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1.
PLoS One ; 15(5): e0232775, 2020.
Article in English | MEDLINE | ID: mdl-32374766

ABSTRACT

Antibacterial photodynamic therapy (aPDT) and antibacterial blue light (aBL) are emerging treatment methods auxiliary to mechanical debridement for periodontitis. APDT provided with near-infrared (NIR) light in conjunction with an indocyanine green (ICG) photosensitizer has shown efficacy in several dental in-office-treatment protocols. In this study, we tested Streptococcus mutans biofilm sensitivity to either aPDT, aBL or their combination dual-light aPDT (simultaneous aPDT and aBL) exposure. Biofilm was cultured by pipetting diluted Streptococcus mutans suspension with growth medium on the bottom of well plates. Either aPDT (810 nm) or aBL (405 nm) or a dual-light aPDT (simultaneous 810 nm aPDT and 405 nm aBL) was applied with an ICG photosensitizer in cases of aPDT or dual-light, while keeping the total given radiant exposure constant at 100 J/cm2. Single-dose light exposures were given after one-day or four-day biofilm incubations. Also, a model of daily treatment was provided by repeating the same light dose daily on four-day and fourteen-day biofilm incubations. Finally, the antibacterial action of the dual-light aPDT with different energy ratios of 810 nm and 405 nm of light were examined on the single-day and four-day biofilm protocols. At the end of each experiment the bacterial viability was assessed by colony-forming unit method. Separate samples were prepared for confocal 3D biofilm imaging. On a one-day biofilm, the dual-light aPDT was significantly more efficient than aBL or aPDT, although all modalities were bactericidal. On a four-day biofilm, a single exposure of aPDT or dual-light aPDT was more efficient than aBL, resulting in a four logarithmic scale reduction in bacterial counts. Surprisingly, when the same amount of aPDT was repeated daily on a four-day or a fourteen-day biofilm, bacterial viability improved significantly. A similar improvement in bacterial viability was observed after repetitive aBL application. This viability improvement was eliminated when dual-light aPDT was applied. By changing the 405 nm to 810 nm radiant exposure ratio in dual-light aPDT, the increase in aBL improved the antibacterial action when the biofilm was older. In conclusion, when aPDT is administered repeatedly to S. mutans biofilm, a single wavelength-based aBL or aPDT leads to a significant biofilm adaptation and increased S. mutans viability. The combined use of aBL light in synchrony with aPDT arrests the adaptation and provides significantly improved and sustained antibacterial efficacy.


Subject(s)
Adaptation, Biological/drug effects , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Indocyanine Green/pharmacology , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Streptococcus mutans/drug effects , Adaptation, Biological/radiation effects , Bacterial Load/drug effects , Bacterial Load/radiation effects , Biofilms/radiation effects , Humans , Microbial Viability/drug effects , Microbial Viability/radiation effects , Oral Hygiene/methods , Periodontitis/drug therapy , Streptococcus mutans/radiation effects
2.
J Clin Endocrinol Metab ; 105(5)2020 05 01.
Article in English | MEDLINE | ID: mdl-32115644

ABSTRACT

CONTEXT: Normal vitamin D homeostasis is necessary to ensure optimal mineral metabolism. Dietary insufficiency of vitamin D and the lack of sunlight each have well understood roles in vitamin D deficiency; however, the extent to which common genetic variations in vitamin D metabolizing enzymes contribute to alterations in vitamin D homeostasis remains uncertain. OBJECTIVE: To examine the possibility that common coding variation in vitamin D metabolizing enzymes alters vitamin D homeostasis we determined the effect of 44 nonsynonymous polymorphisms in CYP2R1, the vitamin D 25-hydroxylase, on enzyme function. RESULTS: Twenty-one of these polymorphisms decreased activity, while 2 variants increased activity. The frequency of CYP2R1 alleles with decreased 25-hydroxylase activity is 3 in every 1000 Caucasians and 7 in every 1000 African Americans. In populations where exposure to sunlight is high, alleles with decreased function occur at a frequency as high as 8%. The pattern of selected variation as compared to nonselected variation is consistent with it being the result of positive selection for nonfunctional alleles closer to the equator. To examine this possibility, we examined the variation pattern in another protein in the vitamin D pathway, the vitamin D binding protein (GC protein). The pattern of selected variation in the GC protein as compared to nonselected variation is also consistent with it being the result of positive selection for nonfunctional alleles closer to the equator. CONCLUSIONS: CYP2R1 polymorphisms have important effects on vitamin D homeostasis, and the geographic variability of CYP2R1 alleles represents an adaptation to differential exposures to UVB irradiation from sunlight.


