bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactions do not only tell us when, but can also tell us how: Testing process hypotheses by interaction
Authors: Jacoby Johann , Sassenberg Kai 
Published: August 2010

AbstractHypotheses about psychological processes are often tested using traditional mediation analysis. This analysis relies on measurement of a transmitting variable. Conducting this analysis has become almost synonymous with examining process hypotheses. An alternative strategy to mediation analysis (the Testing‐a‐Process‐hypothesis‐by‐an‐Interaction Strategy, TPIS) is illustrated here. TPIS is based on a fully experimental design whereby a hypothesized process is tested by an interaction between the hypothesized cause of an effect and a contextual variable. In the interaction term, the contextual variable allows comparison of the causal effect observed when the process is uninterrupted to the effect observed when the process is interrupted. Thus, TPIS translates a theoretical process hypothesis into a statistical interaction hypothesis that uses a fully experimental design to directly examine the hypothesized process. Copyright © 2010 John Wiley & Sons, Ltd.
Determination of free bilirubin and its binding capacity by HSA using a microfluidic chip‐capillary electrophoresis device with a multi‐segment circular‐ferrofluid‐driven micromixing injection
Authors: Sun Hui , Nie Zhou , Fung Ying Sing 
Published: August 2010

AbstractA PMMA microfluidic chip‐CE device with a multi‐segment circular‐ferrofluid‐driven micromixing injector has been developed for the determination of free bilirubin and its binding capacity by HSA at equilibrium. The design of the device and its fabrication by a low cost CO2laser are discussed for intended applications. Under optimized conditions, the total binding capacity of HSA for bilirubin was determined as 16.3±1.4 mg/l00 mL human serum (n=3) and residual binding capacity for bilirubin 9.8 mg/l00 mL (n=3) in normal infants. To assess risk of hyperbilirubinemia, free bilirubin and residual binding capacity by HSA provide a better indicator than total bilirubin, as neonates with impaired bilirubin binding capacity could be detected. In addition, residual binding capacity provides an advanced indicator to predict the onset of hyperbilirubinemia before the appearance of free bilirubin. HSA down to 94 nL is used in each titration and a full assay of four titrations takes up 376 nL HSA, sufficient for newborns with HSA in microliter range. The device has shown capable to provide adequate margin of protection to detect an early rising level of bilirubin and impaired binding capacity prior to the onset of jaundice condition.
Development of neurons on micropatterns reveals that growth cone responds to a sharp change of concentration of laminin
Authors: Xing Shige , Liu Wenwen , Huang Zhuo , Chen Long , Sun Kang , Han Dong , Zhang Wei , Jiang Xingyu 
Published: August 2010

AbstractIn this report we fabricated laminin (LN) stripes on a background of poly‐L‐lysine as substrates for the growth of rat hippocampal neurons, and found that a sharp change of the concentration of LN guides the growth of neurites by leading the growth cones in a time‐ and space‐dependent manner. The percentage of neurites that grow along the edge of LN stripes (where there is a sharp change of concentration) decreases as a function of the concentration of LN under a threshold value. The actin cytoskeleton plays an important role in the process of growth cone's response to the sharp change of concentration of LN on micropatterns. We believe that the findings here are useful for not only fundamental studies in neuroscience, but also helpful for the design of devices or chips for nervous prosthesis.
Differential methylation of CpG sites in two isoforms of myosin binding protein C, an important hypertrophic cardiomyopathy gene
Authors: Meurs Kathryn M. , Kuan Mani 
Published: August 2010

AbstractHypertrophic cardiomyopathy (HCM) is a common form of cardiac disease. Over 400 causative mutations have been identified in 20 sarcomere and myofilament related genes. The high density of mutations found in genes associated with HCM may suggest that mechanisms promoting increased mutability play a role in disease prevalence. The objective of this study was to evaluate the CpG methylation level of the exonic regions of the cardiac myosin binding protein C gene (MYBPC3), a common causal gene for HCM. To determine if the methylation level is gene specific and possibly involved with gene mutability, we also evaluated the methylation of the CpGs within the exonic regions of the skeletal muscle isoform of the myosin binding protein C gene (MYBPC2); there are no known mutations that lead to the development of familial human disease within this gene. We determined that although the mean number of CG sites was identical within the coding region of each gene, the mean methylation level of CpGs was significantly higher inMYBPC3thanMYBPC2(P< 0.0001). The results of this study suggest that there are unique aspects of this cardiac gene or its epigenetic environment which may result in increased genetic mutability. Evaluation of the methylation levels of additional causal cardiomyopathic genes is warranted. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.
Oncomutations as biomarkers of cancer risk
Authors: Parsons Barbara L. , Myers Meagan B. , Meng Fanxue , Wang Yiying , McKinzie Page B. 
Published: August 2010

