Specific Types Of Damage Research Articles

Repair kinetics of specific types of nitroso-induced DNA damage using the comet assay in human cells

The comet assay is sensitive and can detect DNA damage frequencies less than 1 in 10 7 bases. We have previously shown that several types of DNA damage associated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific pro-mutagen, can be investigated with some specificity using this technique. Little is known about their repair. We verified the ability of the comet assay to quantify the repair kinetics of specific types of damage in normal fibroblasts, e.g., dimethylsulfate-induced 7-methylguanines (7-mG) and UVB-induced cyclobutane pyrimidine dimers. The time course, formation and repair, of DNA damage after acute doses of NNK reactive metabolites, were then compared in normal human cells (fibroblasts and lymphocytes) and in cells proficient for activating NNK (U937 and NCI-H23). NNK can be activated in cells into reactive metabolites that can either methylate or pyridyloxobutylate DNA. The 7-mG generated by methylation gave post-treatment patterns that were sufficiently different between cell types to conclude that repair of 7-mG in U937 cells was fast, repair in lymphocytes was slow, and repair in NCI-H23 cells and fibroblasts displayed intermediate rates. Pyridyloxobutylation generated formamidopyrimidine (fapy) glycosylase (fpg)-sensitive sites that could be the fapy form of 7-pyridyloxobutylguanines produced in cells. For this type of adducts, the post-treatment patterns of adduct frequency as a function of time depended even more clearly on the cell type: fibroblasts and NCI-H23 cells showed an initial rapid increase in fpg-sensitive damage frequency that did not occur in lymphocytes and U937 cells. This increase seemed associated with p53 proficiency in fibroblasts. Our results show that repair kinetics can be investigated with the comet assay and that differences between cell types can be observed with that technique. But it seems that pro-mutagen activation and/or the way a type of adducts is formed can affect the quantification of the repair.

Sarcopenia in the Caenorhabditis elegans pharynx correlates with muscle contraction rate over lifespan

In muscles, sarcopenia, the loss of muscle mass, is the major cause of aging-related functional decline and frailty. Several factors are correlated with sarcopenia during aging, including contraction-related cellular injury, oxidative stress, endocrine changes and reduced regenerative potential. However the involvement of these factors has not been experimentally investigated. Here, we report that contraction-related injury may significantly promote the progression of sarcopenia in the pharynx of the nematode, Caenorhabditis elegans, a model of aging in non-regenerative tissues. Both functional and structural declines in the pharynx during aging were significantly delayed in mutants with reduced muscle contraction rates. We also examined the role of bacteria in pharynx muscle decline during aging, as previous studies reported that antimicrobial treatments could extend C. elegans lifespan. Although microbial infection may have enhanced functional decline in the pharynx during aging, it was not the sole cause of decreased pumping rates in old animals. This study identifies contraction-related injury as a factor affecting the initiation and progression of sarcopenia during aging. Further, characterization of the specific types of damage induced by muscle contraction will be helpful for understanding the underlying causes of sarcopenia.

Sensor network paradigms for structural health monitoring

Structural health monitoring (SHM) is the process of detecting damage in structures. The goal of SHM is to improve the safety and reliability of aerospace, civil and mechanical infrastructure by detecting damage before it reaches a critical state. A specific topic that has not been extensively addressed in the SHM literature is the development of rigorous approaches to designing the SHM sensing system that is used to address the data acquisition portion of the problem. To date, almost all such system designs are done somewhat in an ad hoc manner where the engineer picks a sensing system that is readily available and that they are familiar with, and then attempts to demonstrate that a specific type of damage can be detected with that system. In many cases this approach has been shown to be ineffective and as a result researchers have begun to develop sensor networks specially suited for SHM. Based on this research, several sensor network paradigms for SHM have emerged, and this paper is intended to provide an overview of these paradigms. This paper will first provide a brief summary of the statistical pattern recognition approach to SHM problem. The data acquisition portion of the paradigm is then addressed in detail where the various parameters of the system that must be considered in its design and subsequent field deployment are summarized. Published in 2005 by John Wiley & Sons, Ltd.

Damage caused to fibres by the action of two types of heat

Research into the specific types of damage to textiles and singular textile fibres caused by contact with a heating plate at a given temperature and with the open flame of a gas burner is presented. Experiments were carried out using a selection of textiles (fabrics and knits) differing in colour, fibre composition and textile construction. The characteristic changes that occur in different kinds of textiles and fibres after thermal degradation were observed through microscopic examinations—optical and scanning electron microscopy (SEM).

