Publications by authors named "Tiffany Kaul"

Only a select few L1 loci in the human genome are expressed in any given cell line or organ, likely to minimize damage done to the genome. The epigenetic features and requirements of expressed L1 loci are currently unknown. Using human cells and comprehensive epigenetic analysis of individual expressed and unexpressed L1 loci, we determined that endogenous L1 transcription depends on a combination of epigenetic factors, including open chromatin, activating histone modifications, and hypomethylation at the L1 promoter.

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Expression of L1 mRNA, the first step in the L1 copy-and-paste amplification cycle, is a prerequisite for L1-associated genomic instability. We used a reported stringent bioinformatics method to parse L1 mRNA transcripts and measure the level of L1 mRNA expressed in mouse and rat organs at a locus-specific resolution. This analysis determined that mRNA expression of L1 loci in rodents exhibits striking organ specificity with less than 0.

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Article Synopsis
  • Alu elements are common in the human genome and play a significant role in causing genetic instability, particularly during DNA double-stranded breaks due to their high copy number and characteristics that affect recombination.
  • Using a reporter-gene assay, the study reveals that mismatches between Alu elements can lead to two main outcomes: either nonallelic homologous recombination (HR) or DNA breaks that can cause deletions through alternative repair processes.
  • The formation of these intermediates is dependent on RAD52, and the presence of defects in DNA repair genes like ERCC1 and MSH2 influences the types of deletions associated with Alu elements, which may contribute to different cancer types.
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  • Retrotransposons, especially the L1 element, significantly influence mammalian genomes and human diseases, comprising 17% of the human genome despite most having defects.
  • The study tested RNA-Seq data from prostate cancer cells to compare the quality and effort required for identifying expressed L1, finding minimal data loss with whole-cell, strand-specific RNA-Seq compared to cytoplasmic RNA-Seq, though it required more manual curation.
  • The research concludes that with careful manual curation, both cytoplasmic and whole-cell stranded RNA-Seq datasets can effectively identify expressed L1 loci, even though non-strand-specific datasets result in significant data loss.
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  • Long Interspersed Elements (LINEs/L1s) are repetitive genetic elements that can copy and insert themselves into the genome, causing genomic instability and mutations.
  • There are over 500,000 copies of L1 in the human genome, but 99% are defective, making it difficult to identify actively expressed L1s amidst other similar sequences.
  • The study presents a RNA-Seq bioinformatics method to accurately detect L1 expression at specific loci by analyzing RNA from prostate tumor cells, confirming transcription from individual L1 promoters.
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Article Synopsis
  • - The human genome has a lot of repetitive DNA sequences, which increases the chances for DNA rearrangements between similar segments that aren’t directly inherited from each parent.
  • - To prevent these rearrangements, the genome employs various repair mechanisms that compete and work together to fix any issues that arise.
  • - In cancer cells, some of these DNA repair pathways are weakened, leading to increased occurrences of these harmful DNA rearrangements.
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Dietary restriction (DR) and reduced insulin growth factor (IGF) signaling extend lifespan in Caenorhabditis elegans and other eukaryotic organisms. Autophagy, an evolutionarily conserved lysosomal degradation pathway, has emerged as a central pathway regulated by various longevity signals including DR and IGF signaling in promoting longevity in a variety of eukaryotic organisms. However, the mechanism remains unclear.

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Under adverse environmental conditions the nematode Caenorhabditis elegans can enter an alternate developmental stage called the dauer larva. To identify lipophilic signaling molecules that influence this process, we screened a library of bioactive lipids and found that AM251, an antagonist of the human cannabinoid (CB) receptor, suppresses dauer entry in daf-2 insulin receptor mutants. AM251 acted synergistically with glucose supplementation indicating that the metabolic status of the animal influenced the activity of this compound.

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N-acylethanolamines are an important class of lipid signaling molecules found in many species, including the nematode Caenorhabditis elegans (C. elegans) where they are involved in development and adult lifespan. In mammals, the relative activity of the biosynthetic enzyme N-acyl phosphatidylethanolamine-specific phospholipase-D and the hydrolytic enzyme fatty acid amide hydrolase determine N-acylethanolamine levels.

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The Caenorhabditis elegans dauer larva is a facultative state of diapause. Mutations affecting dauer signal transduction and morphogenesis have been reported. Of these, most that result in constitutive formation of dauer larvae are temperature-sensitive (ts).

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The dauer larva is a specialized dispersal stage in the nematode Caenorhabditis elegans that allows the animal to survive starvation for an extended period of time. The dauer does not feed, but uses chemosensation to identify new food sources and to determine whether to resume reproductive growth. Bacteria produce food signals that promote recovery of the dauer larva, but the chemical identities of these signals remain poorly defined.

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Background: α-synuclein [α-Syn]-mediated activation of GSK-3β leading to increases in hyperphosphorylated Tau has been shown by us to occur in striata of Parkinson's diseased [PD] patients and in animal models of PD. In Alzheimer's disease, tauopathy exists in several brain regions; however, the pattern of distribution of tauopathy in other brain regions of PD or in animal models of PD is not known. The current studies were undertaken to analyze the distribution of tauopathy in different brain regions in a widely used mouse model of PD, the α-Syn overexpressing mouse.

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