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Hydrothermal carbonization (HTC) is emerging as a promising technology for converting waste biomass into a dense coal-like product known as hydrochar. Oily sludge (OS), known for its toxic, carcinogenic, and mutagenic effects, is classified as hazardous waste, posing negative implications for both humans and the ecosystem if improperly disposed. Consequently, the conversion of hazardous oily sludge into safe and renewable products offers significant benefits. To investigate the HTC process further, a design matrix consisting of 20 experimental runs was utilized, integrating results obtained from HTC experiments as input for response surface methodology (RSM). The variables were restricted to a temperature range of 175°C–250°C, a time span of 0.5–2 h, and a solid load range of 3%–8%. Analyzing the data, it was observed that raw sludge initially exhibited a hydrogen-to-carbon (H/C) ratio of 1.33 and an oxygen-to-carbon (O/C) ratio of 0.59. However, following HTC processing, these ratios decreased significantly to 0.18 (at 250°C, 2 h, 3% solid load) and 0.691 (at 250°C, 1 h, 5.5% solid load), respectively. These decreases can be attributed to dehydration and decarboxylation reactions that occurred during the HTC process. The model equation developed using RSM was: carbon content = 66.29 + 6.98A + 0.3515B–2.60C – 0.0412AB + 0.1730AC – 0.0037BC – 1.83A2 + 0.8005B2 – 0.945C2. Carbon densification increased from 1.09 to 1.45 with hydrochar retaining 66.5%–77.65% of the carbon. HTC holds promise as a sustainable technology for carbon and energy recovery. [ABSTRACT FROM AUTHOR]

Purine‐pyrimidine repeats (PPRs) can form left‐handed Z‐form DNA and induce DNA double‐strand breaks (DSBs), posing a risk for genomic rearrangements and cancer. The zinc finger (ZF) and BTB domain‐containing protein 43 (ZBTB43) is a transcription factor containing two Cys2‐His2 (C2H2) and one C3H1 zinc fingers and plays a crucial role in maintaining genomic and epigenomic integrity by converting mutagenic Z‐form PPRs to the B‐form in prospermatogonia. Despite its importance, the molecular mechanism underlying the recognition of PPRs by ZBTB43 remains elusive. In this study, we determined the X‐ray crystal structure of the ZBTB43 ZF1‐3 in complex with the B‐form DNA containing the CA repeats sequence. The structure reveals that ZF1 and ZF2 primarily recognize the CACA sequence through specific hydrogen‐bonding and van der Waals contacts via a quadruple center involving Arg389, Met411, His413, and His414. These interactions were further validated by fluorescence‐based DNA‐binding assays using mutated ZBTB43 variants. Our structural investigation provides valuable insights into the recognition mechanism of PPRs by ZBTB43 and suggests a potential role for ZBTB43 in the transformation of Z‐DNA to B‐DNA, contributing to the maintenance of genomic stability. [ABSTRACT FROM AUTHOR]

Background: Fusobacterium nucleatum (F. nucleatum) is one of the key tumorigenic bacteria in colorectal cancer (CRC), yet how F. nucleatum is involved in colorectal cancer carcinogenesis remains unknown. Results: In the present study, we carried out PathSeq analysis on RNA sequencing data from the 430 primary colon adenocarcinomas in TCGA database to assess the relationship between patients' survival and F. nucleatum abundance. Among patients with cecum and ascending colon tumors, we found that F. nucleatum transcriptome abundance is positively correlated with mutation load. We further demonstrated that patients with both high tumoral abundance of F. nucleatum and high mutation load exhibited poorer survival and DNA damage. We furthermore determined that F. nucleatum-conditioned medium (Fn. CM) induces DNA damage in both in vitro and in vivo studies. In addition, two F. nucleatum-secreted mutagens, namely DL-homocystine and allantoic acid, were identified to lead to DNA damage. Conclusions: Our finding delineates the genotoxicity of F.nucleatum-secreted mutagens, which provides a basis for further work to investigate the role of F. nucleatum in the pathogenicity of CRC. [ABSTRACT FROM AUTHOR]

Citrus, one of the most popular fruit crops grown worldwide, has high nutritional, medicinal and commercial value. This experiment aimed to investigate the effects of gamma radiation with various doses, including 0 Gy, 5Gy, 10 Gy, 15 Gy, 20 Gy, 25Gy, 30 Gy, 35 Gy, 40 Gy and 45 Gy of cobalt 60 sources on acid lime variety Agamalai citrus, (Citrus aurantifolia). The study was carried out at the Horticulture College and Research Institute in Periyakulam. The mutagenic efficiency and effectiveness were evaluated using the frequency of chlorophyll mutations and the biological damage in M1 plants. The stomatal index reduces (19.62 %-13.99%) with increasing treatment dose, compared to control (20.39%), although guard cell dimensions, such as length (6.09 µm) in 15 Gy and breadth (4.56 µm) in 5 Gy increase with higher dose treatment than untreated (3.71 µm, 3.54 µm). Identifying the mutagenic efficiency and effectiveness of the mutagen and maximising the lethal dosage is the first stage in any mutagenesis research. This work will serve as a foundation for subsequent gamma-irradiation studies in acidlime to generate desirable mutants. [ABSTRACT FROM AUTHOR]

Bis-(2-Chloroisopropyl) ether (BCIPE) was used as a solvent for fats, greases, paint, varnish removers, and in spotting and cleaning solutions. However, BCIPE has not been commercially manufactured or used for numerous years. In experimental animal studies, BCIPE is moderately toxic following acute oral, dermal, and inhalation routes of exposure. BCIPE is a severe eye irritant but not a dermal irritant or dermal sensitizer. BCIPE was not genotoxic or mutagenic in in vitro and in vivo assays; it was not toxic in a 3-generation reproductive dietary study in rats. Short-term, repeated inhalation and oral exposure in rats produced increased liver and kidney weights and congestion; dermal exposure in rabbits did not produce any observable adverse effects. BCIPE did not produce a statistically significant increase in tumors in two different 2-year dietary studies in mice and rats. In mice, technical grade BCIPE produced increased incidences of alveolar/bronchiolar adenomas in females, hepatocellular carcinomas in males, and a low incidence of forestomach hyperplasia (in both sexes at the high-dose). Further investigation with technical grade BCIPE concluded that these effects were species- and dose-specific with limited, if any, relevance to humans. The NOAEL of 400 ppm (15 mg/kg/day) from the 2-year dietary study in female rats was considered the point of departure for the health-based WEEL derivation. After adjustment for duration of exposure, interindividual variability, and intraindividual variability, an 8-h time-weighted average (TWA) WEEL value of 3 ppm (21 mg/m3) was derived. This exposure limit is expected to provide a significant margin of safety against any potential adverse health effects in workers. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Streptococcus thermophilus is a common starter in yogurt production and plays an important role in the dairy industry. In this study, a galactose-positive (Gal+) mutant strain, IMAU20246Y, was produced using the chemical mutagen N-methyl-N′-nitro-N-nitrosoguanidine (NTG) from wild-type S. thermophilus IMAU20246, which is known to have good fermentation characteristics. The sugar content of milk fermented by either the mutant or the wild type was determined using HPLC; metabolism of lactose and galactose was significantly increased in the mutant strain. In addition, we used response surface methodology to optimize components of the basic M17 medium for survival ratio of the mutant strain. Under these optimal conditions, the viable counts of mutant S. thermophilus IMAU20246Y reached 4.15 × 108 cfu/mL and, following freeze-drying in the medium, retained cell viability of up to 67.42%. These results are conducive to production of a high-vitality starter culture and development of "low sugar, high sweetness" dairy products. [ABSTRACT FROM AUTHOR]