Subject(s)
Cholestanetriol 26-Monooxygenase/genetics , Cytochrome P450 Family 2/genetics , Gene Frequency , Selection, Genetic , Vitamin D/metabolism , Adaptation, Biological/genetics , Adaptation, Biological/radiation effects , Amino Acid Substitution/genetics , Genetic Predisposition to Disease , Genetics, Population , Geography , HEK293 Cells , Homeostasis/genetics , Humans , Metabolic Networks and Pathways/genetics , Polymorphism, Single Nucleotide , Skin Pigmentation/genetics , Ultraviolet Rays , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/genetics , Vitamin D Deficiency/metabolism
3.
Int J Radiat Biol ; 96(5): 561-576, 2020 05.
Article in English | MEDLINE | ID: mdl-31976798

ABSTRACT

Purpose: Various sources of radiation including radiofrequency, electromagnetic radiation (EMR), low- dose X-radiation, low-level microwave radiation and ionizing radiation (IR) are indispensable parts of modern life. In the current review, we discussed the adaptive responses of biological systems to radiation with a focus on the impacts of radiation-induced oxidative stress (RIOS) and its molecular downstream signaling pathways.Materials and methods: A comprehensive search was conducted in Web of Sciences, PubMed, Scopus, Google Scholar, Embase, and Cochrane Library. Keywords included Mesh terms of "radiation," "electromagnetic radiation," "adaptive immunity," "oxidative stress," and "immune checkpoints." Manuscripts published up until December 2019 were included.Results: RIOS induces various molecular adaptors connected with adaptive responses in radiation exposed cells. One of these adaptors includes p53 which promotes various cellular signaling pathways. RIOS also activates the intrinsic apoptotic pathway by depolarization of the mitochondrial membrane potential and activating the caspase apoptotic cascade. RIOS is also involved in radiation-induced proliferative responses through interaction with mitogen-activated protein kinases (MAPks) including p38 MAPK, ERK, and c-Jun N-terminal kinase (JNK). Protein kinase B (Akt)/phosphoinositide 3-kinase (PI3K) signaling pathway has also been reported to be involved in RIOS-induced proliferative responses. Furthermore, RIOS promotes genetic instability by introducing DNA structural and epigenetic alterations, as well as attenuating DNA repair mechanisms. Inflammatory transcription factors including macrophage migration inhibitory factor (MIF), nuclear factor κB (NF-κB), and signal transducer and activator of transcription-3 (STAT-3) paly major role in RIOS-induced inflammation.Conclusion: In conclusion, RIOS considerably contributes to radiation induced adaptive responses. Other possible molecular adaptors modulating RIOS-induced responses are yet to be divulged in future studies.


Subject(s)
Adaptation, Biological/radiation effects , Oxidative Stress/radiation effects , AMP-Activated Protein Kinases/physiology , Animals , Autophagy/physiology , Autophagy-Related Proteins/physiology , Beclin-1/physiology , Cysteine Endopeptidases/physiology , Humans , Kelch-Like ECH-Associated Protein 1/physiology , NF-E2-Related Factor 2/physiology , NF-kappa B/physiology , Oxidative Stress/physiology , Signal Transduction/physiology
4.
Int J Mol Sci ; 20(20)2019 Oct 09.
Article in English | MEDLINE | ID: mdl-31601021

ABSTRACT

Cichlid fishes are the subject of scientific interest because of their rapid adaptive radiation, resulting in extensive ecological and taxonomic diversity. In this study, we examined 11 morphologically distinct cichlid species endemic to Barombi Mbo, the largest crater lake in western Cameroon, namely Konia eisentrauti, Konia dikume, Myaka myaka, Pungu maclareni, Sarotherodon steinbachi, Sarotherodon lohbergeri, Sarotherodon linnellii, Sarotherodon caroli, Stomatepia mariae, Stomatepia pindu, and Stomatepia mongo. These species supposedly evolved via sympatric ecological speciation from a common ancestor, which colonized the lake no earlier than one million years ago. Here we present the first comparative cytogenetic analysis of cichlid species from Barombi Mbo Lake using both conventional (Giemsa staining, C-banding, and CMA3/DAPI staining) and molecular (fluorescence in situ hybridization with telomeric, 5S, and 28S rDNA probes) methods. We observed stability on both macro and micro-chromosomal levels. The diploid chromosome number was 2n = 44, and the karyotype was invariably composed of three pairs of meta/submetacentric and 19 pairs of subtelo/acrocentric chromosomes in all analysed species, with the same numbers of rDNA clusters and distribution of heterochromatin. The results suggest the evolutionary stability of chromosomal set; therefore, the large-scale chromosomal rearrangements seem to be unlikely associated with the sympatric speciation in Barombi Mbo.