DNA Mismatch Repair Protein Msh6 Is Required for Optimal Levels of Ultraviolet-B-Induced Apoptosis in Primary Mouse Fibroblasts

Recent data support a role for DNA mismatch repair in the cellular response to some forms of exogenous DNA damage beyond that of DNA repair; cells with defective DNA mismatch repair have partial or complete failure to undergo apoptosis and/or G2M arrest following specific types of damage. We propose that the DNA mismatch repair Msh2/Msh6 heterodimer, responsible for the detection of DNA damage, promotes apoptosis in normal cells, thus protecting mammals from ultraviolet-induced malignant transformation. Using primary mouse embryonic fibroblasts derived from Msh6+/+ and Msh6-/- mice, we compare the response of DNA-mismatch repair-proficient and -deficient cells to ultraviolet B radiation. In the wild-type mouse embryonic fibroblasts, ultraviolet-B-induced increases in Msh6 protein levels were not dependent on p53. Msh6-/- mouse embryonic fibroblasts were significantly less sensitive to the cytotoxic effects of ultraviolet B radiation. Further comparison of the Msh6+/+ and Msh6-/- mouse embryonic fibroblasts revealed that Msh6-/- mouse embryonic fibroblasts undergo significantly less apoptosis following ultraviolet B irradiation, thus indicating that ultraviolet-B-induced apoptosis is partially Msh6 dependent. These data support a role for Msh6 in protective cellular responses of primary cells to ultraviolet-B-induced mutagenesis and, hence, the prevention of skin cancer.

Herbivory on Acacia seedlings in an East African savanna

Trees critically affect the functioning of savanna ecosystems through their effects on nutrient cycling, water availability, and patterns of space use by wildlife. Therefore, whatever factors influence successful recruitment of tree seedlings are important filters controlling savanna ecosystem function. In African savannas, large mammals have been considered the most important agents of mortality for adult trees, but their impacts on tree seedlings are not well‐known. Similarly, the effects of rodents and invertebrates as seedling predators are largely unstudied in Africa. To assess the relative roles of large mammals, rodents, and invertebrates as predators of Acacia seedlings in an African savanna, we conducted two experiments in which we exposed Acacia drepanolobium seedlings to different guilds of herbivores. In the first experiment, seedlings exposed to rodent and invertebrate herbivores did not suffer greater damage than did seedlings exposed only to invertebrates, suggesting that invertebrates caused most of the damage to the seedlings. In the second experiment, 63% of seedlings exposed to all herbivores (large mammals, rodents, and invertebrates) suffered major damage or mortality in 14 days. Seedlings exposed to only rodents and invertebrates, however, suffered damage at a faster rate than did seedlings exposed to rodents, invertebrates, and large mammals, suggesting that small herbivores (rodents and invertebrates) might be compensating for the removal of large herbivores. Certain specific types of damage, such as cotyledon removal, were significantly more common in areas from which large mammals had been excluded, suggesting that the invertebrate herbivore community may differ between areas with and without large mammals. Overall, invertebrates caused the greatest damage to seedlings while rodents had relatively little effect and no seedlings were consumed or trampled by large mammals. Our results indicate that invertebrates can have a pronounced influence on seedling survival for a dominant savanna tree, which in turn may influence tree recruitment and ecosystem function.

Specialized DNA polymerases, cellular survival, and the genesis of mutations.

Cell death caused by arrested replication of damaged or structurally altered DNA can be avoided in prokaryotic and eukaryotic cells by multiple DNA polymerases that are specialized to bypass DNA damage. Some of these polymerases perform such translesion DNA synthesis of specific types of damage with high genetic fidelity. However, they exhibit greatly reduced fidelity when they operate on undamaged DNA or on DNA with lesions that are (apparently) not cognate substrates. The low fidelity of some of these specialized polymerases when copying undamaged DNA may be physiologically functional, including generating immunoglobulin diversity.