The current study was initiated to assess mungbean [Vigna radiata (L.) R. Wilczek] mutant lines for yield and their attributes in the mutation generation third (M3) generation using an augmented block design. Note that 1200 mutated mungbean lines were selected from the γ-irradiated (400–700 Gy) population and distributed into 21 blocks, along with three popular varieties (checks) replicated in each block. To evaluate mean performance, variance, and population genetics, the observations on days to flowering, days to maturity, plant height (cm), number of clusters per plant, number of pods per plant, pod length (cm), protein percentage, seed index, and seed yield (g) were measured and analyzed. All the lines under consideration showed highly significant variations for all the variables, except for days to flowering. Seventy-nine mutant lines were found to have significantly better yield attributes than checks and are currently being evaluated under station trial. Skewness and kurtosis analysis unveiled the presence of gene interactions, offering opportunities for targeted improvement and efficacy of γ rays as a mutagen, facilitating the release of variability within the population. Future mungbean breeding programs will benefit from the successful isolation of mutant plants with yield-enhancing traits, such as up to 20 clusters per plant, 71 pods per plant, 8.55 cm pod length, 26.69% protein content (5% higher than parent), and 29 gram seeds per plant. In early selection cycles without the need for replicated trials, this study demonstrated the effectiveness of the mutagen and augmented design in creating novel variations, evaluating and identifying superior genotypes with improved yield potential [ABSTRACT FROM AUTHOR]

DNA polymerase ζ (Pol ζ) plays an essential role in replicating damaged DNA templates but contributes to mutagenesis due to its low fidelity. Therefore, ensuring tight control of Pol ζ's activity is critical for continuous and accurate DNA replication, yet the specific mechanisms remain unclear. This study reveals a regulation mechanism of Pol ζ activity in human cells. Under normal conditions, an autoinhibition mechanism keeps the catalytic subunit, REV3L, inactive. Upon encountering replication stress, however, ATR-mediated phosphorylation of REV3L's S279 cluster activates REV3L and triggers its degradation via a caspase-mediated pathway. This regulation confines the activity of Pol ζ, balancing its essential role against its mutations causing potential during replication stress. Overall, our findings elucidate a control scheme that fine tunes the low-fidelity polymerase activity of Pol ζ under challenging replication scenarios. DNA polymerase ζ (Pol ζ) maintains continuity but impairs accuracy during DNA replication. Here, the authors report a mechanism by which human cells precisely control the essential, yet mutagenic, activity of Pol ζ to ensure both continuation and fidelity during DNA replication challenges. [ABSTRACT FROM AUTHOR]

Clustered DNA damage, when multiple lesions are generated in close proximity, has various biological consequences, including cell death, chromosome aberrations, and mutations. It is generally perceived as a hallmark of ionizing radiation. The enhanced mutagenic potential of lesions within a cluster has been suggested to result, at least in part, from the selection of the strand with the mutagenic lesion as the preferred template strand, and that this process is relevant to the tolerance of persistent single-strand breaks generated during an attempted repair. Using a plasmid-based assay in Escherichia coli, we examined how the strand bias is affected in mutant strains deficient in different DNA polymerase I activities. Our study revealed that the strand-displacement and 5′-flap endonuclease activities are required for this process, while 3′-to-5′ exonuclease activity is not. We also found the strand template that the mutagenic lesion was located on, whether lagging or leading, had no effect on this strand bias. Our results imply that an unknown pathway operates to repair/tolerate the single-strand break generated at a bi-stranded clustered damage site, and that there exist different backup pathways, depending on which DNA polymerase I activity is compromised. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Infiltrative follicular variant of papillary thyroid carcinoma (IFVPTC) exhibits nuclear characteristics typical of papillary thyroid carcinoma (PTC) but demonstrates a follicular growth pattern. The diagnosis of IFVPTC presenting with atypical nuclear features of PTC poses challenges for both preoperative cytopathology and postoperative histopathology. In such cases, molecular markers are needed to serve as diagnostic aids. Given the limited knowledge of IFVPTC's genomic features, this study aimed to characterize its genetic alterations and identify clinically relevant molecular markers.Whole‐exome sequencing of 50 IFVPTC tumor–normal pairs identified single‐nucleotide variants, somatic copy number alterations (sCNAs), and subclonal architecture. Key mutations were verified via polymerase chain reaction and Sanger sequencing, whereas valuable biomarkers were validated via immunohistochemistry (IHC).This study found that endogenous processes rather than exogenous mutagens dominated the shaping of the genome of IFVPTC during tumorigenesis. BRAF V600E was the only common trunk mutation and significantly mutated gene in IFVPTC. Subcloning analysis found that most IFVPTC samples harbored two or more coexisting clones. sCNA analysis revealed that human leukocyte antigen C (HLA‐C) and HLA‐A were significantly amplified. Subsequent IHC investigations indicated that HLA‐C shows promise in averting the misclassification of challenging‐to‐interpret IFVPTC and invasive encapsulated follicular variant of PTC (I‐EFVPTC) as noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP). Although there were several similarities between classic PTC and IFVPTC, they differed significantly in their sCNA patterns.This study provides valuable insights into IFVPTC's genetic alterations and highlights the potential of HLA‐C IHC to distinguish challenging‐to‐interpret IFVPTC and I‐EFVPTC from NIFTP, which will enhance the understanding of its molecular features for improved diagnosis and management. [ABSTRACT FROM AUTHOR]

Induction of polyploidy can be achieved using chemical mutagen or antimitotic compounds that affect cell division, resulting in doubling number of chromosomes. A new inducer for chromosome doubling mutation agent-bio-catharantin-may be used. This report determined the mortality rate of bio-catharantin used for mutation induction experiments in shallot plants. Two sets of experiments were arranged in a two factorial randomized block design, i.e. five levels of biocatharantin concentration treatment (0.0, 2.5, 5.0, 10.0, and 15.0%) combined with soaking periods of 6-, 12-, and 24-h. Each combination was repeated three times, with five seed bulbs in each combination. The result shows that the mortality rate of shallot tends to increase with increasing concentration and soaking time. A high percentage of the mortality rate was found at all concentrations other than control at 24-h soaking time. Hence, the mortality rate of prolonged soaking (24 h) is greater at higher concentrations. However, at lower concentrations of 2.5 and 5% for 6- and 12-h soaking time the mortality rate was low (13 and 27%, 7 and 60%, respectively). Meanwhile, at 10%, the result shows relatively high mortality rates (13 and 73%, respectively). Administration of bio-catharantin at 5 and 10% with a 12-h soaking period causes optimal mortality rate, whereas the germination rate shows the opposite trend. To find the accuracy of the efficacy of bio-catharantin concentration between 5-10%, we introduced 7.5% in the second experiment. The concentration of 7.5% has a significant effect on leaf diameter, where it becomes smaller as inhibited by increased concentration (2.5 and 5.0%) but becomes larger again at 7.5% (0.59 mm) nearing control (0.70 mm) and drops again to 0.23 mm (10%). This is not usually the trend of inhibition when a larger concentration is used except when polyploidization has taken effect, presumably at 7.5% bio-catharantin with a 12-h immersion period. [ABSTRACT FROM AUTHOR]

The International Agency for Research on Cancer has classified N‐nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA‐directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA‐induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA‐directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA. N‐Nitrosodiethylamine (NDEA) is a potential carcinogen and mutagen. Their carcinogenic action is not limited to a certain target organ but can affect various organs and organ systems. It induces oxidative stress and cellular injury due to higher formation of reactive oxygen species and alters antioxidant system in the tissues. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter antioxidant line to cause malignancy in different parts of animal body along with its protective agents. [ABSTRACT FROM AUTHOR]