AbstractCancer risk assessment impacts a range of societal needs, from the regulation of chemicals to achieving the best possible human health outcomes. Because oncogene and tumor suppressor gene mutations are necessary for the development of cancer, such mutations are ideal biomarkers to use in cancer risk assessment. Consequently, DNA‐based methods to quantify particular tumor‐associated hotspot point mutations (i.e., oncomutations) have been developed, including allele‐specific competitive blocker‐PCR (ACB‐PCR). Several studies using ACB‐PCR and model mutagens have demonstrated that significant induction of tumor‐associated oncomutations are measureable at earlier time points than are used to score tumors in a bioassay. In the particular case of benzo[a]pyrene induction of K‐Ras codon 12 TGT mutation in the A/J mouse lung, measurement of tumor‐associated oncomutation was shown to be an earlier and more sensitive endpoint than tumor response. The measurement of oncomutation by ACB‐PCR led to two unexpected findings. First, oncomutations are present in various tissues of control rodents and “normal” human colonic mucosa samples at relatively high frequencies. Approximately 60% of such samples (88/146) have mutant fractions (MFs) >10−5, and some have MFs as high as 10−3 or 10−4. Second, preliminary data indicate that oncomutations are present frequently as subpopulations in tumors. These findings are integrated into a hypothesis that the predominant preexisting mutations in particular tissues may be useful as generic reporters of carcinogenesis. Future research opportunities using oncomutation as an endpoint are described, including rodent to human extrapolation, dose‐response assessment, and personalized medicine. Environ. Mol. Mutagen., 2010. Published 2010 Wiley‐Liss, Inc.
Historical perspective on the development of the genetic toxicity test battery in the United States
Authors: Zeiger Errol 
Published: August 2010

AbstractThe currently used genetic toxicity testing battery (the Ames Salmonella test, the in vitro mammalian cell mouse lymphoma assay and/or the in vitro mammalian cell chromosome assay, and the rodent bone marrow chromosome aberration or micronucleus assay) had its origins in the early‐to‐mid 1970s. By the late 1970s, a large number of genetic tests had been proposed or recommended by the US‐EPA for identifying germ cell mutagens and carcinogens. After a number of modifications that were primarily directed toward minimizing the number of tests used, the test battery reached its current state in the mid‐1980s. This test battery, with some minor modifications in the timing or ordering of the tests is mandated by regulatory authorities worldwide. Although it would be intellectually satisfying to presume that this compendium of tests was developed and selected for regulatory screening based solely on scientific grounds, it was actually based on a combination of scientific data, theoretical considerations, chance, and advocacy, and not always in equal proportions. The evolution of the current genetic toxicity test battery, and some of the activities and considerations that directed this evolution are described. Environ. Mol. Mutagen., 2010. © 2010 Wiley‐Liss, Inc.
Proposal of an in vivo comet assay using haemocytes of Drosophila melanogaster
Authors: Carmona Erico R. , Guecheva Temenouga N. , Creus Amadeu , Marcos Ricardo 
Published: August 2010

AbstractThis study presents the first application of an in vivo alkaline comet assay using haemocytes of Drosophila melanogaster larvae. These cells, which play a role similar to that of mammalian blood, can be easily obtained and represent an overall exposure of the treated larvae. To validate the assay, we evaluated the response of these cells to three well‐known mutagenic agents: ethyl methanesulfonate (EMS), potassium dichromate (PD), and gamma radiation (γ‐irradiation). Third‐instar Drosophila larvae were exposed to different concentrations of EMS (1, 2, and 4 mM) and PD (0.5, 1, and 2.5 mM) and to different doses of γ‐irradiation (2, 4, and 8 Gγ). Subsequently, haemolymph was extracted from the larvae, and haemocytes were isolated by centrifugation and used in the comet assay. Haemocytes exhibited a significant dose‐related increase in DNA damage, indicating that these cells are clearly sensitive to the treatments. These results suggest that the proposed in vivo comet test, using larvae haemocytes of D. melanogaster, may be a useful in vivo assay for genotoxicity assessment. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.
Expression of DNA repair and apoptosis genes in mitochondrial mutant and normal cells following exposure to ionizing radiation
Authors: Kulkarni Rohan , Thomas Robert A. , Tucker James D. 
Published: August 2010