Homogenized constitutive equations for linear viscoelastic unidirectional composites with growing transverse cracks

Three-dimensional, thermomechanical constitutive equations and an associated correspondence principle are developed for a linear viscoelastic, unidirectional composite with growing damage. The type of damage modeled is transverse cracking, which is commonly observed in laminates consisting of unidirectional fiber layers. The equations allow for aging. First, the constitutive equations without damage are summarized. They are then modified to allow for time-dependent damage by means of a correspondence principle. This principle relates elastic and viscoelastic solutions in the time-plane; the familiar correspondence principle based on the Laplace transform is not applicable because of the aging and crack growth. Some existing, simplified micromechanical models for elastic media are extended to viscoelasticity and then used to demonstrate that the requirements of the correspondence principle are quite-well satisfied for realistic material behavior. The correspondence principle is developed in the Appendix. It generalizes a previously-developed principle for plane stress in fiber-composites to three-dimensional conditions, and is not limited to the specific type of damage covered in the body of the paper.

Presenilin-1 regulates the neuronal threshold to excitotoxicity both physiologically and pathologically.

A direct pathophysiological role of Familial Alzheimer's Disease (FAD)-associated Presenilin 1 (PS1) mutations in neuronal vulnerability remains a controversial matter. We evaluated the relationship between PS1 and excitotoxicity in four different experimental models of neurotoxicity by using primary neurons from (i) transgenic (tg) mice overexpressing a human FAD-linked PS1 variant (L286V mutation), (ii) tg mice overexpressing human wild-type (wt) PS1, (iii) PS1 knockout mice, and (iv) wt mice in which PS1 gene expression was knocked down by antisense treatment. We found that primary neurons overexpressing mutated PS1 showed an increased vulnerability to both excitotoxic and hypoxic-hypoglycemic damage when compared with neurons obtained from either mice overexpressing human wt PS1 or in wt mice. In addition, reduced excitotoxic damage was obtained in neurons in which PS1 expression was absent or diminished. Data obtained in in vivo experimental models of excitotoxicity partially supported the in vitro observations. Accelerated neuronal death was demonstrated in the hippocampus of mice overexpressing mutated PS1 after peripheral administration of kainic acid in comparison with wt animals. However, measurement of the infarct volume after middle cerebral artery occlusion did not show significant difference between the two animal groups. The results altogether suggest that expression of FAD-linked PS1 variants increases the vulnerability of neurons to a specific type of damage in which excitotoxicity plays a relevant role. In addition, they support the view that reduction of endogenous PS1 expression results in neuroprotection.

ATAXIA-TELANGIECTASIA AND THE NIJMEGEN BREAKAGE SYNDROME: Related Disorders But Genes Apart

Gene mutations provide valuable clues to cellular metabolism. In humans such insights come mainly from genetic disorders. Ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are two distinct but closely related, single gene disorders that highlight a complex junction of several signal transduction pathways. These pathways appear to control defense mechanisms against specific types of damage to cellular macromolecules, and probably regulate the processing of certain types of DNA damage or normal intermediates of DNA metabolism. A-T is characterized primarily by cerebellar degeneration, immunodeficiency, genome instability, clinical radiosensitivity, and cancer predisposition. NBS shares all these features except cerebellar deterioration. The cellular phenotypes of A-T and NBS are almost indistinguishable, however, and include chromosomal instability, radiosensitivity, and defects in cell cycle checkpoints normally induced by ionizing radiation. The recent identification of the gene responsible for A-T, ATM, has revealed its product to be a large, constitutively expressed phosphoprotein with a carboxy-terminal region similar to the catalytic domain of phosphatidylinositol 3-kinases (PI 3-kinases). ATM is a member of a family of proteins identified in various organisms, which share the PI 3-kinase domain and are involved in regulation of cell cycle progression and response to genotoxic agents. Some of these proteins, most notably the DNA-dependent protein kinase, have an associated protein kinase activity, and preliminary data indicate this activity in ATM as well. Mutations in A-T patients are null alleles that truncate or destabilize the ATM protein. Atm-deficient mice recapitulate the human phenotype with slower nervous-system degeneration. Two ATM interactors, c-Abl and p53, underscore its role in cellular responses to genotoxic stress. The complexity of ATM's structure and mode of action make it a paradigm of multifaceted signal transduction proteins involved in many physiological pathways via multiple protein-protein interactions. The as yet unknown NBS protein may be a component in an ATM-based complex, with a key role in sensing and processing specific DNA damage or intermediates and signaling their presence to the cell cycle machinery.