Background: The human skin, as the body's largest organ, is particularly sensitive to many chemical mutagens and carcinogens encountered in daily life. Skin cancer has become a notable global health concern, partly due to increased exposure to environmental pollutants and UV rays. Various treatments are available to treat skin cancer. Imiquimod is approved for the treatment of actinic keratosis and basal cell carcinoma. The present investigation aimed to develop nanoemulsion-based gel with imiquimod (2.5% w/w) and carbopol ultrez 10 NF using a modified method to enhance the solubility, permeation, and therapeutic effectiveness of imiquimod to treat skin cancer. Combinations of rose oil and oleic acid, with Tween 20/Propylene glycol as Smix, were used in the formulation. The formulation underwent evaluation for parameters such as % drug content, in vitro drug diffusion studies, viscosity, skin irritation, in vitro cytotoxicity assay (MTT assay) and the DMBA/ croton oil skin cancer in vivo model. Results: The formulation showed a minimum globule size of 118 nm, a zeta potential– 56.26 mV, a PDI of 0.378 and a drug content of 99.77%. In vitro drug release exhibited 45.00% of imiquimod release within 8 h, while approximately 34.32% release was found from the commercial cream. The imiquimod-loaded nanoemulsion-based gel showed significant cytotoxicity (p < 0.001) against the A431 cell line compared to Imiquad cream. The IC50 value of the imiquimod-loaded nanoemulsion-based gel was noted to be 10.76 ± 2.54 µg/mL. In vivo results showed a significant reduction in tumor incidence (16.66%), tumor volume (140.26 ± 3.48 mm3), tumor burden (5.50 mm3) and tumor mass (0.66 ± 0.05 g) compared with the DMBA/croton oil carcinogen treatment control group. Histopathological finding showed the absence of keratinized pearls, epidermal hyperplasia, and acanthosis in the formulation treated group. Conclusion: The results revealed that the nanoemulsion-based gel, with half the IMQ concentration of the commercial cream and incorporating Carbopol Ultrez 10NF, is a promising method for treating skin carcinogenesis. It potentially reduces dose-dependent side effects and demonstrating enhanced efficacy. [ABSTRACT FROM AUTHOR]

AbstractThe presence of impurities in active pharmaceutical ingredients (APIs) and drug products represents a risk to patients’ health. Such substances are related to diverse side effects and may have mutagenic potential. That’s why it is necessary to establish acceptable limits for these by-products, to minimize the risk associated with medicinal therapy. This work focused on presenting a critical review of relevant points related to the presence of impurities in pharmaceuticals. The main legislation and guidelines from the FDA, EMA, ICH, and Pharmacopeias about the subject were evaluated, and recent articles related to the topic were searched in Scopus, ScienceDirect, PubMed, and Web of Science from 2013 to 2023. Additionally, the analytical techniques used for quantifying impurities were discussed, along with relevant tests for assessing the toxicological and mutagenic risks of these by-products. Recent legislation, including ICH Q3A (R2), ICH Q3B (R2), ICH M7 (R2), ICH Q3D (R2), ICH Q3C (R9), ICH Q3E, ICH Q6A, ICH M3 (R2), as well as FDA and EMA guidelines, highlights a comprehensive and effective framework for controlling impurities in pharmaceuticals. Despite this, there remains a lack of harmonization and standardized procedures across different regions. From the review of scientific literature, we observed that advancements in analytical techniques have significantly improved the sensitivity and selectivity in detecting impurities and degradation products. This underscores the ongoing commitment of health agencies and the pharmaceutical industry to ensure the safety and efficacy of medicinal products. [ABSTRACT FROM AUTHOR]

Sulfonate esters are a class of organic impurities that includes highly potent mutagenic substances that typically need to be controlled down to a low ppm level in pharmaceutical development. In this work, two genotoxic impurities of sulfonate esters in Posaconazole, for example, ((3S,5R)‐5‐((1H‐1,2,4‐triazol‐1‐yl)methyl)‐5‐(2,4‐difluorophenyl)tetrahydrofuran‐3‐yl)methyl‐4‐methylbenzenesulfonate and (2S,3S)‐3‐ (4‐(4‐(4‐(4‐(((3R,5R)‐5‐((1H‐1,2,4‐triazol‐1‐yl)methyl)‐5‐(2,4‐difluorophenyl)tetrahydrofuran‐3‐yl)methoxy)phenyl)piperazin‐1‐yl)phenyl)‐5‐oxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐1‐yl)pentan‐2‐yl‐4‐methylbenzenesulfonate, were synthesized and characterized. The genotoxicity which was evaluated by two (quantitative) structure‐activity relationships prediction methodologies showed positive. Furthermore, a novel high‐performance liquid chromatography‐tandem mass spectrometry limit test method for detecting these two impurities in Posaconazole has been established and validated. The chromatographic separation of analytes was conducted on an ACQUITY BEH C18 column, and performed with 0.05% methanoic acid‐water and 0.05% methanoic acid‐acetonitrile as mobile phases A and B, respectively. Six batches of commercial‐scale Posaconazole samples were detected by the validated method and the results were in accordance with the Food and Drug Administration acceptance criteria for the genotoxic impurities in drug substances. Finally, a tentative mechanism for these two impurities was proposed, they are generally accepted to undergo an SN2‐type reaction, resulting in 7‐methylguanine as the predominant adduct in double‐stranded DNA. [ABSTRACT FROM AUTHOR]

Mutagenic effectiveness and efficiency are the most important factors determining the success of mutation breeding, a coherent tool for quickly enhancing diversity in crops. This study was carried out at Lovely Professional University's agricultural research farm in Punjab, India, during the year 2023. The experimental design followed a randomized complete block design (RCBD) with three replications. The experiment aimed to assess the effect of three chemical mutagens, sodium azide (SA), ethyl methyl sulphonates (EMSs), and methyl methane sulfonate (MMS), at three different concentrations (0.2%, 0.4%, and 0.6%), in SL958 and SL744 soybean varieties to select the mutant exhibiting the highest yield. The data were collected and analysed using a two-way ANOVA test through SPSS software (version 22), and the means were separated using Duncan's multiple range test (DMRT) at the 5% level of significance. Between the two varieties, the highest seed germination percentage (76.0% seedlings/plot) was recorded in SL958 (0.4% SA), while the lowest (30.33% seedlings/plot) was observed in 0.6% MMS as compared to the control (53% and 76% in SL744 and SL958 at 10 days after sowing, respectively). Several weeks after sowing, the average plant height was observed to be higher (37.84 ± 1.32 cm) in SL958 (0.4% SA) and lower (20.58 ± 0.30 cm) in SL744 (0.6% SA), as compared to the controls (SL958: 26.09 ± 0.62 cm and SL744: 27.48 ± 0.74 cm). The average leaf count was the highest (234.33 ± 3.09 tetrafoliate leaves/plant) in SL958 (0.4% SA) while it was the lowest (87 leaves/plant) in 0.6% MMS as compared to the control (SL744 180.00 ± 1.63 and SL958 160.73 ± 1.05). The highest total leaf areas recorded in the SL958 and SL744 M1plants were 3625.8 ± 1.43 cm2 and 2311.03 ± 3.65 cm2, respectively. Seeds of the SL958 variety treated with 0.4% SA resulted in the development of tetrafoliate leaves with a broad leaf base and the maximum yield (277.55 ± 1.37 pods/plant) compared to the narrow pentafoliate leaves obtained through the treatment with EMS. Meanwhile, in the SL744 variety, the same treatment led to tetrafoliate leaves with a comparatively lower yield of 206.54 ± 23.47 pods/plant as compared to the control (SL744 164.33 ± 8.58 and SL958 229.86 ± 0.96). The highest protein content (47.04 ± 0.87% TSP) was recorded in the SL958 (0.4% SA) M2 seeds followed by a content of 46.14 ± 0.64% TSP in the SL744 (0.4% SA) M2 seeds, whereas the lowest content (38.13 ± 0.81% TSP) was found in SL958 (0.6% MMS). Similar observations were recorded for the lipid and fibre content. The 0.4% SA treatment in SL958 proved to be efficient in generating the highest leaf area (tetrafoliate leaves) and a reasonable yield of M1 (the first generation after mutation) plants. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to analyze the clinical characteristics of patients with Van der Woude syndrome (VWS) and to detect variations in each patient. Finally, the combination of genotype and phenotype can make a clear diagnosis of VWS patients with different phenotype penetrance. Methods: Five Chinese VWS pedigree were enrolled. Whole exome sequencing of the proband was performed, and the potential pathogenic variation was further verified by Sanger sequencing in the patient and their parents. The human mutant IRF6 coding sequence was generated from the human full-length IRF6 plasmid by site-directed mutagenesis and cloned into the GV658 vector, RT-qPCR and Western blot were used to detect the expression of IRF6. Results: We found one de novo nonsense variation (p. Gln118Ter) and three novel missense variations (p. Gly301Glu, p. Gly267Ala, and p. Glu404Gly) co-segregated with VWS. RT-qPCR analysis revealed that p. Glu404Gly significantly reduced the expression level of IRF6 mRNA. Western blot of cell lysates confirmed that IRF6 p. Glu404Gly abundance levels were lower than those for IRF6 wild type. Conclusions: This discovery of the novel variation (IRF6 p. Glu404Gly) expands the spectrum of known variations in VWS in Chinese humans. Genetic results combined with clinical phenotypes and differential diagnosis points from other diseases can make a definitive diagnosis and provide genetic counseling for families. [ABSTRACT FROM AUTHOR]