AbstractIn double‐strand DNA damage repair, nonhomologous end joining (NHEJ) is more error‐prone than homologous recombination repair (HRR), indicating that the relative prevalence of NHEJ may lead to more incorrect repair and thus to increases in chromosome damage. If DNA damage is extensive and cells are unable to repair that damage they typically undergo apoptosis. The mechanism(s) by which cells decide to switch from DNA repair to apoptosis is unknown. Since DNA repair and apoptosis are both energy‐demanding processes, the answer may involve ATP utilization. We used human mitochondrial mutant cell lines obtained from people with phenotypic manifestations of compromised ATP generation. We hypothesized that these cells may not have adequate capacity for dealing with the additional demands for ATP required for repairing DNA damage after genotoxic exposure, perhaps making the cells more prone to undergo apoptosis instead of initiating repair. This study describes changes in the expression of genes involved in NHEJ or HRR, as well as genes involved in apoptosis, in one normal and two mitochondrial mutant human cell lines following ionizing radiation exposure. Compared to normal cells, both mutant cell lines showed reduced expression of genes involved in NHEJ and HRR. Analysis of expression changes in genes involved in apoptosis revealed marked increases in expression in the mutants compared to normal cells. These results indicate that following ionizing radiation exposure, mitochondrial mutant cells have decreased levels of mRNA expression of DNA repair genes and increased expression levels of genes involved in apoptosis compared to normal cells. This study provides information that might be useful in characterizing energy dependent processes following exposure to stress or genotoxic agents. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.
Genetics and women's health issues—The commitment of EMS to women scientists and gender‐associated disease topics
Authors: Witt Kristine L. , Moorman Patricia G. , Kovalchuk Olga , Holland Nina , Block Gladys , Andreassen Paul R. 
Published: August 2010

AbstractThis manuscript presents an overview of a symposium held at the 2009 annual meeting of the Environmental Mutagen Society (EMS) in St. Louis, MO. The symposium was sponsored by the Women in the Environmental Mutagen Society (WEMS) special interest group, and it covered current molecular genetics technologies and their impact on diagnosis and treatment of diseases that primarily or differentially affect women. Four speakers presented groundbreaking new information from such areas as cancer genetics, gene‐environment interactions, epigenetics, DNA repair, and molecular epidemiology. Although cancer was a primary focus of the symposium, other health issues such as obesity and cardiovascular disease were addressed. The rapid evolution in genomic technologies discussed in this symposium should provide new tools to explore some of the critical questions raised by the research projects described in this article. This symposium demonstrates that EMS provides a forum for the presentation, discussion, and extension of the data generated by the investigators featured in this article and other researchers engaged in the study of the molecular mechanisms and gene‐environment interactions that impact women's health. Environ. Mol. Mutagen., 2010. © 2010 Wiley‐Liss, Inc.
Growing up with DNA repair and joining the EMS
Authors: Hanawalt Philip 
Published: August 2010

AbstractI recount some personal history, as I rode the crest of the wave of discovery and excitement in the DNA repair field from the early 1960s and eventually came to appreciate that the Environmental Mutagen Society is the appropriate professional “home” for researchers in this field: it places them in the context of the broader genetic, societal, and regulatory issues raised from their studies. In return, the wisdom provided from basic research on cellular processing of damaged DNA is essential to mechanism‐based decisions in the domain of genetic toxicology. Environ. Mol. Mutagen., 2010. Published 2010 Wiley‐Liss, Inc.
Superoxide dismutase protects cells from DNA damage induced by trivalent methylated arsenicals
Authors: Tennant Alan H. , Kligerman Andrew D. 
Published: August 2010

