18 results on '"MMS"'
Search Results
2. Tracking and evaluation method focusing on continuity of power line based on three-dimensional point cloud data
- Author
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Shota Takagi and Jun-ya Takayama
- Subjects
Three-dimensional point cloud data ,MMS ,Power line detection ,Electric apparatus and materials. Electric circuits. Electric networks ,TK452-454.4 - Abstract
Poles and overhead power lines have been common, and maintaining them is necessary. Increasingly, mobile mapping system (MMS) based on integration of various positioning, navigation and imaging data collection sensors is used to maintain the complex structure of power lines. However, MMS algorithms are still a work in progress and most limit measurement environments. Therefore, our purpose is to develop an evaluation method that can handle various challenging scenarios such as complicated configurations, ground slopes on a real world scale.In this paper, we propose a new algorithm for performing efficient extraction and tracking of powerlines from a three-dimensional point cloud data. Our algorithm focuses on the continuity of power lines, and three characteristic properties are used in the algorithm process: Dense point cloud, small color difference, and small light-intensity difference. Experimental results show that proposed method which focuses on the continuity of power lines is effective.
- Published
- 2021
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3. Chemical composition, genotoxicity and antigenotoxicity study of Artemisia herba-alba using the eye and wing SMART assay of Drosophila melanogaster
- Author
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Sanae Amkiss, Abdelkrim Dalouh, and Mohamed Idaomar
- Subjects
Artemisia herba-alba ,GS-MS ,SMART Assays ,Antigenotoxicity ,MMS ,Chemistry ,QD1-999 - Abstract
The purpose of this study was to determine the chemical composition and to evaluate the genotoxic and antigentoxic activites of the Moroccan Artemisia herba-alba ethanolic extract. The ethanolic extract of Artemisia herba-alba was analyzed by gas chromatography coupled with mass spectroscopy (GC-MS). The mutagenic and antimutagenic activities were evaluated using the somatic mutation and recombination test (SMART) on Drosophila melanogaster. Methyl methanesulfonate (MMS) was used as the positive control.Twenty-one compounds of the Artemisia herba-alba ethanol extract were identified; the main monoterpenes identified are camphor, α-thujone and β-thujone. Ethanolic extract of Artemisia herba-alba did not show gentotoxicity at doses used in SMART Assays. In the co-treatment, a dose-dependent decrease in mutation frequency was observed for this plant. Ethanolic extract of Artemisia herba-alba at 1.5% demonstrated a marked decrease in MMS with a strong inhibitory effect (80%). The results demonstrate that the Artemisia herba-alba exerted a significant and potent anti-mutagenic activity in wing and eye-spot of D. melanogaster.
- Published
- 2021
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- View/download PDF
4. The development of a mining method selection model through a detailed assessment of multi-criteria decision methods
- Author
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V.D. Baloyi and L.D. Meyer
- Subjects
MCDM ,MMSM ,MMS ,Factors ,Mining methods ,Technology - Abstract
In the past decades, attempts were made to build a systematic approach to mining method selection (MMS) Ooriad et al., [1]. This is because MMS is a complex and irreversible process. Since it can affect the economic potential of a project, the approach must be as thorough, precise, and accurate as possible. The key challenges of the previously established techniques such as the Nicholas and Laubscher method are that, there was a lack of engineering judgement in the process of selecting a mining method. In other instances, not all the parameters required in the mining method selection process were considered; i.e. economics would be the basis of the final decision of a mining method without taking into consideration other factors such as geology [2]. While other techniques just considered a few parameters and a limited number of mining methods as alternatives (Namin, 2008). Some techniques were customised procedures for a specific orebody [3]. Each orebody is unique; therefore, the approach of just adopting the same mining method for similar commodities was not always an effective or realistic approach Therefore, the existing procedures were found to be inadequate and not applicable for consideration in all MMS processes.To solve the challenges stated above, an up-to-date approach to MMS is the use of multi-criteria decision-making (MCDM) tools to aid in the process. The MCDM are effective in facilitating a decision-making process; however, the use of MCDM has not gained enough popularity