To induce polyploidy in rhododendrons, different experimental materials of four Rhododendron species (2n = 2x = 26) were treated with colchicine and oryzalin as chemical mutagens. Three materials from R. fortunei, namely, seeds, cotyledons, and adventitious buds, were treated, and the highest tetraploid induction rate (15.64%) was observed in cotyledons treated with 20 mg·L− 1 oryzalin for 4 d. Two materials (stem tips and stem bases) were treated in R. simsii, and the highest tetraploid induction rate (4.04%) was achieved with 0.14% colchicine after soaking the stem tips for 48 h. However, when we treated the stem bases, the chimerism occurrence rate was up to 30.00%. In addition, polyploidy induction in R. ovatum was carried out at two colchicine concentrations (0.12 and 0.14%) with two materials (stem tip and stem base), which resulted in a higher chimeric rate. Three materials (stem tip, stem base, and adventitious buds) of R. molle were used, but no polyploidy was found. Polyploid identification was performed through stomatal observation and flow cytometry. Polyploid plants had larger and sparser stomata than diploid plants. Furthermore, morphological measurements revealed that the size of the stomata and leaves in tetraploid plants was larger than that in diploid plants. Stomatal density was decreased in tetraploid plants compared to diploid plants. Flow cytometry analysis identified tetraploids in the mutant plants of R. fortunei and R. simsii. Phenotypic analyses showed that tetraploid plants had smaller, rounder leaves and darker leaf colors than diploid plants. In summary, we compared the induced polyploid rhododendrons using different methods, which is of great significance for cultivating new rhododendron varieties with good ornamental properties and high resistance and for developing the rhododendron industry in China.Key message: In this research, we have tested various methods and different materials for the polyploidy induction in rhododendrons, and analyzed the morphological characteristics of polyploid plants. [ABSTRACT FROM AUTHOR]

Kodomillet is a staple food grain in semi-arid regions also known for its excessive free radical quenching capacity. Due to the cleistogamous flowering pattern, recombination breeding has limited scope in this crop. This study was formulated to induce genetic variation in kodo millet by induced mutagenesis involving two varieties, ATL 1 and CKMV 1. Seeds were irradiated with five different gamma-ray doses namely., 300 Gy, 400 Gy, 500 Gy, 600 Gy and 700 Gy, respectively and LD50 was determined based on reduction in root and shoot lengths. The gamma ray dosage and root and shoot lengths were observed to be inversely proportional. Chlorophyll mutants namely., Albino, Xantha, Xantha viridis, Chlorina and Striata were observed in all treatments except 700 Gy in both the genotypes in M1 generation. Mutagenic effectiveness and efficiency were calculated based on the frequency of chlorophyll mutations in M1 plants. Two early maturing novel mutants from ATL 1 and three high yielding mutants from CKMV 1 at 400 Gy dose and 500 Gy dose, respectively were isolated. Mutagenic treatments were efficient in creating genetic variation for morphological traits. These mutants would be useful in improvement of kodo millet. [ABSTRACT FROM AUTHOR]

The use of topical photoprotection is necessary to reduce adverse effects caused by excessive exposure to ultraviolet radiation. Despite the high standards set for UV filters, many of them may contribute to the occurrence of adverse effects. The newly synthesised compound K-116, the (E)-cinnamoyl xanthone derivative, could be an alternative. We conducted extended in vitro safety evaluation of compound K-116. The research included assessment of irritation potential on skin tissue, evaluation of penetration through the epidermis, and assessment of phototoxicity, and mutagenicity. Additionally, the eco-safety of compound K-116 was evaluated, including an examination of its degradation pathway in the Cunninghamella echinulata model, as well as in silico simulation of the toxicity of both the parent compound and its degradation products. The research showed that compound K-116 tested in future application conditions is deprived of skin irritant potential additionally it does not penetrate through the epidermis. Results showed that K-116 concentrate is not phototoxic and not mutagenic. The eco-safety studies showed that it undergoes biodegradation in 27% in Cunninghamella echinulata model. The parent compound and formed metabolite are less toxic than reference UV filters (octinoxate and octocrylene). [ABSTRACT FROM AUTHOR]

Background: Unlike Transposable Elements (TEs) and gene/genome duplication, the role of the so-called nuclear plastid DNA sequences (NUPTs) in shaping the evolution of genome architecture and function remains poorly studied. We investigate here the functional and evolutionary fate of NUPTs in the orphan crop Moringa oleifera (moringa), featured by the highest fraction of plastid DNA found so far in any plant genome, focusing on (i) any potential biases in their distribution in relation to specific nuclear genomic features, (ii) their contribution to the emergence of new genes and gene regions, and (iii) their impact on the expression of target nuclear genes. Results: In agreement with their potential mutagenic effect, NUPTs are underrepresented among structural genes, although their overall transcription levels and broadness were only lower when involved exonic regions; the occurrence of plastid DNA generally did not result in a broader expression, except among those affected in introns by older NUPTs. In contrast, we found a strong enrichment of NUPTs among specific superfamilies of retrotransposons and several classes of RNA genes, including those participating in the protein biosynthetic machinery (i.e., rRNA and tRNA genes) and a specific class of regulatory RNAs. A significant fraction of NUPT RNA genes was found to be functionally expressed, thus potentially contributing to the nuclear pool. Conclusions: Our results complete our view of the molecular factors driving the evolution of nuclear genome architecture and function, and support plastid DNA in moringa as a major source of (i) genome complexity and (ii) the nuclear pool of RNA genes. [ABSTRACT FROM AUTHOR]

