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Signalling DNA Damage (Book chapter)

Authors: ---
ISBN: 9789535107378 Year: DOI: 10.5772/50863 Language: English
Publisher: IntechOpen Grant: FP7 Ideas: European Research Council - 210520
Subject: Science (General)
Added to DOAB on : 2019-01-17 11:47:57
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During our lifetime, the genome is constantly being exposed to different types of damage caused either by exogenous sources (radiations and/or genotoxic compound) but also as byproducts of endogenous processes (reactive oxigen species during respiration, stalled forks during replication, eroded telomeres, etc). From a structural point of view, there are many types of DNA damage including single or double strand breaks, base modifications and losses or base-pair mismatches. The amount of lesions that we face is enormous with estimates suggesting that each of our 1013 cells has to deal with around 10.000 lesions per day [1]. While the majority of these events are properly resolved by specialized mechanisms, a deficient response to DNA damage, and particularly to DSB, harbors a serious threat to human health [2].&#xD;&#xD;DSB can be formed [1] following an exposure to ionizing radiation (X- or γ-rays) or clastogenic drugs; [2] endogenously, during DNA replication, or [3], as a consequence of reactive oxygen species (ROS) generated during oxidative metabolism. In addition, programmed DSB are used as repair intermediates during V(D)J and Class-Switch recombination (CSR) in lymphocytes [3], or during meiotic recombination [4]. Because of this, immunodeficiency and/or sterility problems are frequently associated with DDR-related pathologies.

Keywords

dna damage

Evènements climatiques extrêmes

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ISBN: 9782759805082 Year: Pages: 240 DOI: 10.26530/OAPEN_519668 Language: French
Publisher: EDP SCIENCES
Subject: General and Civil Engineering
Added to DOAB on : 2014-07-31 09:10:11
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Abstract

Climate events, storms, damage

Keywords

damage --- storms --- climate events

High Cycle Fatigue of Al and Cu Thin Films by a Novel High-Throughput Method

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Book Series: Schriftenreihe des Instituts für Angewandte Materialien, Karlsruher Institut für Technologie ISSN: 21929963 ISBN: 9783731500254 Year: Volume: 23 Pages: XII, 140 p. DOI: 10.5445/KSP/1000034759 Language: ENGLISH
Publisher: KIT Scientific Publishing
Subject: Technology (General)
Added to DOAB on : 2019-07-30 20:02:01
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In the last two decades, the reliability of small electronic devices used in automotive or consumer electronics gained researchers attention. Thus, there is the need to understand the fatigue properties and damage mechanisms of thin films. In this thesis a novel high-throughput testing method for thin films on Si substrate is presented. The specialty of this method is to test one sample at different strain amplitudes at the same time and measure an entire lifetime curve with only one experiment.

Neuronal mechanisms of epileptogenesis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193820 Year: Pages: 223 DOI: 10.3389/978-2-88919-382-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-03 13:02:24
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Several types of brain injuries are causes of acquired temporal lobe epilepsy (TLE). The seizure-free "latent period" that often follows the brain injury is of unknown mechanistic significance but is commonly considered as the "epileptogenic" period characterized by gradual pathogenic processes leading to the onset of clinically detectable epilepsy. Acute convulsive status epilepticus (SE) is often associated with an adverse developmental outcome characterized by learning disabilities related to the cumulative effects of seizures and development of TLE. The symptomatic manifestations of TLE appear only after a widespread irreversible damage of entorhinal cortex, and hippocampus, the brain area most affected by this disease. These pathological features of TLE reduce the possibility of successful therapeutic approaches, often rendering the disease refractory. The difficult clinical management of chronic TLE and the limited success rate of surgical approaches, increase the incapacitating nature of this specific epileptic disorder. Prevention of TLE with an appropriate intervention after a known inciting event (in the case of acquired epilepsy) might represent the most ambitious goal in the clinical treatment of this epileptic disorder, but has been largely unsuccessful to this point. Clinical trials aimed at prevention of chronic epilepsy have often produced negative, disappointing results. However, in most cases, these studies ultimately evaluated the downstream clinical manifestations, failing to monitor early, specific molecular epileptogenic events. Therefore, elucidation of the underlying mechanisms of epileptogenesis, and their time course(s) are essential. The primary purpose of this topic is to collect scientific contributions providing novel insights in the cellular and molecular mechanisms of epileptogenesis as potential targets for innovative therapeutic approaches aimed at preventing the chronic epileptic disorder.

