interactions that occur during symbiosis are complex with multiple barriers that must be overcome. Many Gram-negative, host-associated bacteria use a type III secretion system to mediate associations with their eukaryotic hosts. This secretion system is a specialized apparatus for...