The purpose of current research work was to investigate the effect of mutagenesis on endoglucanase B activity of indigenous strain of Aspergillus niger and its heterologous expression studies in the pET28a+ vector. The physical and chemical mutagens were employed to incorporate mutations in A. niger. For determination of mutations, mRNA was isolated followed by cDNA synthesis and cellulase gene was amplified, purified and sequenced both from native and mutant A. niger. On comparison of gene sequences, it was observed that 5 nucleotide base pairs have been replaced in the mutant cellulase. The mutant recombinant enzyme showed 4.5 times higher activity (428.5 µmol/mL/min) as compared to activity of native enzyme (94 µmol/mL/min). The mutant gene was further investigated using Phyre2 and I-Tesser tools which exhibited 71% structural homology with Endoglucanase B of Thermoascus aurantiacus. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent accessible surface area (SASA), radius of gyration (Rg) and hydrogen bonds analysis were carried at 35°C and 50°C to explore the integrity of structure of recombinant mutant endoglucanase B which corresponded to its optimal temperature. Hydrogen bonds analysis showed more stability of recombinant mutant endoglucanase B as compared to native enzyme. Both native and mutant endoglucanase B genes were expressed in pET 28a+ and purified with nickel affinity chromatography. Theoretical masses determined through ExPaSy Protparam were found 38.7 and 38.5 kDa for native and mutant enzymes, respectively. The optimal pH and temperature values for the mutant were 5.0 and 50°C while for native these were found 4.0 and 35°C, respectively. On reacting with carboxy methyl cellulose (CMC) as substrate, the mutant enzyme exhibited less Km (0.452 mg/mL) and more Vmax (50.25 µmol/ml/min) as compared to native having 0.534 mg/mL as Km and 38.76 µmol/ml/min as Vmax. Among metal ions, Mg2+ showed maximum inducing effect (200%) on cellulase activity at 50 mM concentration followed by Ca2+ (140%) at 100 mM concentration. Hence, expression of a recombinant mutant cellulase from A. niger significantly enhanced its cellulytic potential which could be employed for further industrial applications at pilot scale. [ABSTRACT FROM AUTHOR]

Antibodies are engineerable quantities in medicine. Learning antibody molecular recognition would enable the in silico design of high affinity binders against nearly any proteinaceous surface. Yet, publicly available experiment antibody sequence-binding datasets may not contain the mutagenic, antigenic, or antibody sequence diversity necessary for deep learning approaches to capture molecular recognition. In part, this is because limited experimental platforms exist for assessing quantitative and simultaneous sequence-function relationships for multiple antibodies. Here we present MAGMA-seq, an integrated technology that combines multiple antigens and multiple antibodies and determines quantitative biophysical parameters using deep sequencing. We demonstrate MAGMA-seq on two pooled libraries comprising mutants of nine different human antibodies spanning light chain gene usage, CDR H3 length, and antigenic targets. We demonstrate the comprehensive mapping of potential antibody development pathways, sequence-binding relationships for multiple antibodies simultaneously, and identification of paratope sequence determinants for binding recognition for broadly neutralizing antibodies (bnAbs). MAGMA-seq enables rapid and scalable antibody engineering of multiple lead candidates because it can measure binding for mutants of many given parental antibodies in a single experiment. Limited experimental platforms exist for assessing quantitative sequence-function relationships for multiple antibodies. Here, authors develop a deep-sequencing based technology called MAGMA-seq, that determines the quantitative properties of antibody libraries. [ABSTRACT FROM AUTHOR]

7-Methylxanthine (7-MX, CAS No. 552-62-5, purity 99.46%) is the first orally administered drug candidate, which showed anti-myopic activity in different pre-clinical studies. In the present study, we investigated the in-vivo genotoxic and mutagenic toxicity of 7-MX in Wistar rats using comet/single-cell gel electrophoresis, chromosomal aberration and micronucleus assays after oral administration. For the single-dose study (72 h), two doses of 7-MX 300 and 2000 mg/kg body weight were selected. For a repeated dose 28 d study, three doses (250, 500, and 1000 mg/kg) of 7-MX were selected. The doses were administered via oral gavage in the suspension form. Blood and major vital organs such as bone marrow, lung and liver were used to perform comet/single cell gel electrophoresis, chromosomal aberration, and micronucleus assays. The in-vitro Ames test was performed on TA98 and TA100 strains. In the chromosomal aberration study, a non-significant increase in deformities such as stickiness, ring chromosome, and endoreduplication was observed in bone marrow cells of 7-MX treated groups. These chromosomal alterations were observed upon treatment with doses of 2000 mg/kg single dose for 72 h and 1000 mg/kg repeated dose for 28 d. At a dose of 500 mg/kg, DNA damage in terms of tail length, tail moment, % tail DNA and the olive tail moment was also found to be non-significant in 7-MX treated groups. The Ames test showed the non-mutagenic nature of 7-MX in both strains of TA98 and TA100 of Salmonella typhimurium with or without metabolic activation. Thus, the present work is interesting in view of the non- genotoxicity and non-mutagenicity of repeated doses of 7-MX. [ABSTRACT FROM AUTHOR]

Small molecules that specifically target viral polymerases—crucial enzymes governing viral genome transcription and replication—play a pivotal role in combating viral infections. Presently, approved polymerase inhibitors cover nine human viruses, spanning both DNA and RNA viruses. This review provides a comprehensive analysis of these licensed drugs, encompassing nucleoside/nucleotide inhibitors (NIs), non-nucleoside inhibitors (NNIs), and mutagenic agents. For each compound, we describe the specific targeted virus and related polymerase enzyme, the mechanism of action, and the relevant bioactivity data. This wealth of information serves as a valuable resource for researchers actively engaged in antiviral drug discovery efforts, offering a complete overview of established strategies as well as insights for shaping the development of next-generation antiviral therapeutics. [ABSTRACT FROM AUTHOR]

Mutagenesis is the process of creating mutations in an organism's DNA. Induced mutagenesis can be used to create crops with higher yields, better quality, disease and insect resistance, and stress tolerance, all of which are critical for food security and sustainable agriculture. Physical, biological and chemical mutagens can induce mutations in seeds and other plant propagules, followed by selection for superior agronomic traits in the first generation. The phenotypic stability of agronomic features generated by the mutagenesis process is established in the second and third generations, with the following generations undergoing further evaluation. Only mutant lines exhibiting the desired characteristics are chosen as new varieties or parent lines for a breeding program. New crop varieties are developed around the world utilizing induced mutagenesis techniques such as irradiation or chemical mutagens. In this review, we examine the different approaches to mutagenesis, their applications, challenges and prospects for increasing crop productivity and quality. [ABSTRACT FROM AUTHOR]

The repeated failure to treat patients chronically infected with hepatitis E (HEV) and C (HCV) viruses, despite the absence of resistance-associated substitutions (RAS), particularly in response to prolonged treatments with the mutagenic agents of HEV, suggests that quasispecies structure may play a crucial role beyond single point mutations. Quasispecies structured in a flat-like manner (referred to as flat-like) are considered to possess high average fitness, occupy a significant fraction of the functional genetic space of the virus, and exhibit a high capacity to evade specific or mutagenic treatments. In this paper, we studied HEV and HCV samples using high-depth next-generation sequencing (NGS), with indices scoring the different properties describing flat-like quasispecies. The significance of these indices was demonstrated by comparing the values obtained from these samples with those from acute infections caused by respiratory viruses (betacoronaviruses, enterovirus, respiratory syncytial viruses, and metapneumovirus). Our results revealed that flat-like quasispecies in HEV and HCV chronic infections without RAS are characterized by numerous low-frequency haplotypes with no dominant one. Surprisingly, these low-frequency haplotypes (at the nucleotide level) exhibited a high level of synonymity, resulting in much lower diversity at the phenotypic level. Currently, clinical approaches for managing flat-like quasispecies are lacking. Here, we propose methods to identifying flat-like quasispecies, which represents an essential initial step towards exploring alternative treatment protocols for viruses resistant to conventional therapies. [ABSTRACT FROM AUTHOR]