Grappling with the Multifaceted World of the DNA Damage Response

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450572 Year: Pages: 306 DOI: 10.3389/978-2-88945-057-2 Language: English
Publisher: Frontiers Media SA
Subject: Genetics --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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DNA damage is a major threat to genomic integrity and cell survival. It can arise both spontaneously and in response to exogenous agents. DNA damage can attack most parts of the DNA structure, ranging from minor and major chemical modifications, to single-strand breaks (SSBs) and gaps, to full double-strand breaks (DSBs). If DNA injuries are mis-repaired or unrepaired, they may ultimately result in mutations or wider-scale genome aberrations that threaten cell homeostasis. Consequently, the cells elicit an elaborate signalling network, known as DNA damage response (DDR), to detect and repair these cytotoxic lesions. This Research Topic was aimed at comprehensive investigations of basic and novel mechanisms that underlie the DNA damage response in eukaryotes.DNA damage is a major threat to genomic integrity and cell survival. It can arise both spontaneously and in response to exogenous agents. DNA damage can attack most parts of the DNA structure, ranging from minor and major chemical modifications, to single-strand breaks (SSBs) and gaps, to full double-strand breaks (DSBs). If DNA injuries are mis-repaired or unrepaired, they may ultimately result in mutations or wider-scale genome aberrations that threaten cell homeostasis. Consequently, the cells elicit an elaborate signalling network, known as DNA damage response (DDR), to detect and repair these cytotoxic lesions. This Research Topic was aimed at comprehensive investigations of basic and novel mechanisms that underlie the DNA damage response in eukaryotes.

11 Análisis numérico de la reparación y refuerzo de estructuras con FRP (Book chapter)

Authors: --- --- --- --- et al.
ISBN: 978849417292 Year: Pages: 31 Language: Spanish;
Publisher: OmniaScience Grant: FP7 Ideas: European Research Council - 320815
Subject: Architecture
Added to DOAB on : 2019-01-17 11:45:55
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This chapter presents a procedure to assess the magnitude of the damage local and global damage in structures subjected to static and dynamic actions, with special&#xD;emphasis on the seismic problem. In addition to the formulation for the evaluation of the damage,&#xD;introduces the concept of structural reinforcement and repair by composite laminates&#xD;of epoxy matrix with carbon fiber reinforcement. For this purpose, the&#xD;use of the theory of mixtures to compose a composite material from their&#xD;basic components. Damage is also assessed in these reinforced and / or repaired structures&#xD;and the influence of these improvements on the assessment of the overall damage of the structure is discussed.

Schmerzengeld für Schock- und Trauerschäden

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ISBN: 9783205781998 Year: Pages: 262 Seiten DOI: 10.26530/oapen_437173 Language: German
Publisher: Böhlau Grant: Austrian Science Fund - D 3991
Subject: Law
Added to DOAB on : 2013-03-27 11:49:11
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The doctoral thesis is a comparing study of the Austrian, German, Swiss, England and French tort law,&#xD;also contains the Principles of the European Group of tort law and handle four major questions:&#xD;(1) Who are the close relatives?&#xD;(2) What is the difference between close relatives and other people who suffer a damage because of the&#xD;harm of another person?&#xD;(3) Is it possible that the tortfeasor hold the fault of the victime against the close relatives who suffer&#xD;nervous shock or bereavement?&#xD;(4) Do the close relatives have a right to claim for damage on their own or is that related to the claim&#xD;of the victime?