Agriculture, écologie et développement : Introduction

This work is based in part on the papers concerning agriculture, ecology, and development contained in this issue of the Revue Tiers-Monde. It provides an overview of changing international attitudes toward environmental damage, examines 3 specific types of damage affecting developing countries in particular, and discusses the shortcomings of existing environmental projects and the prerequisites for a lasting control over environmental damage. It has become increasingly evident that pollution and environmental damage cannot be the concern exclusively of developed countries. The 1992 UN Conference on the Environment and Development in rio de Janeiro focused most of its attention on problems evident at the planetary level such as the greenhouse effect and extinction of species. Problems resulting from the impact of harmful agricultural practices on developing country ecological environments were noted somewhat in passing. The examples of tropical deforestation, the degradation of savannahs and steppes, and cultivation of new fields on steep mountainsides demonstrate the complexity and gravity of environmental problems in developing countries. The poverty of peasants and their inability to obtain the inputs that would enable them to practice a more stable type of agriculture are important factors in the damage done. A common problem is that immediate production or consumption is favored with little regard for longterm consequences. Certain agricultural practices such as the use of cultivars selected for their high yields under optimal conditions contribute to the progressive disappearance of varieties with special properties such as resistance to disease or insects that may be needed in the future. Excessive use of herbicides, pesticides, or fertilizer may bring problems of pollution and toxicity. Numerous development projects sponsored by donors from the developed countries have been designed to pursue short term objectives with insufficient attention to longterm damage. Environmental protection projects have frequently fallen short of their goals because the local populations were not consulted or involved. Some used materials such as tree species that were not adapted to local conditions or that did not meet the needs of the people. The sponsors of development projects may not be sufficiently aware of the difficulty of assuring day-to-day survival for some groups, who find the constraints imposed by the projects to be extremely burdensome. The author argues that peasants are always interested in reconciling their production objectives with protection of resources, and they are quite well informed of how to do so. Governments should ease their access to credit or the inputs that would enable them to practice a more productive agriculture with less environmental damage. A more equitable world economic order will be required before environmental protection can be assured in the poorest countries.

DNA damage and repair in brain: relationship to aging.

The usefulness of conducting DNA damage and repair studies in a postmitotic tissue like brain is emphasized. We review studies that use brain as a tissue to test the validity of the DNA damage and repair hypothesis of aging. As far as the accumulation of age dependent DNA damage is concerned, the data appear to overwhelmingly support the hypothesis. However, attempts to demonstrate a decline in DNA repair capacity as a function of age are conflicting and equally divided. Possible reasons for this discrepancy are discussed. It is suggested that assessment of the repair capacity of neurons with respect to a specific type of damage in a specific gene might yield more definitive answers regarding the role of DNA repair potential in the aging process and as a longevity assurance system.

Local correction of mod( k) lists

A mod( k) list is a robust double-linked list in which each back pointer has been modified so that it addresses the kth previous node. This paper presents a new algorithm for performing local correction in a mod( k > 3) list. Given the assumption that at most two errors are encountered during any single correction step, this algorithm performs correction whenever possible, and otherwise reports failure. The algorithm generally reports failure only if both pointers addressing a specific node have been damaged, causing this node to become disconnected. However, in a mod(3) structure one specific type of damage that causes disconnection is indistinguishable from alternative damage that does not. This also causes the algorithm to report failure.

Local correction of helix(k) lists

A helix (k) list is a robust multiply linked list having k pointers in each node. In general, the ith pointer in each node addresses the ith previous node. However, the first pointer in each node addresses the next node, rather than the previous. An algorithm for performing local correction in a helix (k>or=3) list is presented. Given the assumption that at most k errors are encountered during any single correction step, this algorithm performs correction whenever possible, and otherwise reports failure. The algorithm generally reports failure only if all k pointers addressing a specific node are damaged, causing this node to become disconnected. However, in a helix (k=3) structure, one specific type of damage that causes disconnection is indistinguishable from alternative damage that does not. This also causes the algorithm to report failure. >

Synaptonemal complex damage induced by clastogenic and anti-mitotic chemicals: implications for non-disjunction and aneuploidy

Mice were treated with mitomycin C, cyclophosphamide, amsacrine, colchicine, or vinblastine sulfate, and meiotic prophase cells analyzed for synaptonemal complex (SC) damage. All test agents caused synaptonemal complex breakage and synapsis irregularities, although propensities for inducing specific types of damage at S-phase or prophase stages varied among the chemicals. The data indicate that SC analysis can reveal chemical-spacific alterations to meitic homologue pairing/synapsis which have not generally been recognized, and which theoretically may be implicated in non-disjunction.