across countries and in the mining industry especially in MMS [4]. Their successful implementation in other industries such as in manufacturing companies, water management, quality control, transportation, and product design [5] present an opportunity for further exploration in MMS. In this research, these MCDMs were further explored as starting point to solving the challenge faced in MMS.With the aim of developing a systematic and an unbiased approach that caters for subjective and objective analysis in MMS, this study investigated 10 MCDMs- TOPSIS, TODIM, VIKOR, GRA, PROMETHEE, OCRA, ARAS, COPRAS, SAW, and CP with potential to solve the MMS challenge. The study focused on deriving a model where the MCDMs can be integrated and be successfully used for MMS. Included in the research are factors and mining methods that are necessary in MMS. The aim was to use the factors and mining methods as inputs to the developed MMSM.In the result section, case studies were used to analyse the MCDMs following a descriptive and a statistical analysis (sensitivity analysis, spearman correlation, and Kendall’s coefficient.). PROMETHEE, TOPSIS, and TODIM stood out as methods for use in the selection of mining method in the coal mining industry. From the research findings, it was generally concluded that OCRA, ARAS, CP, SAW, and COPRAS are simplified approaches of the afore-mentioned methods. VIKOR’s rankings were outlying and the conclusion was that it was not a suitable method for MMS. GRA’s conclusion based on the literature view was that there remain many unanswered questions about its mathematical foundations.The MMSM was developed using the results obtained. In the MMSM, first, the user defines the problem. The approach is of case-based reasoning (CBR); where the user can retrieve, re-use, revise and then retain the information (in the database) for future use. The user can always search within the database for a similar problem to select a MCDM, factors and methods; and this may be one of the future areas of improvement on the developed MMSM because there are a number of factors, MCDMs, and mining methods that the user may need to go through before getting to the relevant MCDM. One of the recommendations made by the author was that the user must understand the theoretical background of the MCDM before using it in the MMSM. In future studies, algorithms for selection of a suitable MCDM in the MMSM can be developed so that once the problem has been defined and structured; the user may not struggle with knowing which method to use amongst the suggested. Also, an application-based approach may be investigated further.
- Published
- 2020
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5. Chemical composition, genotoxicity and antigenotoxicity study of Artemisia herba-alba using the eye and wing SMART assay of Drosophila melanogaster
- Author
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Mohamed Idaomar, Abdelkrim Dalouh, and Sanae Amkiss
- Subjects
GS-MS ,General Chemical Engineering ,02 engineering and technology ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,lcsh:Chemistry ,chemistry.chemical_compound ,Camphor ,medicine ,Melanogaster ,Mutation frequency ,Artemisia herba-alba ,biology ,Traditional medicine ,Chemistry ,food and beverages ,General Chemistry ,Antigenotoxicity ,021001 nanoscience & nanotechnology ,biology.organism_classification ,MMS ,0104 chemical sciences ,Methyl methanesulfonate ,lcsh:QD1-999 ,Artemisia ,Drosophila melanogaster ,0210 nano-technology ,Genotoxicity ,SMART Assays - Abstract
The purpose of this study was to determine the chemical composition and to evaluate the genotoxic and antigentoxic activites of the Moroccan Artemisia herba-alba ethanolic extract. The ethanolic extract of Artemisia herba-alba was analyzed by gas chromatography coupled with mass spectroscopy (GC-MS). The mutagenic and antimutagenic activities were evaluated using the somatic mutation and recombination test (SMART) on Drosophila melanogaster. Methyl methanesulfonate (MMS) was used as the positive control. Twenty-one compounds of the Artemisia herba-alba ethanol extract were identified; the main monoterpenes identified are camphor, α-thujone and β-thujone. Ethanolic extract of Artemisia herba-alba did not show gentotoxicity at doses used in SMART Assays. In the co-treatment, a dose-dependent decrease in mutation frequency was observed for this plant. Ethanolic extract of Artemisia herba-alba at 1.5% demonstrated a marked decrease in MMS with a strong inhibitory effect (80%). The results demonstrate that the Artemisia herba-alba exerted a significant and potent anti-mutagenic activity in wing and eye-spot of D. melanogaster.
- Published
- 2021
6. Mohs micrographic surgery revisited: A multidisciplinary, collaborative approach for the treatment of aggressive and recurrent basal cell carcinoma on the head and neck.