Ubiquitin and Ubiquitin-Relative SUMO in DNA Damage Response

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454419 Year: Pages: 183 DOI: 10.3389/978-2-88945-441-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
Added to DOAB on : 2018-11-16 17:17:57
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DNA damage response (DDR) is a term that includes a variety of highly sophisticated mechanisms that cells have evolved in safeguarding the genome from the deleterious consequences of DNA damage. It is estimated that every single cell receives tens of thousands of DNA lesions per day. Failure of DDR to properly respond to DNA damage leads to stem cell dysfunction, accelerated ageing, various degenerative diseases or cancer. The sole function of DDR is to recognize diverse DNA lesions, signal their presence, activate cell cycle arrest and finally recruit specific DNA repair proteins to fix the DNA damage and thus prevent genomic instability. DDR is composed of hundreds of spatiotemporally regulated and interconnected proteins, which are able to promptly respond to various DNA lesions. So it is not surprising that mutations in genes encoding various DDR proteins cause embryonic lethality, malignancies, neurodegenerative diseases and premature ageing. The importance of DDR for cell survival and genome stability is unquestionable, but how the sophisticated network of hundreds of different DDR proteins is spatiotemporally coordinated is far from being understood. In the last ten years ubiquitin (ubiquitination) and the ubiquitin-relative SUMO (sumoylation) have emerged as essential posttranslational modifications that regulate DDR. Beside a plethora of ubiqutin and sumo E1-activating enzymes, E2-conjugating enzymes, E3-ligases and ubiquitin/sumo proteases involved in ubiquitination and sumoylation, the complexity of ubiqutin and sumo systems is additionally increased by the fact that both ubiquitin and sumo can form a variety of different chains on substrates which govern the substrate fate, such as its interaction with other proteins, changing its enzymatic activity or promoting substrate degradation. The importance of ubiquitin/SUMO systems in the orchestration of DDR is best illustrated in patients with mutations in E3-ubiquitin ligases BRCA1 or RNF168. BRCA1 is essential for proper function of DDR and its mutations lead to triple-negative breast and ovarian cancers. RNF168 is an E3 ubiquitin ligase, which creates the ubiquitin docking platform for recruitment of different DNA damage signalling and repair proteins at sites of DNA lesion, and its mutations cause RIDDLE syndrome characterized by radiosensitivity, immunodeficiency and learning disability. In addition, recently discovered the ubiquitin receptor protein SPRTN is part of the DNA replication machinery and its mutations cause early-onset hepatocellular carcinoma and premature ageing in humans. Despite more than 700 different enzymes directly involved in ubiquitination and sumoylation processes only few of them are known to play a role in DDR. Therefore, we feel that the role of ubiquitin and the ubiquitin-related SUMO in DDR is far from being understood, and that this is the emerging field that will hugely expand in the next decade due to the rapid development of a new generation of technologies, which will allow us a more robust and precise analyses of human genome, transcriptome and proteome. In this Research Topic we provide a comprehensive overview of our current understanding of ubiquitin and SUMO pathways in all aspects of DDR, from DNA replication to different DNA repair pathways, and demonstrate how alterations in these pathways cause genomic instability that is linked to degenerative diseases, cancer and pathological ageing.

Nexo de causalidade e estado anterior na avaliação médico-legal do dano corporal

Authors: --- ---
Book Series: Ciências da Saúde ISBN: 9789892611433 Year: Pages: 173 DOI: https://doi.org/10.14195/978-989-26-1144-0 Language: Portuguese
Publisher: Coimbra University Press
Subject: Medicine (General)
Added to DOAB on : 2019-04-23 16:21:06
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This work contributes to a better characterization, in forensic perspective, of the assessment of post-traumatic bodily injury when a prior state is present and promotes the uniformity increasing of the assessment carried out by professionals on the concepts analyzed. Will be addressed the possible associations between organic or traumatic pathologies and a previous state, in arder to better describe the general and specific principies for the establishment .of imputability and/or aggravation of those pathologic conditions. In that regard, will be narrated medicolegal expertise where traumatic injuries caused any further deterioration of the previous state or that this negatively influenced the trauma consequences. Such cases were analyzed, emphasizing the methodology of forensic evaluation and the form of appreciation of the prior state. The aim is to also understand what the effect of forensic conclusion in the court ruling, which concludes this work with an analysis of value or influence of forensic assessment in taking judicial decision in Portugal when a pre-existing pathological condition was present, identifying the strengths and weaknesses of it.

Structural Health Monitoring (SHM) of Civil Structures

Authors: --- ---
ISBN: 9783038427834 9783038427841 Year: Pages: X, 490 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: General and Civil Engineering
Added to DOAB on : 2018-04-20 14:47:20
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At the current time of writing, the American Society of Civil Engineers (ASCE) has awarded American infrastructure a grade of D+, meaning poor and at risk. Part of the reason for the low grade is due to the rapid deterioration of structural integrity and the inability of most places to safely meet future demands. Deficiencies in these areas may be remediated by advancements in structural health monitoring (SHM) technologies that provide sensing systems to automatically and economically diagnose structural integrity. In a sense, SHM technologies will help pave the way to intelligent structures that are able to detect damage by themselves and even warn occupants of any danger due to impending structural failure. Engineering sensors and developing smart algorithms for SHM often involves the close collaboration of a surprisingly large breadth of specialties. In this book, we have collected a thin but representative slice of the most recent research in SHM, and hope that the reader will gain an inspiring view of today’s research landscape and a notion of what is to come.

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