AbstractSuperoxide dismutase (SOD) catalyzes the conversion of superoxide to hydrogen peroxide. Heterozygous mice of strain B6;129S7‐Sod1tm1Leb/J were obtained from Jackson Laboratories and bred to produce offspring that were heterozygous (+/Sod1tm1Leb), homozygous wild‐type (+/+), and homozygous knockout (Sod1tm1Leb/Sod1tm1Leb) for the Cu/Zn superoxide dismutase (Sod1) gene. Splenocytes from these mice were exposed to several concentrations of either sodium arsenite (As3 [0–200 μM]), monomethylarsonous acid (MMA3 [0–10 μM]), or dimethylarsinous acid (DMA3 [0–10 μM]) for 2 hr. Cells were then examined for DNA damage using the alkaline single cell gel electrophoresis assay. Methyl methanesulfonate (MMS) was used as a positive control. Splenocytes from each of the three genotypes for Sod1 were equally sensitive to MMS and As3. However, at equimolar concentrations, DMA3 and MMA3 produced significantly more DNA damage in the homozygous knockout mouse splenocytes than in the splenocytes from the wild‐type or heterozygous mice. These findings suggest that superoxide is involved either directly or indirectly in producing DNA damage in cells exposed to trivalent methylated arsenicals. These arsenicals may generate reactive oxygen species that damage DNA. This DNA damage may be a key factor in initiating cancer in vivo. Environ. Mol. Mutagen., 2011. Published 2010 Wiley‐Liss, Inc.
Antigenotoxic effects of p53 on spontaneous and ultraviolet light B–induced deletions in the epidermis of gpt delta transgenic mice
Authors: Masumura Kenichi , Sakamoto Yasuteru , Ikeda Megumi , Asami Yasuo , Tsukamoto Tetsuya , Ikehata Hironobu , Kuroiwa Yuichi , Umemura Takashi , Nishikawa Akiyoshi , Tatematsu Masae , Ono Tetsuya , Nohmi Takehiko 
Published: August 2010

AbstractTumor development in the skin may be a multistep process where multiple genetic alterations occur successively. The p53 gene is involved in genome stability and thus is referred to as “the guardian of the genome.” To better understand the antigenotoxic effects of p53 in ultraviolet light B (UVB)‐induced mutagenesis, mutations were measured in the epidermis of UVB‐irradiated p53+/+ and p53−/− gpt delta mice. In the mouse model, point mutations and deletions are separately identified by the gpt and Spi− assays, respectively. The mice were exposed to UVB at single doses of 0.5, 1.0, or 2.0 kJ/m2. The mutant frequencies (MFs) were determined 4 weeks after the irradiation. All doses of UVB irradiation enhanced gpt MFs by about 10 times than that of unirradiated mice. There were no significant differences in gpt MFs and the mutation spectra between p53+/+ and p53−/− mice. The predominant mutations induced by UVB irradiation were G:C to A:T transitions at dipyrimidines. In contrast, in unirradiated p53−/− mice, the frequencies of Spi− large deletions of more than 1 kb and complex‐type deletions with rearrangements were significantly higher than those of the Spi− large deletions in p53+/+ counterparts. The specific Spi− mutation frequency of more than 1 kb deletions and complex types increased in a dose‐dependent manner in the p53+/+ mice. However, no increase of such large deletions was observed in irradiated p53−/− mice. These results suggest that the antigenotoxic effects of p53 may be specific to deletions and complex‐type mutations induced by double‐strand breaks in DNA. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.
Germ cell mutagens: Risk assessment challenges in the 21st century
Authors: Singer Timothy M. , Yauk Carole L. 
Published: August 2010