Subject(s)
Adaptation, Biological/genetics , Adaptation, Biological/radiation effects , Chromosomal Instability/radiation effects , Cichlids/genetics , Animals , Biological Evolution , Cameroon , Chromosome Banding , Chromosome Mapping , In Situ Hybridization, Fluorescence , Karyotype , Karyotyping , Lakes , Telomere/genetics
5.
Trends Cancer ; 5(6): 365-390, 2019 06.
Article in English | MEDLINE | ID: mdl-31208698

ABSTRACT

Most Phase II and III clinical trials in head and neck cancer (HNC) combine two or more treatment modalities, which are based, in part, on knowledge of the molecular mechanisms of innate and acquired resistance to monotherapy. In this review, we describe the range of tumor-cell autonomously derived (intrinsic) and tumor-microenvironment-derived (extrinsic) acquired-resistance mechanisms to various FDA-approved monotherapies for HNC. Specifically, we describe how tumor cells and the tumor microenvironment (TME) respond to radiation, chemotherapy, targeted therapy (cetuximab), and immunotherapies [programmed cell death 1 (PD-1) inhibitors] and adapt to the selective pressure of these monotherapies. Due to the diversity of adaptive responses to monotherapy, monitoring the response to treatment in patients is critical to understand the path that leads to resistance and to guide the optimal therapeutic drug combinations in the clinical setting. We envisage that applying such a rationale-based therapeutic strategy will improve treatment efficacy in HNC patients.


Subject(s)
Adaptation, Biological , Head and Neck Neoplasms/therapy , Adaptation, Biological/drug effects , Adaptation, Biological/radiation effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor , Clinical Trials as Topic , Drug Resistance, Neoplasm , Head and Neck Neoplasms/etiology , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Humans , Immunotherapy , Molecular Targeted Therapy , Radiation Tolerance , Radiotherapy , Signal Transduction , Treatment Outcome , Tumor Microenvironment/drug effects , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Tumor Microenvironment/radiation effects
6.
Plant Physiol Biochem ; 137: 162-168, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30784988

ABSTRACT

This research analysed the growth process dynamics of soft wheat (Triticum aestivum L.) seeds cultivated in contrasting microclimatic conditions. We used acute gamma irradiation (5-50 Gy) as a provocative factor to detect hidden differences in the adaptive potential of seeds cultivated under adverse conditions (wet and cool field season) in comparison to seeds obtained under controlled conditions (hydroponic greenhouse). Seeds harvested from wheat plants cultivated in challenging field conditions demonstrated lower weight; moreover, their offspring also had a lower weight and seedling survival rate, as well as a delay in the formation of the fourth - sixth roots. The discrepancy in growth characteristics increased from the beginning to the end of the experiments and was particularly pronounced in offspring cultivated under adverse conditions throughout the entire experiment. The offspring of control seeds were more radioresistant than their field seed counterparts. At the same time, the "field" seeds were characterised by stimulation of growth and development of seedlings in their responses to irradiation. Few seedlings grown from "greenhouse" seeds exhibited evidence of root necrosis and twisted roots. Among the field plants, unusual developmental anomalies for 'greenhouse' seeds were encountered, including the disruption of gravitropism, thickening of roots, changes in the form of coleoptiles and leaves, and necrotic coleoptiles. Gamma irradiation stimulated an increase in the number of seedlings with various developmental disorders. In the case of seed progeny grown under adverse conditions, developmental anomalies were more frequent following irradiation relative to optimal conditions.


Subject(s)
Seeds/genetics , Seeds/radiation effects , Triticum/genetics , Triticum/radiation effects , Adaptation, Biological/genetics , Adaptation, Biological/radiation effects , Gamma Rays , Microclimate , Radiation Tolerance/genetics , Seedlings/genetics , Seedlings/growth & development , Seedlings/radiation effects
7.
Nat Commun ; 9(1): 3159, 2018 08 08.
Article in English | MEDLINE | ID: mdl-30089797

ABSTRACT

Lake Tanganyika is the oldest and phenotypically most diverse of the three East African cichlid fish adaptive radiations. It is also the cradle for the younger parallel haplochromine cichlid radiations in Lakes Malawi and Victoria. Despite its evolutionary significance, the relationships among the main Lake Tanganyika lineages remained unresolved, as did the general timescale of cichlid evolution. Here, we disentangle the deep phylogenetic structure of the Lake Tanganyika radiation using anchored phylogenomics and uncover hybridization at its base, as well as early in the haplochromine radiation. This suggests that hybridization might have facilitated these speciation bursts. Time-calibrated trees support that the radiation of Tanganyika cichlids coincided with lake formation and that Gondwanan vicariance concurred with the earliest splits in the cichlid family tree. Genes linked to key innovations show signals of introgression or positive selection following colonization of lake habitats and species' dietary adaptations are revealed as major drivers of colour vision evolution. These findings shed light onto the processes shaping the evolution of adaptive radiations.


