Increased expression of the human telomere reverse transcriptase (hTERT) in tumors promotes tumor cell survival and diminishes the survival of patients. Cytosine-to-thymine (C-to-T) transition mutations (C250T or C228T) in the promoter create binding sites for transcription factors, which enhance transcription. The G-rich strand of the promoter can form G-quadruplex structures, whereas the C-rich strand can form an i-motif in which multiple cytosine residues are protonated.
View Article and Find Full Text PDFAlthough genomic DNA is predominantly duplex under physiological conditions, particular sequence motifs can favor the formation of alternative secondary structures, including the G-quadruplex. These structures can exist within gene promoters, telomeric DNA, and regions of the genome frequently found altered in human cancers. DNA is also subject to hydrolytic and oxidative damage, and its local structure can influence the type of damage and its magnitude.
View Article and Find Full Text PDFRecently, we constructed a hybrid thymine DNA glycosylase (hyTDG) by linking a 29-amino acid sequence from the human thymine DNA glycosylase with the catalytic domain of DNA mismatch glycosylase (MIG) from , increasing the overall activity of the glycosylase. Previously, it was shown that a tyrosine to lysine (Y126K) mutation in the catalytic site of MIG could convert the glycosylase activity to a lyase activity. We made the corresponding mutation to our hyTDG to create a hyTDG-lyase (Y163K).
View Article and Find Full Text PDFThe DNA of all living organisms is persistently damaged by endogenous reactions including deamination and oxidation. Such damage, if not repaired correctly, can result in mutations that drive tumor development. In addition to chemical damage, recent studies have established that DNA bases can be enzymatically modified, generating many of the same modified bases.
View Article and Find Full Text PDFDNA damage drives genetic mutations that underlie the development of cancer in humans. Multiple pathways have been described in mammalian cells which can repair this damage. However, most work to date has focused upon single lesions in DNA.
View Article and Find Full Text PDFVibrio vulnificus is a naturally occurring, potentially lethal pathogen found in coastal waters, fish, and shellfish. Sewage spills in coastal waters occur when infrastructure fails due to severe storms or age, and may affect bacterial populations by altering nutrient levels. This study investigated effects of sewage on clonal and natural V.
View Article and Find Full Text PDFAims: Beach water quality is regulated by faecal indicator bacteria levels, sand is not, despite known human health risk from exposure to beach sand. We compared the performance of three methods to extract bacterial DNA from beach sand as a step toward a standard method.
Methods And Results: The analytical sensitivity of quantitative polymerase chain reaction (qPCR) for Enterococcus was compared for the slurry (suspension, agitation, membrane filtration of supernatant), versus direct extraction using PowerSoil™ or PowerMax Soil™ kits.
Microbiol Resour Announc
July 2019
The chromosomal methylation statuses of the highly virulent strain CMCP6 grown in human serum and in seawater are compared here. Growth in seawater resulted in ∼4 times as much methylation as that in human serum, primarily N-methylcytosines.
View Article and Find Full Text PDFChemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome sequences confirm their membership in a deeply branching clade of the Gammaproteobacteria. Several adaptations to heterogeneous habitats are apparent.
View Article and Find Full Text PDFBackground: Public disclosure of scientific data used by the government to make regulatory decisions for chemicals is a practical step that can enhance public confidence in the scientific basis of such decisions.
Objectives: We reviewed the U.S.
Environ Health Perspect
June 2011
Objectives: We examined the extent to which consensus exists on the criteria that should be used for assessing the credibility of a scientific work, regardless of its funding source, and explored how these criteria might be implemented.
Data Sources: Three publications, all presented at a session of the 2009 annual meeting of the Society for Risk Analysis, have proposed a range of criteria for evaluating the credibility of scientific studies. At least two other similar sets of criteria have recently been proposed elsewhere.
Environ Health Perspect
January 2008
This article originated from a conference that asked "Should scientific work conducted for purposes of advocacy before regulatory agencies or courts be judged by the same standards as science conducted for other purposes?" In the article, which focuses on the regulatory advocacy context, we argue that it can be and should be. First, we describe a set of standards and practices currently being used to judge the quality of scientific research and testing and explain how these standards and practices assist in judging the quality of research and testing regardless of why the work was conducted. These standards and practices include the federal Information Quality Act, federal Good Laboratory Practice standards, peer review, disclosure of funding sources, and transparency in research policies.
View Article and Find Full Text PDFEnviron Health Perspect
February 2006
The chemical industry extensively researches and tests its products to implement product stewardship commitments and to ensure compliance with governmental requirements. In this commentary we argue that a wide variety of mechanisms enable policymakers and the public to assure themselves that studies performed or funded by industry are identified as such, meet high scientific standards, and are not suppressed when their findings are adverse to industry's interests. The more a given study follows these practices and standards, the more confidence one can place in it.
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