AbstractHeritable mutations may result in a wide variety of detrimental outcomes, from embryonic lethality to genetic disease in the offspring. Despite this, today's commonly used test batteries do not include assays for germ cell mutation. Current challenges include a lack of practical assays and concrete evidence for human germline mutagens, and large data gaps that often impede risk assessment. Moreover, most regulatory assessments are based on the assumption that somatic cell mutation assays also protect the germline by default, which has not been adequately confirmed. The field is also faced with new challenges aimed at dramatically reducing animal testing, and attempts to rapidly classify thousands of chemicals using high throughput in vitro assays. These approaches may not adequately capture effects that may be particular to gametes, since many aspects of the germline are unique. In light of these challenges, an urgent need exists to develop new approaches to evaluate the potential of toxicants to cause germline mutation. The application of new technologies will greatly enhance our understanding of mutation in humans exposed to environmental mutagens. However, we must be poised to collect and interpret these data, and facilitate risk translation to regulators and the public. Genetic toxicologists must also become actively involved in the development of high‐throughput tools to study germline mutation. Appropriate attention to these areas will result in the development of policies that prioritize the protection of the germline and future generations from DNA sequence mutations. Environ. Mol. Mutagen. 2010. © 2010 Government of Canada.
New and emerging technologies for genetic toxicity testing
Authors: Lynch Anthony M. , Sasaki Jennifer C. , Elespuru Rosalie , Jacobson‐Kram David , Thybaud Véronique , De Boeck Marlies , Aardema Marilyn J. , Aubrecht Jiri , Benz R. Daniel , Dertinger Stephen D. , Douglas George R. , White Paul A. , Escobar Patricia A. , Fornace Albert , Honma Masamitsu , Naven Russell T. , Rusling James F. , Schiestl Robert H. , Walmsley Richard M. , Yamamura Eiji , van Benthem Jan , Kim James H. 
Published: August 2010

AbstractThe International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow‐up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing established an Emerging Technologies and New Strategies Workgroup to review the current State of the Art in genetic toxicology testing. The aim of the workgroup was to identify promising technologies that will improve genotoxicity testing and assessment of in vivo hazard and risk, and that have the potential to help meet the objectives of the IVGT. As part of this initiative, HESI convened a workshop in Washington, DC in May 2008 to discuss mature, maturing, and emerging technologies in genetic toxicology. This article collates the abstracts of the New and Emerging Technologies Workshop together with some additional technologies subsequently considered by the workgroup. Each abstract (available in the online version of the article) includes a section addressed specifically to the strengths, weaknesses, opportunities, and threats associated with the respective technology. Importantly, an overview of the technologies and an indication of how their use might be aligned with the objectives of IVGT are presented. In particular, consideration was given with regard to follow‐up testing of positive results in the standard IVGT tests (i.e., Salmonella Ames test, chromosome aberration assay, and mouse lymphoma assay) to add weight of evidence and/or provide mechanism of action for improved genetic toxicity risk assessments in humans. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.
Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes
Authors: Hackenberg Stephan , Friehs Gudrun , Kessler Michael , Froelich Katrin , Ginzkey Christian , Koehler Christian , Scherzed Agmal , Burghartz Marc , Kleinsasser Norbert 
Published: August 2010

AbstractIndustrial application of titanium dioxide nanoparticles (TiO2‐NPs) as an additive in pharmaceutical and cosmetic products is increasing. However, the knowledge about the toxicity of this material is still incomplete and data concerning health and environmental safety and results of recent studies on TiO2 nanotoxicology are inconsistent. The in vitro geno‐ and cytotoxicity of TiO2‐NPs in the anatase crystal phase was evaluated in human peripheral blood lymphocytes from 10 male donors. Initially, transmission electron microscopy (TEM) was performed to describe particle morphology and size, the degree of particle aggregation, and the intracellular distribution. Cells were exposed to nanoparticles in increasing concentrations of 20, 50, 100, and 200 μg/ml for 24 hr. Cytotoxic effects were analyzed by trypan blue exclusion test and the single‐cell microgel electrophoresis (comet) assay was applied to detect DNA double‐strand breakage. TiO2‐NPs were sphere shaped with a diameter of 15–30 nm. Despite dispersive pretreatment, a strong tendency to form aggregates was observed. Particles were detected in the cytoplasm of lymphocytes, but also a transfer into the nucleus was seen. The trypan blue exclusion test did not show any decrease in lymphocyte viability, and there was no evidence of genotoxicity in the comet assay for any of the tested concentrations. In conclusion, TiO2‐NPs reached the cytoplasm as well as the nucleus and did not induce cyto‐ or genotoxic effects in human peripheral blood lymphocytes. Complement investigations on different human cell systems will be performed to estimate the biocompatibility of TiO2‐NPs. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.