The Trojan exon method, which makes use of intronically inserted T2A-Gal4 cassettes, has been widely used in Drosophila to create thousands of gene-specific Gal4 driver lines. These dual-purpose lines provide genetic access to specific cell types based on their expression of a native gene while simultaneously mutating one allele of the gene to enable loss-of-function analysis in homozygous animals. While this dual use is often an advantage, the truncation mutations produced by Trojan exons are sometimes deleterious in heterozygotes, perhaps by creating translation products with dominant negative effects. Such mutagenic effects can cause developmental lethality as has been observed with genes encoding essential transcription factors. Given the importance of transcription factors in specifying cell type, alternative techniques for generating specific Gal4 lines that target them are required. Here, we introduce a modified Trojan exon method that retains the targeting fidelity and plug-and-play modularity of the original method but mitigates its mutagenic effects by exploiting the self-splicing capabilities of split inteins. "Split Intein Trojan exons" (siTrojans) ensure that the two truncation products generated from the interrupted allele of the native gene are trans-spliced to create a full-length native protein. We demonstrate the efficacy of siTrojans by generating a comprehensive toolkit of Gal4 and Split Gal4 lines for the segmentally expressed Hox transcription factors and illustrate their use in neural circuit mapping by targeting neurons according to their position along the anterior-posterior axis. Both the method and the Hox gene-specific toolkit introduced here should be broadly useful. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to pinpoint pathogenic genes and assess the mutagenic pathogenicity in two pediatric patients with hereditary spherocytosis. Methods: We utilized whole-exome sequencing (WES) for individual analysis (case 1) and family-based trio analysis (case 2). The significance of the intronic mutation was validated through a Minigene splicing assay and supported by subsequent in vitro experiments. Results: Both probands received a diagnosis of hereditary spherocytosis. WES identified a novel ANK1 c.1504-9G>A mutation in both patients, causing the retention of seven nucleotides at the 5' end of intron 13, as substantiated by the Minigene assay. This variant results in a premature stop codon and the production of a truncated protein. In vitro studies indicated a reduced expression of the ANK1 gene. Conclusion: The novel ANK1 c.1504-9G>A variant is established as the causative factor for hereditary spherocytosis, with the c.1504-9G site functioning as a splicing receptor. [ABSTRACT FROM AUTHOR]

At present, atmospheric and room‐temperature plasma (ARTP) is regarded as a new and powerful mutagenesis technology with the advantages of environment‐friendliness, operation under mild conditions, and fast mutagenesis speed. Compared with traditional mutagenesis strategies, ARTP is used mainly to change the structure of microbial DNA, enzymes, and proteins through a series of physical, chemical, and electromagnetic effects with the organisms, leading to nucleotide breakage, conversion or inversion, causing various DNA damages, so as to screen out the microbial mutants with better biological characteristics. As a result, in recent years, ARTP mutagenesis and the combination of ARTP with traditional mutagenesis have been widely used in microbiology, showing great potential for application. In this review, the recent progress of ARTP mutagenesis in different application fields and bottlenecks of this technology are systematically summarized, with a view to providing a theoretical basis and technical support for better application. Finally, the outlook of ARTP mutagenesis is presented, and we identify the challenges in the field of microbial mutagenesis by ARTP. Significance statement: The aim of this review is to analyze the beneficial mutagenic effects induced by ARTP on microbial cells and the related mutagenic mechanisms. Subsequently, bottleneck issues and the recent research progress of ARTP on mutagenesis are systematically summarized, and the application prospect is presented. This review may provide valuable insights and research ideas for future atmospheric and room‐temperature plasma mutagenesis of cells. [ABSTRACT FROM AUTHOR]

Strain improvement via chemical mutagen could impart traits with better enzyme production or improved characteristics. The present study sought to investigate the physicochemical properties of pullulanase produced from the wild Bacillus sp and the mutant. The pullulanases produced from the wild and the mutant Bacillus sp. (obtained via induction with ethyl methyl sulfonate) were purified in a-three step purification procedure and were also characterized. The wild and mutant pullulanases, which have molecular masses of 40 and 43.23 kDa, showed yields of 2.3% with 6.0-fold purification and 2.0% with 5.0-fold purification, respectively, and were most active at 50 and 40 °C and pH 7 and 8, respectively. The highest stability of the wild and mutant was between 40 and 50 °C after 1 h, although the mutant retained greater enzymatic activity between pH 6 and 9 than the wild. The mutant had a decreased Km of 0.03 mM as opposed to the wild type of 1.6 mM. In comparison to the wild, the mutant demonstrated a better capacity for tolerating metal ions and chelating agents. These exceptional characteristics of the mutant pullulanase may have been caused by a single mutation, which could improve its utility in industrial and commercial applications. [ABSTRACT FROM AUTHOR]

Textile industries use large amounts of water as well as dyes. These dyes containing water are then discharged into the water bodies causing a significant role in water pollution. Brilliant Green dye contributes to many harmful diseases related to the respiratory and gastrointestinal tract. In this study, Symplocos racemosa (SR) agro-waste was chemically treated with acid (SR-HCl) and base (SR-NaOH) and then used for removing Brilliant Green Dye (BGD) on the batch scale. They were characterized by SEM, EDX, FTIR, XRD, TGA and DSC. Optimized conditions were 30 °C temperature, pH 6, adsorbent dose of 0.10 g/25 ml dye solution, shaking speed of 100 revolutions per minute, initial dye concentration of 50 ppm and 35 min time for shaking adsorbent and dye solution. Adsorption data obtained were analyzed using isotherms. The experimental data was found to fit well with the Langmuir model and the maximum adsorption capacity (qmax) of BGD on the SR, SR-HCl, and SR-NaOH was revealed to be 62.90, 65.40, and 71 mg/g respectively. Kinetic data (pseudo-first-order and pseudo-second-order) were evaluated and adsorption tends to follow the pseudo-2nd-order, which indicated the chemisorption mechanism. The results revealed that Symplocos racemosa agro-waste can be considered as the potential biosorbent. [ABSTRACT FROM AUTHOR]

Histone proteins can become trapped on DNA in the presence of 5-formylcytosine (5fC) to form toxic DNA-protein conjugates. Their repair may involve proteolytic digestion resulting in DNA-peptide cross-links (DpCs). Here, we have investigated replication of a model DpC comprised of an 11-mer peptide (NH2--GGGKGLGK*GGA) containing an oxylysine residue (K*) conjugated to 5fC in DNA. Both CXG and CXT (where X = 5fC-DpC) sequence contexts were examined. Replication of both constructs gave low viability (<10%) in Escherichia coli, whereas TLS efficiency was high (72%) in HEK 293T cells. In E. coli, the DpC was bypassed largely error-free, inducing only 2 to 3% mutations, which increased to 4 to 5% with SOS. For both sequences, semi-targeted mutations were dominant, and for CXG, the predominant mutations were G→T and G→C at the 3'-base to the 5fC-DpC. In HEK 293T cells, 7 to 9% mutations occurred, and the dominant mutations were the semi-targeted G → T for CXG and T → G for CXT. These mutations were reduced drastically in cells deficient in hPol η, hPol ι or hPol ζ, suggesting a role of these TLS polymerases in mutagenic TLS. Steady-state kinetics studies using hPol η confirmed that this polymerase induces G → T and T → G transversions at the base immediately 3' to the DpC. This study reveals a unique replication pattern of 5fC-conjugated DpCs, which are bypassed largely error-free in both E. coli and human cells and induce mostly semi-targeted mutations at the 3' position to the lesion. [ABSTRACT FROM AUTHOR]

Background: We have been conducting a collaborative study on the thresholds of mutagens. In our previous examinations of cell activity and cell proliferation as endpoints, both displayed hormesis. This time, we conducted experiments to determine thresholds using the micronucleus test as an endpoint. Methods: The micronucleus test was conducted using Chinese hamster CHL/IU cells and mouse lymphoid L5178Y cells. Additionally, we conducted preliminary investigations into the gene expression using human TK6 cells. Results: When adhesive CHL/IU cells were treated with mitomycin C (MMC), and the hormetic response was examined, hormesis was not observed clearly. When L5178Y cells were treated with methyl methanesulfonate (EMS), AF-2, MMC, and colchicine, all of them exhibited an adaptive response. Additionally, cross-adaptive responses using AF-2 and MMC or EMS and MMC were conducted, both combinations showed a cross-adaptive response. When the gene expression patterns of six genes were investigated by RT-PCR after treatment with MMC, EMS, and H2O2 using TK6 cells, two genes, GADD45 A and P21, were induced in a dose- and time-dependent manner. Conclusion: Adaptive responses arise from preconditioning. As hormesis is inherently linked to preconditioning, adaptive responses observed in this study strongly suggest that hormesis was induced, hence existence of thresholds. [ABSTRACT FROM AUTHOR]

