This paper is directed towards a new concept of structural integrity, including a novel and forward-looking approach, and broadening the amplitude of the definition, thereby offering a multi-scale ...analysis comprising and covering all length scales in the theoretical framework of the new terms of giga-, mega-, macro-, micro- and nano-structural integrity, and therefore the science of fracture mechanics & structural integrity can be seen as a branch of material science & engineering, and the novel idea of material integrity can also be discussed. In addition, the concept of structural integrity is extended to fields such as the biology, or to the case of non-material structures, as well as to the area of human behaviour and psychology, developing the concept of personal structural integrity (or, simply, personal integrity). The paper represents also a heartfelt tribute to the artist and engineer Leonardo da Vinci, as well as to the physicist and mathematician Galileo Galilei for their pioneering works in the fields of material strength, fracture and structural integrity.
Abstract
Expansion of simple DNA repeats is responsible for numerous hereditary diseases in humans. The role of DNA replication, repair and transcription in the expansion process has been well ...documented. Here we analyzed, in a yeast experimental system, the role of RNA-DNA hybrids in genetic instability of long (GAA)n repeats, which cause Friedreich's ataxia. Knocking out both yeast RNase H enzymes, which counteract the formation of RNA-DNA hybrids, increased (GAA)n repeat expansion and contraction rates when the repetitive sequence was transcribed. Unexpectedly, we observed a similar increase in repeat instability in RNase H-deficient cells when we either changed the direction of transcription-replication collisions, or flipped the repeat sequence such that the (UUC)n run occurred in the transcript. The increase in repeat expansions in RNase H-deficient strains was dependent on Rad52 and Pol32 proteins, suggesting that break-induced replication (BIR) is responsible for this effect. We conclude that expansions of (GAA)n repeats are induced by the formation of RNA-DNA hybrids that trigger BIR. Since this stimulation is independent of which strand of the repeat (homopurine or homopyrimidine) is in the RNA transcript, we hypothesize that triplex H-DNA structures stabilized by an RNA-DNA hybrid (H-loops), rather than conventional R-loops, could be responsible.
RAD51 filament is crucial for the homology-dependent repair of DNA double-strand breaks and stalled DNA replication fork protection. Positive and negative regulators control RAD51 filament assembly ...and disassembly. RAD51 is vital for genome integrity but excessive accumulation of RAD51 on chromatin causes genome instability and growth defects. However, the detailed mechanism underlying RAD51 disassembly by negative regulators and the physiological consequence of abnormal RAD51 persistence remain largely unknown. Here, we report the role of the human AAA+ ATPase FIGNL1 in suppressing a novel type of RAD51-mediated genome instability. FIGNL1 knockout human cells were defective in RAD51 dissociation after replication fork restart and accumulated ultra-fine chromosome bridges (UFBs), whose formation depends on RAD51 rather than replication fork stalling. FIGNL1 suppresses homologous recombination intermediate-like UFBs generated between sister chromatids at genomic loci with repeated sequences such as telomeres and centromeres. These data suggest that RAD51 persistence per se induces the formation of unresolved linkage between sister chromatids resulting in catastrophic genome instability. FIGNL1 facilitates post-replicative disassembly of RAD51 filament to suppress abnormal recombination intermediates and UFBs. These findings implicate FIGNL1 as a key factor required for active RAD51 removal after processing of stalled replication forks, which is essential to maintain genome stability.
This paper develops other by the author on a novel and forward-looking approach to the concept of structural integrity, comprising and covering all length scales in the theoretical framework of the ...innovative terms of giga-, mega-, macro-, micro- and nano-structural integrity, and thus the science of fracture mechanics & structural integrity can be seen as a branch of material science & engineering, and the novel idea of material integrity can also be discussed. In addition, the concept of structural integrity is extended to fields such as the biology, or to the case of non-material structures. The paper is also a tribute to the physicists Galileo Galilei who can be considered as the father of fracture mechanics.
Remote data integrity checking is of great importance to the security of cloud-based information systems. Previous works generally assume a trusted third party to oversee the integrity of the ...outsourced data, which may be invalid in practice. In this paper, we utilize the blockchain to construct a novel privacy-preserving remote data integrity checking scheme for Internet of Things (IoT) information management systems without involving trusted third parties. Our scheme leverages the Lifted EC-ElGamal cryptosystem, bilinear pairing, and blockchain to support efficient public batch signature verifications and protect the security and data privacy of the IoT systems. The results of the experiment demonstrate the efficiency of our scheme.
Abstract
Melanin protects skin cells from ultraviolet radiation-induced DNA damage. However, intermediates of eumelanin are highly reactive quinones that are potentially genotoxic. In this study, we ...systematically investigate the effect of sustained elevation of melanogenesis and map the consequent cellular repair response of melanocytes. Pigmentation increases γH2AX foci, DNA abasic sites, causes replication stress and invokes translesion polymerase Polκ in primary human melanocytes, as well as mouse melanoma cells. Confirming the causal link, CRISPR-based genetic ablation of tyrosinase results in depigmented cells with low Polκ levels. During pigmentation, Polκ activates replication stress response and keeps a check on uncontrolled proliferation of cells harboring melanin-damaged DNA. The mutational landscape observed in human melanoma could in part explain the error-prone bypass of DNA lesions by Polκ, whose absence would lead to genome instability. Thereby, translesion polymerase Polκ is a critical response of pigmenting melanocytes to combat melanin-induced DNA alterations. Our study illuminates the dark side of melanin and identifies (eu)melanogenesis as a key missing link between tanning response and mutagenesis, mediated via the necessary evil translesion polymerase, Polκ.