Comparison of the effect of polymethylmethacrylate and silicone intraocular lenses on rabbit corneal endothelium in vitro

An in vitro comparison of corneal endothelial damage caused by polymethylmethacrylate and by silicone intraocular lenses was made. Endothelial damage was assessed by vital staining of corneal endo thelium immediately following direct contact with an intraocular lens. Silicone lenses produced less damage than polymethylmethacrylate lenses. The difference could be attributed to a specific type of damage—membrane stripping—seen only after contact with poly methylmethacrylate lenses.

Effects of separate and combined treatments with gamma radiation and diethylnitrosamine in neonatal rats on the induction of altered hepatocyte foci and hepatic tumors.

To characterize the effects of combined treatments with gamma radiation and diethylnitrosamine (DEN) on the induction of histochemically detectable altered hepatocyte foci and hepatic tumors, we assessed the yields of these lesions in the livers of 150-day-old rats that had been treated neonatally with a single dose of gamma radiation (75 rad, whole body) and i.p.-injected DEN (0.15 mumol/g body wt), either separately or in combination. The combined treatments involved the administration of the two stimuli in both possible sequences, with the interval between treatments set at 1 h. The focus population was examined for two histochemical markers (elevated gamma-glutamyl transpeptidase [GGT(+)] and iron exclusion [FE(-)], giving rise to three detectable focus phenotypes, i.e. GGT(+) foci, FE(-) foci, and GGT(+), FE(-) foci. Frequencies of the three phenotypes were quantitated through the use of serial frozen sectioning techniques and computer-assisted image analysis. GGT(+) focus induction was synergistically enhanced by the combined treatment irrespective of the order in which the two stimuli were administered; the remaining two phenotypes did not show such enhancement. The magnitude of the GGT(+) focus response was significantly greater when the treatment sequence was gamma----DEN as opposed to DEN----gamma. Tumor yields in rats receiving combined gamma--DEN treatment were similar to those in rats receiving the DEN alone, irrespective of the gamma--DEN treatment sequence. These results suggest that phenotypically distinguishable lesions, including foci with different histochemical marker patterns and tumors, originate from specific types of damage at different genetic loci and are developmentally independent; and the expression of the GGT(+) marker per se in altered hepatocyte foci is not a reliable index of incipient hepatic neoplasia.

Damage and Failure at Elevated Temperature

Damage of a material is a process by which the strength and ductility are degraded. Failure of a component is the inability to perform a function within the design specifications and imposed limits. An index of failure is defined as a limit on a specific type of damage. This paper describes the flow and fracture characteristics of metals in a high temperature environment and relates these characteristics to the accumulation of damage.

Mature DNA from temperate bacillusphage phi105 requires primary recombination to be infectious in transfection.

When infectivity of mature DNA from phage φ105 is measured as a function of DNA concentration a curve with a slope greater than one is obtained, whereas marker rescue from mature DNA or infectivity of prophage DNA give a slope of one. In mixed transfection with two genetically marked mature DNA preparations the frequency of cells yielding wild type recombinants is independent of DNA concentration. When the same type of experiment is performed with prophage DNA a dependence of recombinant formation on DNA concentration is seen. The rate of formation of infectious centers is constant per unit time for prophage DNA but increases with increasing time of contact between competent cells and DNA in mature DNA. Half molecules of mature DNA are inhibitory to transfection with either prophage or mature DNA. Recombinant formation between whole and half molecules of mature DNA is concentration dependent. The results show that (primary) recombination is needed to yield an infectious center in transfection with mature φ105 DNA. It is suggested that this need arises due to a specific type of damage to the mature DNA molecule as it is taken up by the competent cell.

Correlation of Irradiation Data Using Activation Fluences and Irradiation Temperature

A new method of correlating radiation damage data is tested using actual measured data taken from the open literature. This method, the activation fluence method, was found to be as accurate as other contemporary models with which it was compared. The new method also has several advantages over the other methods. The method employs a new entity, the activation fluence (time-integrated specific activation rate), as the independent variables in a regression model. Temperature at which the irradiation takes place is also a variable. Although the method was tested for a specific type of damage (change in nil-ductility transition temperature for A302-B steel) it has no inherent restrictions and is limited only by the imagination of the user.