Dietary exposure to aflatoxin B1 (AFB1) is a recognized risk factor for developing hepatocellular carcinoma. The mutational signature of AFB1 is characterized by high‐frequency base substitutions, predominantly G>T transversions, in a limited subset of trinucleotide sequences. The 8,9‐dihydro‐8‐(2,6‐diamino‐4‐oxo‐3,4‐dihydropyrimid‐5‐yl‐formamido)‐9‐hydroxyaflatoxin B1 (AFB1‐FapyGua) has been implicated as the primary DNA lesion responsible for AFB1‐induced mutations. This study evaluated the mutagenic potential of AFB1‐FapyGua in four sequence contexts, including hot‐ and cold‐spot sequences as apparent in the mutational signature. Vectors containing site‐specific AFB1‐FapyGua lesions were replicated in primate cells and the products of replication were isolated and sequenced. Consistent with the role of AFB1‐FapyGua in AFB1‐induced mutagenesis, AFB1‐FapyGua was highly mutagenic in all four sequence contexts, causing G>T transversions and other base substitutions at frequencies of ~80%–90%. These data suggest that the unique mutational signature of AFB1 is not explained by sequence‐dependent fidelity of replication past AFB1‐FapyGua lesions. [ABSTRACT FROM AUTHOR]

Stevia rebaudiana Bertoni belongs to Asteraceae family and is known for production of sweet glycosides, an alternative to sugar. The impact of Ethyl Methane Sulfonate (EMS) in developing new stevia mutants was carried out at Department of Horticulture University of Agricultural Sciences, GKVK, Bengaluru. Seeds of stevia cv. CIM-Madhu were collected and exposed at different durations of 1, 3 & 6 hrat 0.1 per cent, 0.2 per cent, 0.4 per cent, 0.6 per cent, 0.8 per cent and 1.0 per cent EMS concentrations to determine the LD50 value. Germination percentage of non-mutagenized seeds was maximum (70%) which was followed by 0.1 per cent concentration of EMS with 68 per cent germination and 2.86 per cent reduction over the control. Survival percentage was 93 per cent in control which was followed by 85 per cent at 0.1 per cent of EMS. Exposure of non-mutagenized seeds took minimum days for germination. However, as the EMS concentration increases, days taken for germination tend to get longer. Treatment with a 1.0 per cent EMS concentration exhibits the most pronounced delay in germination. LD50 a dose that causes 50 per cent mortality to the seeds was found at 0.8 per cent EMS concentration. After ascertaining LD50 value in both the treatments, mutation was induced to create variability for morphological and other desirable traits. [ABSTRACT FROM AUTHOR]

Genotoxic impurities are a class of highly potent mutagenic substances that typically needs to be controlled down to low ppm level in pharmaceuticals. A novel LC-MS/MS limit test method (single impurity ≤16.7 ppm) for detecting five impurities in Posaconazole has been established and partially validated. The chromatographic separation of analytes was conducted on an YMC-Triart C18 column and gradient elution was performed with 0.1% formic acid aqueous solution and acetonitrile as mobile phase A and B, respectively. Five impurities were carried out in ESI+ and MRM with the following mass transition pairs: m/z 390.2→296.2 for BSKZ029, m/z 300.4→136.2 for BSKZ117, m/z 207.0→162.2 for BSKZ135, m/z 209.0→91.0 for BSKZ155 and m/z 499.1→258.1 for BSKZ160. The established method exhibited good specificity, well robustness and high sensitivity with the LOD and LOQ was 1.34-1.56 ng/mL and 4.01-4.69 ng/mL, respectively. The genotoxicity of these impurities were evaluated by two (Q)SAR prediction methodologies, and results showed that BSKZ135 and BSKZ029 exhibited no genotoxicity, while BSKZ155, BSKZ117 and BSKZ160 possessed potent mutagenicity risk. Furthermore, the possible action-mechanisms of which were analyzed and proposed. This study has instructive significance to the analysis and genotoxicity research of genotoxic impurities, and also provides technical support for the supervision of the drug administration. [ABSTRACT FROM AUTHOR]

The 1986 disaster at the Chornobyl Nuclear Power Plant transformed the surrounding region into the most radioactive landscape known on the planet. Whether or not this sudden environmental shift selected for species, or even individuals within a species, that are naturally more resistant to mutagen exposure remains an open question. In this study, we collected, cultured, and cryopreserved 298 wild nematode isolates from areas varying in radioactivity within the Chornobyl Exclusion Zone. We sequenced and assembled genomes de novo for 20 Oscheius tipulae strains, analyzed their genomes for evidence of recent mutation acquisition in the field, and observed no evidence of an association between mutation and radioactivity at the sites of collection. Multigenerational exposure of each of these strains to several chemical mutagens in the lab revealed that strains vary heritably in tolerance to each mutagen, but mutagen tolerance cannot be predicted based on the radiation levels at collection sites, and Chornobyl isolates were not systematically more resistant than strains from undisturbed habitats. In sum, the absence of mutational signatures does not reflect unique capacity for tolerating DNA damage. [ABSTRACT FROM AUTHOR]

Background: Mutants have had a fundamental impact upon scientific and applied genetics. They have paved the way for the molecular and genomic era, and most of today's crop plants are derived from breeding programs involving mutagenic treatments. Results: Barley (Hordeum vulgare L.) is one of the most widely grown cereals in the world and has a long history as a crop plant. Barley breeding started more than 100 years ago and large breeding programs have collected and generated a wide range of natural and induced mutants, which often were deposited in genebanks around the world. In recent years, an increased interest in genetic diversity has brought many historic mutants into focus because the collections are regarded as valuable resources for understanding the genetic control of barley biology and barley breeding. The increased interest has been fueled also by recent advances in genomic research, which provided new tools and possibilities to analyze and reveal the genetic diversity of mutant collections. Conclusion: Since detailed knowledge about phenotypic characters of the mutants is the key to success of genetic and genomic studies, we here provide a comprehensive description of mostly morphological barley mutants. The review is closely linked to the International Database for Barley Genes and Barley Genetic Stocks (bgs.nordgen.org) where further details and additional images of each mutant described in this review can be found. [ABSTRACT FROM AUTHOR]

Epipremnum aureum, commonly known as pothos, is a hardy indoor foliage ornamental crop. Mutation breeding in Golden pothos is needed to meet the demand for more valuable and highly sought-after cultivars. The present study aimed to exploit variability on various parameters viz. new leaf emergence, survival percentage, plant height, length and width of leaves. The experiment was set up using a Complete Randomized Design (CRD) with 8 treatments and 3 replications. Rooted cuttings of Golden pothos were treated with varying concentrations of Ethyl Methane Sulfonate (EMS) for 4 hours, and a control treatment was included. The results showed that all the treated cuttings with EMS delays the new leaf emergence period compared to the control. Compared to the control, the minimum number of new leaf emergences was found in EMS-treated plants. The maximum survival percentage (100%) was recorded in 0.1%, 0.5% and control treatment. The lowest plant height (15.3 cm) was observed in treatment T4 (1.5 % EMS) treated plants. However, maximum plant height was observed in the control treatment at 150 days of interval. In comparison to the control, EMS decreased the length and width of leaves at higher dosages. The minimum leaf length and width, i.e. 2.40 cm and 1.20 cm, were recorded in plants treated with EMS at 2%, while maximum length and width were observed in control and low EMS-treated plants. The study showed that ethyl methane sulfonate affected plant development characteristics and showed some dwarfness of money plants. This appears to be the first report of EMS treatment on pothos. [ABSTRACT FROM AUTHOR]