Subject(s)
Cichlids/classification , Cichlids/genetics , Evolution, Molecular , Hybridization, Genetic/radiation effects , Phylogeny , Adaptation, Biological/radiation effects , Africa, Eastern , Animals , Biodiversity , DNA, Mitochondrial/genetics , Diet , Fossils , Fresh Water , Gene Flow/radiation effects , Genetic Markers , Genotype , Geological Phenomena , Lakes , Models, Genetic , Phenotype , Sequence Alignment , Sequence Analysis, DNA , Species Specificity , Tanzania
8.
J Biosci Bioeng ; 126(5): 596-602, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29907527

ABSTRACT

Photoinhibition, or cell damage caused by excessively intense light is a major issue for the industrial use of cyanobacteria. To investigate the mechanism of responses to extreme high light intensity, gene expression analysis was performed using the model cyanobacterium Synechocystis sp. PCC 6803 (PCC 6803) cultured under various light intensities. The culture profile data demonstrated that, in contrast to the slow cell growth observed under low light intensities (30 and 50 µmol m-2 s-1), maximal cell growth was observed under mid light conditions (300 and 1000 µmol m-2 s-1). PCC 6803 cells exhibited photoinhibition when cultured under excessive high light intensities of 1100 and 1300 µmol m-2 s-1. From the low to the mid light conditions, the expression of genes related to light harvesting systems was repressed, whereas that of CO2 fixation and of D1 protein turnover-related genes was induced. Gene expression data also revealed that the down-regulation of genes related to flagellum synthesis (pilA2), pyridine nucleotide transhydrogenase (pntA and pntB), and sigma factor (sigA and sigF) represents the key responses of PCC 6803 under excessive high light conditions. The results obtained in this study provide further understanding of high light tolerance mechanisms and should help to improve the productivity of bioprocess using cyanobacteria.


Subject(s)
Adaptation, Biological , Light , Synechocystis/genetics , Synechocystis/metabolism , Synechocystis/radiation effects , Adaptation, Biological/genetics , Adaptation, Biological/radiation effects , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Cyanobacteria/genetics , Cyanobacteria/growth & development , Cyanobacteria/metabolism , Cyanobacteria/radiation effects , Gene Expression Profiling , Gene Expression Regulation, Bacterial/radiation effects , Sigma Factor/genetics , Synechocystis/growth & development
9.
Mutagenesis ; 32(2): 267-273, 2017 03 01.
Article in English | MEDLINE | ID: mdl-27831478

ABSTRACT

The present study investigates whether the chronic low-dose radiation exposure induces an in vivo radio-adaptive response in individuals from high-level natural radiation areas (HLNRA) of the Kerala coast. Peripheral blood samples from 54 adult male individuals aged between 26 and 65 years were collected for the study with written informed consent. Each of the whole blood sample was divided into three, one was sham irradiated, second and third was exposed to challenging doses of 1.0 and 2.0 Gy gamma radiation, respectively. Cytokinesis-block micronucleus (CBMN) assay was employed to study the radio-adaptive response. Seventeen individuals were from normal-level natural radiation area (NLNRA ≤1.5 mGy/year) and 37 from HLNRA (> 1.5 mGy/year). Based on the annual dose received, individuals from HLNRA were further classified into low-dose group (LDG, 1.51-5.0 mGy/year, N = 19) and high-dose group (HDG >5.0 mGy/year, N = 18). Basal frequency of micronucleus (MN) was comparable across the three dose groups (NLNRA, LDG and HDG, P = 0.64). Age of the individuals showed a significant effect on the frequency of MN after challenging dose exposures. The mean frequency of MN was significantly lower in elder (>40 years) individuals from HDG of HLNRA as compared to the young (≤40 years) individuals after 1.0 Gy (P < 0.001) and 2.0 Gy (P = 0.002) of challenging doses. However, young and elder individuals within NLNRA and LDG of HLNRA showed similar frequency of MN after the challenging dose exposures. Thus, increased level of chronic low-dose radiation (>5.0 mGy/year) seems to act as a priming dose resulting in the induction of an in vivo radio-adaptive response in elder individuals of the Kerala coast.