- Author
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Aristokleous I, Schultz I, Vassilaki I, Krynitz B, Lapins J, Girnita A, and Nilsson MF
- Subjects
- Humans, Mohs Surgery, Neoplasm Recurrence, Local surgery, Retrospective Studies, Carcinoma, Basal Cell pathology, Carcinoma, Basal Cell surgery, Skin Neoplasms pathology, Skin Neoplasms surgery
- Abstract
Mohs micrographic surgery is the preferred surgical option for high-risk basal cell carcinomas. In our institution, the method is exclusively used for the treatment of aggressive and recurrent facial tumours selected via multidisciplinary team meetings and consistently managed using a multidisciplinary approach. The aim of this retrospective patient-record study was to examine the outcomes for basal cell carcinomas managed with Mohs micrographic surgery and to present our experience from multidisciplinary team meetings and interdisciplinary collaborations. All patients treated between September 2009 and March 2019 at Karolinska University hospital were included. In a total of 143 facial basal cell carcinomas in 138 patients, 86 primary and 57 recurrent, the recurrence rate was 4.9% after a median follow-up of 24 months. In regions, where highly specialised Mohs surgeons performing all the steps of the procedure are limited, interdisciplinary collaboration can be an effective strategy for appropriate patient selection and for performing all steps of Mohs surgery with dermatosurgeons eradicating the tumour, pathologists evaluating the histopathology, followed by reconstructive surgery by plastic surgeons. The approach we present here provides a robust and functioning Mohs surgical service during the build-up of the organisation, while providing the opportunity to train new surgeons. Once the clinic has been set up, the multidisciplinary approach should always be considered and applied when dealing with complex cases., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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7. Reconstructive outcomes of Mohs surgery compared with conventional excision: A 13-month prospective study.
- Author
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Wain RA and Tehrani H
- Subjects
- Carcinoma, Basal Cell surgery, Carcinoma, Squamous Cell surgery, Dermatofibrosarcoma surgery, Female, Humans, Hutchinson's Melanotic Freckle surgery, Male, Middle Aged, Neoplasm Recurrence, Local surgery, Neoplasms, Adnexal and Skin Appendage surgery, Prospective Studies, Skin Neoplasms classification, Treatment Outcome, Xanthomatosis surgery, Facial Neoplasms surgery, Mohs Surgery, Plastic Surgery Procedures methods, Skin Neoplasms surgery
- Abstract
Established in 2012, the Mersey Regional Centre for Mohs Surgery is the first UK Mohs service to be led by a Mohs trained Plastic & Reconstructive surgeon. We evaluate the resection requirements and reconstructive techniques of our patient group and compare their surgical outcome to that which would have been gained with conventional excision (CE) and reconstruction for the same lesions. 157 patients were analysed over 13 months. Had CE and reconstruction been used, 56% of patients would have received a more invasive or cosmetically less desirable reconstruction, and 24% of margins would remain incomplete. The outcome was unchanged in 20% of patients. A small but significant subgroup (9%) of patients would have lost fundamental structures e.g. orbital exenteration, or undergone reconstructions unnecessarily crossing aesthetic subunits. Whilst in its infancy, the Plastic & Reconstructive Mohs surgery service has provided a valuable contribution to the care given to patients in the Mersey and Cheshire Skin Cancer Network. Detailed referral criteria, thorough preoperative patient evaluation, and appreciation of the abilities and limits of CE have enabled the service to produce a demonstrable reconstructive benefit in 80% of patients when compared to non-Mohs resection and reconstruction., (Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2015
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8. Some causes of inter-laboratory variation in the results of comet assay.