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Graphical Abstract
Abstract
Using human embryonic, adult and cancer stem cells/stem cell-like cells (SCs), we demonstrate that DNA replication speed differs in SCs and their differentiated counterparts. While SCs ...decelerate DNA replication, differentiated cells synthesize DNA faster and accumulate DNA damage. Notably, both replication phenotypes depend on p53 and polymerase iota (POLι). By exploring protein interactions and newly synthesized DNA, we show that SCs promote complex formation of p53 and POLι at replication sites. Intriguingly, in SCs the translocase ZRANB3 is recruited to POLι and required for slow-down of DNA replication. The known role of ZRANB3 in fork reversal suggests that the p53–POLι complex mediates slow but safe bypass of replication barriers in SCs. In differentiated cells, POLι localizes more transiently to sites of DNA synthesis and no longer interacts with p53 facilitating fast POLι-dependent DNA replication. In this alternative scenario, POLι associates with the p53 target p21, which antagonizes PCNA poly-ubiquitination and, thereby potentially disfavors the recruitment of translocases. Altogether, we provide evidence for diametrically opposed DNA replication phenotypes in SCs and their differentiated counterparts putting DNA replication-based strategies in the spotlight for the creation of therapeutic opportunities targeting SCs.
With cloud storage services, users can remotely store their data to the cloud and realize the data sharing with others. Remote data integrity auditing is proposed to guarantee the integrity of the ...data stored in the cloud. In some common cloud storage systems such as the electronic health records system, the cloud file might contain some sensitive information. The sensitive information should not be exposed to others when the cloud file is shared. Encrypting the whole shared file can realize the sensitive information hiding, but will make this shared file unable to be used by others. How to realize data sharing with sensitive information hiding in remote data integrity auditing still has not been explored up to now. In order to address this problem, we propose a remote data integrity auditing scheme that realizes data sharing with sensitive information hiding in this paper. In this scheme, a sanitizer is used to sanitize the data blocks corresponding to the sensitive information of the file and transforms these data blocks' signatures into valid ones for the sanitized file. These signatures are used to verify the integrity of the sanitized file in the phase of integrity auditing. As a result, our scheme makes the file stored in the cloud able to be shared and used by others on the condition that the sensitive information is hidden, while the remote data integrity auditing is still able to be efficiently executed. Meanwhile, the proposed scheme is based on identity-based cryptography, which simplifies the complicated certificate management. The security analysis and the performance evaluation show that the proposed scheme is secure and efficient.
•We propose a blockchain-based fish farm platform to guarantee agriculture data integrity.•We make the use of smart contract to automate the data processing in the fish farm.•We implement a proof of ...concept that integrates a legacy smart fish farm system with the Hyperledger Fabric.
Internet of Things (IoT) has opened up a new dimension for smart farming and agriculture because of the natural feature that makes it possible to assign tasks made by a user or that transfers agriculture data obtained through sensors to producers for analysis on various terminal devices. In recent years, heightened interest in agriculture data has arisen since the commercialization of precision agriculture technology. Agriculture data are known to be messy, especially from combine yield monitors, and analysts are concerned with the validity of data, especially given that other people may have impacted data quality at various steps along the data path. The blockchain can be a possible solution to the analyst’s problem of uncertain data quality from prior data manipulation since it ensures data have not been inappropriately manipulated or at the very least documents what changes have been made by specific individuals. This paper proposes a blockchain-based fish farm platform to ensure agriculture data integrity. The designed platform aims to provide fish farmers with secure storage for preserving the large amounts of agriculture data that cannot be tampered with. Diverse processes of the fish farm are executed automatically by using the smart contract to reduce the risk of error or manipulation. A proof of concept that integrates a legacy fish farm system with the Hyperledger Fabric blockchain is implemented on top of the proposed architecture. The efficiency and usability of the proposed platform are demonstrated through a series of experiments using various metrics.
Thematic analysis (TA) is widely used in qualitative psychology. In using TA, researchers must choose between a diverse range of approaches that can differ considerably in their underlying (but often ...implicit) conceptualizations of qualitative research, meaningful knowledge production, and key constructs such as themes, as well as analytic procedures. This diversity within the method of TA is typically poorly understood and rarely acknowledged, resulting in the frequent publication of research lacking in design coherence. Furthermore, because TA offers researchers something closer to a method (a transtheoretical tool or technique) rather than a methodology (a theoretically informed framework for research), one with considerable theoretical and design flexibility, researchers need to engage in careful conceptual and design thinking to produce TA research with methodological integrity. In this article, we support researchers in their conceptual and design thinking for TA, and particularly for the reflexive approach we have developed, by guiding them through the conceptual underpinnings of different approaches to TA, and key design considerations. We outline our typology of three main "schools" of TA-coding reliability, codebook, and reflexive-and consider how these differ in their conceptual underpinnings, with a particular focus on the distinct characteristics of our reflexive approach. We discuss key areas of design-research questions, data collection, participant/data item selection strategy and criteria, ethics, and quality standards and practices-and end with guidance on reporting standards for reflexive TA.
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