Mastering selective molecule trafficking across human cell membranes poses a formidable challenge in healthcare biotechnology while offering the prospect of breakthroughs in drug delivery, gene therapy, and diagnostic imaging. The cholera toxin B-subunit (CTB) has the potential to be a useful cargo transporter for these applications. CTB is a robust protein that is amenable to reengineering for diverse applications; however, protein redesign has mostly focused on modifications of the N- and C-termini of the protein. Exploiting the full power of rational redesign requires a detailed understanding of the contributions of the surface residues to protein stability and binding activity. Here, we employed Rosetta-based computational saturation scans on 58 surface residues of CTB, including the GM1 binding site, to analyze both ligand-bound and ligand-free structures to decipher mutational effects on protein stability and GM1 affinity. Complimentary experimental results from differential scanning fluorimetry and isothermal titration calorimetry provided melting temperatures and GM1 binding affinities for 40 alanine mutants among these positions. The results showed that CTB can accommodate diverse mutations while maintaining its stability and ligand binding affinity. These mutations could potentially allow modification of the oligosaccharide binding specificity to change its cellular targeting, alter the B-subunit intracellular routing, or impact its shelf-life and in vivo half-life through changes to protein stability. We anticipate that the mutational space maps presented here will serve as a cornerstone for future CTB redesigns, paving the way for the development of innovative biotechnological tools. [ABSTRACT FROM AUTHOR]

Background: Zingiber zerumbet (L.) Smith (lempoyang) has a traditional application in the treatment of indigestion, worm infestation, loss of appetite, and postpartum conditions. Objectives: Extracts of Z. zerumbet (methanol, hexane, and ethyl acetate) were utilized to investigate the mutagenic, anti-mutagenic, and cytotoxic properties. Materials and Methods: Initially, a mutagenicity test (Ames test) was conducted, followed by an anti-mutagenicity test, to assess the potential of Z. zerumbet extracts in inhibiting mutagenicity induced by sodium azide and 9-aminoacridine. Furthermore, the cytotoxic ability of the extracts was evaluated using the methyl thiazolyl tetrazolium (MTT) assay. Results: The mutagenicity assessment revealed that the methanol extract of Z. zerumbet exhibited a twofold increase in the number of revertants in Salmonella typhimurium strain TA 1537. Similar results were observed for the hexane extract, except at a concentration of 6.25 mg/mL, where no significant increase in revertants was observed. On the other hand, the ethyl acetate extract demonstrated a twofold increase in revertants in S. typhimurium strain TA 1535. Notably, the ethyl acetate extract displayed remarkable anti-mutagenic activity against 9-aminoacridine, while the hexane extract exhibited strong anti-mutagenic activity against sodium azide. Regarding cytotoxicity assessment using the MTT assay, the methanol extract of Z. zerumbet exhibited the highest cytotoxicity with an IC50 value estimated at 388.50 ± 135.75 µg/mL. The hexane and ethyl acetate extracts showed IC50 values of 514.17 ± 135.75 and 589.67 ± 241.67 µg/mL, respectively. Conclusion: The extracts displayed both mutagenic and cytotoxic activities. However, they also exhibited promising anti-mutagenic potential, which could be harnessed for cancer prevention purposes. [ABSTRACT FROM AUTHOR]

The goal of this study was to perform systematic review (SR) to investigate the scientific literature regarding the genotoxicity effects of fluoride exposure (FE). The search of databases used for this study was PubMed/Medline, SCOPUS and Web of Science. The quality of included studies was assessed using the EPHPP (Effective Public Health Practice Project). A total of 20 potentially relevant studies were selected for evaluating the genotoxicity induced by fluoride. Few studies have revealed that FE induces genotoxicity. A total of 14 studies demonstrated negative results whereas 6 studies did not. After reviewing the twenty studies, 1 was classified as weak, 10 were considered moderate and 9 were considered strong, according to the EPHPP. Taken together, it has been established that genotoxicity of fluoride is limited. [ABSTRACT FROM AUTHOR]

Using the method of dominant lethal mutations, we assessed the frequency of the death of Drosophila melanogaster embryos under combined exposure to ionizing γ-radiation and non-ionizing pulsed magnetic field at various doses and modes of exposure. Mutagenic effect of combined exposure is antagonistic in nature. The antagonism is more pronounced when the following mode of exposure was used: exposure to non-ionizing pulsed magnetic field for 5 h followed by exposure to γ-radiation at doses of 3, 10, and 60 Gy. In case of reverse sequence of exposures, the antagonistic effect was statistically significant after exposure to γ-radiation at doses of 3 and 10 Gy, whereas at a dose of 20 Gy, a synergistic interaction was noted. [ABSTRACT FROM AUTHOR]

Malachite green (MG) is a synthetic cationic dye extensively utilized in the textile industry for colouring purposes. It is a mutagenic agent and potentially carcinogenic for living organisms in nature. Therefore, it is necessary to treat and discharge the industrial effluents covering MG to avoid irreversible and serious effects on both living organisms and the environment. The photocatalyst SnO2 was synthesized by a new method by complexation of sodium diethyldithiocarbamate with tin dichloride pentahydrate, followed by calcination at 450, 600 and 750°C and utilized for photocatalytic degradation of MG dye. The better degradation was obtained at calcination temperature 600°C. The fluorescent light exposure resulted better degradation % of MG dye within 20 min, and the absorbance measurements were noted after every 5 min. The degradation of MG dye improved with an increase in the dose of SnO2 photocatalyst up to 20 mg. The highest decomposition of MG dye was found at 10 pH which may be due to deprotonation. The effects of Na+, HCO3−, Ca2+, Cl−, K+, SO42− and Mg2+ on dye degradation were examined and results showed that the salts had no effect on degradation. The kinetics and isothermic studies were carried out where the kinetic model pseudo-second-order and Langmuir isotherm were highly fitted. The factorial design was also drawn to checked the combined effects of variables, such as pH, dose, concentration and irradiation time on the degradation of MG dye. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an endocrine-disrupting compound and a mutagenic agent that poses health hazards to living organisms, making it a global contaminant. Several remediation techniques have been reported in the literature, however, a mixed-method science mapping analysis of research trends on BPA is still lacking. The present study aimed to investigate global research trends in BPA remediation. Published research papers on BPA remediation indexed in Web of Science, PubMed, and Scopus between 1992 and 2021 were analysed qualitatively and quantitatively using science mapping algorithms including Rstudio, bibliometrix package and R Version 4.2.1. The thematic areas were determined using k-means clustering of the author-keywords while Porter's stemming algorithm was used to stemmed inflectional terms to their roots. Overall, 640 documents were published by 1903 authors with 2.07 authors/article and 0.336 article/author, 4.31 co-authors/article, an annual growth rate of 17.35% and a collaboration index of 2.99. Research productivity increased from 1 article in 1992 to 93 articles in 2021. The citations of the topmost 23 articles ranged from 365 to 109 and the total citation per year ranged from 45.6 to 27.3. China (n = 267, 41.7%), Japan (n = 53, 8.3%), USA (n = 33, 5.2%) and Korea (n = 28, 4.4%) were respectively the top four countries based on the total of published articles and overall citation. There were 48 relevant keywords dominated by Bisphenol A, adsorption, biodegradation, and peroximonosulphate. The present analysis identifies research accomplishment, focus and gaps on Bisphenol A remediation and offer the researchers the information needed to forecast future research priorities that can help policymakers and governments to internationalize collaborations and create research curricula that can remediate BPA on a global scale. [ABSTRACT FROM AUTHOR]