- Author
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Sirota NP, Zhanataev AK, Kuznetsova EA, Khizhnyak EP, Anisina EA, and Durnev AD
- Subjects
- Animals, Bone Marrow Cells drug effects, Bone Marrow Cells metabolism, Cells, Cultured, DNA Damage drug effects, DNA Damage radiation effects, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Methyl Methanesulfonate toxicity, Mice, Mice, Inbred C57BL, X-Rays adverse effects, Comet Assay standards, Laboratories standards
- Abstract
We performed an inter-laboratory study to determine the variation of comet assay results and to identify its possible reasons. An exchange of slides between Labs in different stages of the comet assay protocol was performed. Because identical slides, durations of alkali treatment and electrophoresis, and similar electric field strengths (2.0 V/cm and 2.14 V/cm) were used, we concluded that the observed inter-laboratory difference in the results is directly associated with the electrophoresis step. In Lab 1, mouse bone marrow cells were exposed to methyl methanesulfonate at concentrations of 10, 25 and 50 μM for 3 h at 37 °C. In Lab 2, cells the same as in Lab 1 were immobilized in LMA on slides and exposed to X-rays at doses of 3-8 Gy. We found that the transportation of slides after lysis or electrophoresis step, as well as different dyes used for scoring did not produce any significant effect on the results. No substantial difference in the data was also revealed when various software packages were used for image analysis. The temperature of the alkaline solution was shown to increase during electrophoresis and, besides, the temperature heterogeneity of the solution took place in the area of the platform, with a maximum in the middle of the chamber. The temperature heterogeneity could affect the rate of conversion of alkali labile sites into single stranded breaks. Thus, it was clearly indicated that real temperature variations during the alkali treatment and electrophoresis were an essential factor in the variability of the results between our Labs., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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9. Modulation of the yeast protein interactome in response to DNA damage.
- Author
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Rochette S, Gagnon-Arsenault I, Diss G, and Landry CR
- Subjects
- Methotrexate pharmacology, Methyl Methanesulfonate pharmacology, RNA, Fungal drug effects, RNA, Messenger metabolism, Saccharomyces cerevisiae drug effects, Saccharomyces cerevisiae growth & development, Saccharomyces cerevisiae metabolism, DNA Damage, Protein Interaction Maps genetics, Saccharomyces cerevisiae Proteins metabolism, Tetrahydrofolate Dehydrogenase genetics
- Abstract
Cells deploy diverse mechanisms to physiologically adapt to potentially detrimental perturbations. These mechanisms include changes in the organization of protein-protein interaction networks (PINs). Most PINs characterized to date are portrayed in a single environmental condition and are thus likely to miss important connections among biological processes. In this report, we show that the yeast DHFR-PCA on high-density arrays allows to detects modulations of protein-protein interactions (PPIs) in different conditions by testing more than 1000 PPIs in standard and in a drug-inducing DNA damage conditions. We identify 156 PPIs that show significant modulation in response to DNA damage. We provide evidence that modulated PPIs involve essential genes (NOP7, EXO84 and LAS17) playing critical roles in response to DNA damage. Additionally, we show that a significant proportion of PPI changes are likely explained by changes in protein localization and, to a lesser extent, protein abundance. The protein interaction modules affected by changing PPIs support the role of mRNA stability and translation, protein degradation and ubiquitylation and the regulation of the actin cytoskeleton in response to DNA damage. Overall, we provide a valuable tool and dataset for the study of the rewiring of PINs in response to environmental perturbations., Biological Significance: We show that the DHFR-PCA is a high-throughput method that allows the detection of changes in PPIs associated with different environmental conditions using DNA damage response as a testbed. We provide a valuable resource for the study of DNA damage in eukaryotic cells. This article is part of a Special Issue: Can Proteomics Fill the Gap Between Genomics and Phenotypes?, (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2014
- Full Text
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10. Chromatin remodelling complex RSC promotes base excision repair in chromatin of Saccharomyces cerevisiae.
- Author
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Czaja W, Mao P, and Smerdon MJ
- Subjects
- Alkylating Agents pharmacology, Cell Cycle Proteins genetics, Chromatin metabolism, Chromatin Assembly and Disassembly, DNA Methylation, DNA-Binding Proteins genetics, Galactokinase genetics, Galactokinase metabolism, Gene Knockdown Techniques, Genome, Fungal, Methyl Methanesulfonate pharmacology, Nuclear Proteins genetics, Saccharomyces cerevisiae drug effects, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics, Transcription Factors genetics, Cell Cycle Proteins metabolism, Chromatin genetics, DNA Repair drug effects, DNA, Fungal genetics, DNA-Binding Proteins metabolism, Nuclear Proteins metabolism, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins metabolism, Transcription Factors metabolism
- Abstract
The base excision repair (BER) pathway is a conserved DNA repair system required to maintain genomic integrity and prevent mutagenesis in all eukaryotic cells. Nevertheless, how BER operates in vivo (i.e. in the context of chromatin) is poorly understood. We have investigated the role of an essential ATP-dependent chromatin remodelling (ACR) complex RSC (Remodels the Structure of Chromatin) in BER of intact yeast cells. We show that depletion of STH1, the ATPase subunit of RSC, causes enhanced sensitivity to the DNA alkylating agent methyl methanesulfonate (MMS) and results in a substantial inhibition of BER, at the GAL1 locus and in the genome overall. Consistent with this observation, the DNA in chromatin is less accessible to micrococcal nuclease digestion in the absence of RSC. Quantitative PCR results indicate that repair deficiency in STH1 depleted cells is not due to changes in the expression of BER genes. Collectively, our data indicates the RSC complex promotes efficient BER in chromatin. These results provide, for the first time, a link between ATP-dependent chromatin remodelling and BER in living cells., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
- Full Text
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11. The plastic & reconstructive Mohs surgery service.
- Author
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Wain RA and Tehrani H
- Subjects
- Dermatology education, Humans, Plastic Surgery Procedures, Surgery, Plastic education, Dermatology organization & administration, Mohs Surgery education, Patient Care Team, Skin Neoplasms surgery, Surgery, Plastic organization & administration
- Abstract
Mohs Micrographic Surgery (MMS) is the current 'gold-standard' for excision of a number of cutaneous lesions and provides a valuable addition to a skin cancer service. The Mersey Regional Centre for Mohs Surgery is the first MMS service in the UK to be led by an MMS trained Plastic and Reconstructive surgeon, and this article describes an overview of the processes involved in establishing such a service., (Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2014
- Full Text
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12. Mass spectrometry-based quantification of the cellular response to methyl methanesulfonate treatment in human cells.
- Author
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Aslanian A, Yates JR 3rd, and Hunter T
- Subjects
- Chromatin metabolism, DNA Damage, HeLa Cells, Humans, Mass Spectrometry, Nuclear Proteins metabolism, Protein Processing, Post-Translational, Antineoplastic Agents, Alkylating toxicity, DNA Repair, Methyl Methanesulfonate toxicity, Proteome metabolism
- Abstract
Faithful transmission of genetic material is essential for cell viability and organism health. The occurrence of DNA damage, due to either spontaneous events or environmental agents, threatens the integrity of the genome. The consequences of these insults, if allowed to perpetuate and accumulate over time, are mutations that can lead to the development of diseases such as cancer. Alkylation is a relevant DNA lesion produced endogenously as well as by exogenous agents including certain chemotherapeutics. We sought to better understand the cellular response to this form of DNA damage using mass spectrometry-based proteomics. For this purpose, we performed sub-cellular fractionation to monitor the effect of methyl methanesulfonate (MMS) treatment on protein localization to chromatin. The levels of over 500 proteins were increased in the chromatin-enriched nuclear lysate including histone chaperones. Levels of ubiquitin and subunits of the proteasome were also increased within this fraction, suggesting that ubiquitin-mediated degradation by the proteasome has an important role in the chromatin response to MMS treatment. Finally, the levels of some proteins were decreased within the chromatin-enriched lysate including components of the nuclear pore complex. Our spatial proteomics data demonstrate that many proteins that influence chromatin organization are regulated in response to MMS treatment, presumably to open the DNA to allow access by other DNA damage response proteins. To gain further insight into the cellular response to MMS-induced DNA damage, we also performed phosphorylation enrichment on total cell lysates to identify proteins regulated via post-translational modification. Phosphoproteomic analysis demonstrated that many nuclear phosphorylation events were decreased in response to MMS treatment. This reflected changes in protein kinase and/or phosphatase activity in response to DNA damage rather than changes in total protein abundance. Using these two mass spectrometry-based approaches, we have identified a novel set of MMS-responsive proteins that will expand our understanding of DNA damage signaling., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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13. Pre-clinical safety evaluation of the synthetic human milk, nature-identical, oligosaccharide 2'-O-Fucosyllactose (2'FL).
- Author
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Coulet M, Phothirath P, Allais L, and Schilter B
- Subjects
- Animals, Animals, Newborn, Cell Line, Tumor, Female, Humans, Infant Formula, Male, Mice, Milk, Human, Mutagenicity Tests, Rats, Rats, Wistar, Salmonella typhimurium drug effects, Salmonella typhimurium genetics, Toxicity Tests, Subacute, Toxicity Tests, Subchronic, Trisaccharides toxicity
- Abstract
In order to match the composition of human breast milk more closely, it is now possible to supplement commercial infant formula (IF) with synthesised oligosaccharides that are chemically identical to human milk oligosaccharides. The safety data generated on a new human-identical milk oligosaccharide (HiMO), 2'-O-Fucosyllactose (2'FL), are presented. Standard in vitro genotoxicity tests were performed. To investigate the toxicological profile in a model representative of the intended target population, 2'FL was administered via gavage in a juvenile adapted sub-chronic rat study at dose levels of 0, 2000, 5000 and 6000 mg/kgbw/day. Fructooligosaccharide (FOS), currently acknowledged as safe and approved for use in IF, was used as a reference high-dose control at 6000 mg/kgbw/day. 2'FL was non-mutagenic in the in vitro assays. Oral administration up to 5000 mg/kgbw/day to rats over 90 days was not associated with any adverse effects based on clinical observations, body weight gain, food consumption, ophthalmoscopy, clinical pathology, organ weights and histopathology findings. Based on this 90-day study, a No Observed Adverse Effect Level (NOAEL) of 5000 mg/kgbw/day for both male and female rats was established for 2'FL. These findings support the safety of synthetic 2'FL for possible use in infant food., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
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14. Comparison of the biological effects of MMS and Me-lex, a minor groove methylating agent: clarifying the role of N3-methyladenine.
- Author
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Monti P, Foggetti G, Menichini P, Inga A, Gold B, and Fronza G
- Subjects
- Adenine physiology, DNA-Directed DNA Polymerase physiology, Humans, Netropsin toxicity, Saccharomyces cerevisiae Proteins physiology, Adenine analogs & derivatives, Methyl Methanesulfonate toxicity, Mutagens toxicity, Netropsin analogs & derivatives
- Abstract
N3-methyladenine (3-mA), generated by the reaction of methylating agents with DNA, is considered a highly toxic but weakly mutagenic lesion. However, due to its intrinsic instability, some of the biological effects of the adduct can result from the formation of the corresponding depurination product [an apurinic (AP)-site]. Previously, we exploited Me-lex, i.e. {1-methyl-4-[1-methyl-4-(3-methoxysulfonylpropanamido)pyrrole-2-carboxamido]-pyrrole-2 carboxamido}propane, a minor groove equilibrium binder with selectivity for A/T rich sequences that efficiently reacts with DNA to afford 3-mA as the dominant product, to probe the biology of this lesion. Using human p53 cDNA as a target in a yeast system, a weak increase in mutagenicity was observed in the absence of Mag1 (3-methyladenine-DNA glycosylase 1, mag1), the enzyme devoted to remove 3-mA from DNA. Moreover, a significant increase in mutagenicity occurred in the absence of the enzymes involved in the repair of AP-sites (AP endonucleases 1 and 2, apn1apn2). Since methyl methanesulfonate (MMS) has been extensively used to explore the biological effects of 3-mA, even though it produces 3-mA in low relative yield, we compared the toxicity and mutagenicity induced by MMS and Me-lex in yeast. A mutagenesis reporter plasmid was damaged in vitro by MMS and then transformed into wild-type and Translesion Synthesis (TLS) Polζ (REV3) and Polη (RAD30) deficient strains. Furthermore, a mag1rad30 double mutant strain was constructed and transformed with the DNA plasmid damaged in vitro by Me-lex. The results confirm the important role of Polζ in the mutagenic bypass of MMS and Me-lex induced lesions, with Polη contributing only towards the bypass of Me-lex induced lesions, mainly in an error-free way. Previous and present results point towards the involvement of AP-sites, derived from the depurination of 3-mA, in the observed toxicity and mutagenicity., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2014
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15. Dietary flavonoids bind to mono-ubiquitinated annexin A1 in nuclei, and inhibit chemical induced mutagenesis.
- Author
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Hirata F, Harada T, Corcoran GB, and Hirata A
- Subjects
- DNA biosynthesis, Flavonoids metabolism, Humans, Mutagenesis drug effects, Thymidine Kinase genetics, Annexin A1 metabolism, Antimutagenic Agents pharmacology, Cell Nucleus metabolism, Flavonoids pharmacology, Ubiquitination
- Abstract
In order to investigate the mechanisms of anti-mutagenic action by dietary flavonoids, we investigated if they inhibit mutation of the thymidine kinase (tk) gene in L5178Ytk(±) lymphoma cells. Silibinin, quercetin and genistein suppressed mutation of the tk gene induced in L5178Ytk(±) lymphoma cells by methyl methanesulfonate (MMS) and As(3+). Flavone and flavonol were less effective. To establish that mutation of the tk gene in L5178Ytk(±) lymphoma cells by MMS and As(3+) is mediated through mono-ubiquitinated annexin A1, L5178Ytk(±) lymphoma cells were treated with annexin A1 anti-sense oligonucleotide. The treatment reduced mRNA as well as protein levels of annexin A1, and suppressed mutation of the tk gene. Nuclear extracts from L5178Ytk(±) lymphoma cells catalyzed translesion DNA synthesis with an oligonucleotide template containing 8-oxo-guanosine in an annexin A1 dependent manner. This translesion DNA synthesis was inhibited by the anti-mutagenic flavonoids, silibinin, quercetin and genistein, in a concentration dependent manner, but only slightly by flavone and flavonol. Because these observations implicate involvement of annexin A1 in mutagenesis, we examined if flavonoids suppress nuclear annexin A1 helicase activity. Silibinin, quercetin and genistein inhibited ssDNA binding, DNA chain annealing and DNA unwinding activities of purified nuclear mono-ubiquitinated annexin A1. Flavone and flavonol were ineffective. The apparent direct binding of anti-mutagenic flavonoids to the annexin A1 molecule was supported by fluorescence quenching. Taken together, these findings illustrate that nuclear annexin A1 may be a novel and productive target protein of prevention for DNA damage induced gene mutation, ultimately conferring cancer chemoprevention., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2014
- Full Text
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16. Exposure profiling of reactive compounds in complex mixtures.
- Author
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Goel S, Evans-Johnson JA, Georgieva NI, and Boysen G
- Subjects
- Animals, Biomarkers analysis, Biomarkers blood, Chromatography, Liquid, Complex Mixtures chemistry, Female, Hemoglobins analysis, Hemoglobins chemistry, Humans, Mice, Mice, Inbred C57BL, Tandem Mass Spectrometry, Valine analysis, Valine chemistry, Carcinogens, Environmental analysis, Complex Mixtures blood, Environmental Exposure analysis
- Abstract
Humans are constantly exposed to mixtures, such as tobacco smoke, exhaust from diesel, gasoline or new bio-fuels, containing several 1000 compounds, including many known human carcinogens. Covalent binding of reactive compounds or their metabolites to DNA and formation of stable adducts is believed to be the causal link between exposure and carcinogenesis. DNA and protein adducts are well established biomarkers for the internal dose of reactive compounds or their metabolites and are an integral part of science-based risk assessment. However, technical limitations have prevented comprehensive detection of a broad spectrum of adducts simultaneously. Therefore, most studies have focused on measurement of abundant individual adducts. These studies have produced valuable insight into the metabolism of individual carcinogens, but they are insufficient for risk assessment of exposure to complex mixtures. To overcome this limitation, we present herein proof-of-principle for comprehensive exposure assessment, using N-terminal valine adduct profiles as a biomarker. The reported method is based on our previously established immunoaffinity liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with modification to enrich all N-terminal valine alkylated peptides. The method was evaluated using alkylated peptide standards and globin reacted in vitro with alkylating agents (1,2-epoxy-3-butene, 1,2:3,4-diepoxybutane, propylene oxide, styrene oxide, N-ethyl-N-nitrosourea and methyl methanesulfonate), known to form N-terminal valine adducts. To demonstrate proof-of-principle, the method was successfully applied to globin from mice treated with four model compounds. The results suggest that this novel approach might be suitable for in vivo biomonitoring., (Copyright © 2013. Published by Elsevier Ireland Ltd.)
- Published
- 2013
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17. Genotoxicity of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™).
- Author
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Nakano M, Suzuki H, Imamura T, Lau A, and Lynch B
- Subjects
- Animals, Cell Line, Cells, Cultured, Cricetulus, Female, Humans, Lung cytology, Lymphocytes drug effects, Mice, Mice, Inbred ICR, Mutagenicity Tests, Salmonella typhi drug effects, Salmonella typhi genetics, PQQ Cofactor toxicity
- Abstract
The genotoxic potential of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) was evaluated in a battery of genotoxicity tests. The results of the bacterial mutation assay (Ames test) were negative. Weak positive results were obtained in 2 separate in vitro chromosomal aberration test in Chinese hamster lung (CHL) fibroblasts. Upon testing in an in vitro chromosomal aberration test in human peripheral blood lymphocytes, no genotoxic activity of PQQ was noted. In the in vivo micronucleus assay in mice, PQQ at doses up to 2,000 mg/kg body weight demonstrated that no genotoxic effects are expressed in vivo in bone marrow erythrocytes. The weak responses in the in vitro test CHL cells were considered of little relevance under conditions of likely human exposure. PQQ disodium was concluded to have no genotoxic activity in vivo., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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18. Cytoplasmic localization of Hug1p, a negative regulator of the MEC1 pathway, coincides with the compartmentalization of Rnr2p-Rnr4p.
- Author
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Ainsworth WB, Hughes BT, Au WC, Sakelaris S, Kerscher O, Benton MG, and Basrai MA
- Subjects
- Gene Expression Regulation, Fungal, Intracellular Signaling Peptides and Proteins genetics, Protein Serine-Threonine Kinases genetics, Ribonucleoside Diphosphate Reductase genetics, Ribonucleotide Reductases genetics, Saccharomyces cerevisiae Proteins genetics, Cytoplasm metabolism, Intracellular Signaling Peptides and Proteins metabolism, Protein Serine-Threonine Kinases metabolism, Ribonucleoside Diphosphate Reductase metabolism, Ribonucleotide Reductases metabolism, Saccharomyces cerevisiae Proteins metabolism
- Abstract
The evolutionarily conserved MEC1 checkpoint pathway mediates cell cycle arrest and induction of genes including the RNR (Ribonucleotide reductase) genes and HUG1 (Hydroxyurea, ultraviolet, and gamma radiation) in response to DNA damage and replication arrest. Rnr complex activity is in part controlled by cytoplasmic localization of the Rnr2p-Rnr4p subunits and inactivation of negative regulators Sml1p and Dif1p upon DNA damage and hydroxyurea (HU) treatment. We previously showed that a deletion of HUG1 rescues lethality of mec1Δ and suppresses dun1Δ strains. In this study, multiple approaches demonstrate the regulatory response of Hug1p to DNA damage and HU treatment and support its role as a negative effector of the MEC1 pathway. Consistent with our hypothesis, wild-type cells are sensitive to DNA damage and HU when HUG1 is overexpressed. A Hug1 polyclonal antiserum reveals that HUG1 encodes a protein in budding yeast and its MEC1-dependent expression is delayed compared to the rapid induction of Rnr3p in response to HU treatment. Cell biology and subcellular fractionation experiments show localization of Hug1p-GFP to the cytoplasm upon HU treatment. The cytoplasmic localization of Hug1p-GFP is dependent on MEC1 pathway genes and coincides with the cytoplasmic localization of Rnr2p-Rnr4p. Taken together, the genetic interactions, gene expression, and localization studies support a novel role for Hug1p as a negative regulator of the MEC1 checkpoint response through its compartmentalization with Rnr2p-Rnr4p., (Published by Elsevier Inc.)
- Published
- 2013
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