Subject(s)
Adaptation, Biological/radiation effects , Background Radiation , Gamma Rays , Lymphocytes/radiation effects , Micronuclei, Chromosome-Defective , Adult , Age Factors , Aged , Humans , Male , Micronucleus Tests , Middle Aged
10.
Naturwissenschaften ; 103(9-10): 71, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27542091

ABSTRACT

Microorganisms have shaped the evolution of a variety of defense mechanisms against pathogenic infections. Radioactivity modifies bacterial communities and, therefore, bird hosts breeding in contaminated areas are expected to adapt to the new bacterial environment. We tested this hypothesis in populations of barn swallows (Hirundo rustica) from a gradient of background radiation levels at Chernobyl and uncontaminated controls from Denmark. Investment in defenses against keratinolytic bacteria was measured from feather structure (i.e., susceptibility to degradation) and uropygial secretions. We studied degradability of tail feathers from areas varying in contamination in laboratory experiments using incubation of feathers with a feather-degrading bacterium, Bacillus licheniformis, followed by measurement of the amount of keratin digested. The size of uropygial glands and secretion amounts were quantified, followed by antimicrobial tests against B. licheniformis and quantification of wear of feathers. Feathers of males, but not of females, from highly contaminated areas degraded at a lower rate than those from medium and low contamination areas. However, feathers of both sexes from the Danish populations showed little evidence of degradation. Individual barn swallows from the more contaminated areas of Ukraine produced the largest uropygial secretions with higher antimicrobial activity, although wear of feathers did not differ among males from different populations. In Denmark, swallows produced smaller quantities of uropygial secretion with lower antimicrobial activity, which was similar to swallow populations from uncontaminated areas in Ukraine. Therefore, barn swallows breeding in contaminated areas invested more in all defenses against keratinolytic bacteria than in uncontaminated areas of Ukraine and Denmark, although they had similar levels of feather wear. Strong natural selection exerted by radioactivity may have selected for individuals with higher defense capacity against bacterial infections during the 30 years since the Chernobyl disaster.


Subject(s)
Adaptation, Biological/radiation effects , Environmental Exposure , Exocrine Glands/metabolism , Feathers/microbiology , Swallows/microbiology , Animals , Bacillus licheniformis/metabolism , Bodily Secretions/metabolism , Chernobyl Nuclear Accident , Denmark , Feathers/pathology , Female , Keratins/metabolism , Male , Selection, Genetic/radiation effects , Sex Factors , Ukraine
11.
Antioxid Redox Signal ; 25(2): 89-107, 2016 07 10.
Article in English | MEDLINE | ID: mdl-27021152

ABSTRACT

AIMS: Tumor hypoxia is a major biological factor causing poor patient outcome. Evidence is increasing that improved protection against reactive oxygen species (ROS) participates in therapy resistance of chronically hypoxic cancer cells. We aimed at characterizing the relevance of improved ROS defense for radiation resistance of cancer cells with tolerance to cycling anoxia/re-oxygenation stress ("anoxia-tolerant") and at designing rational treatment strategies for overcoming the resulting therapy resistance by targeting the underlying mechanisms identified in an in vitro model. RESULTS: We demonstrate that chronic exposure of NCH-H460 lung adenocarcinoma, DU145 prostate cancer, and T98G glioblastoma cells to cycling anoxia/re-oxygenation stress induced upregulation of the aspartate-aminotransferase glutamic-oxaloacetic transaminase (GOT1), particularly in RAS-driven anoxia-tolerant NCI-H460 cells. Altered glutamine utilization of the anoxia-tolerant cancer cells contributed to the observed decrease in cellular ROS levels, the increase in cellular glutathione levels, and improved cell survival on ROS-inducing treatments, including exposure to ionizing radiation. Importantly, targeting glutamine-dependent antioxidant capacity or glutathione metabolism allowed us to hit anoxia-tolerant cancer cells and to overcome their increased resistance to radiation-induced cell death. Targeting glutathione metabolism by Piperlongumine also improved the radiation response of anoxia-tolerant NCI-H460 cells in vivo. INNOVATION: Improved antioxidant capacity downstream of up-regulated GOT1-expression is a characteristic of anoxia-tolerant cancer cells and is predictive for a specific vulnerability to inhibition of glutamine utilization or glutathione metabolism, respectively. CONCLUSION: Unraveling the molecular alterations underlying improved ROS defense of anoxia-tolerant cancer cells allows the design of rational strategies for overcoming radiation resistance caused by tumor cell heterogeneity in hypoxic tumors. Antioxid. Redox Signal. 25, 89-107.


Subject(s)
Glutamine/metabolism , Glutathione/metabolism , Hypoxia/metabolism , Adaptation, Biological/genetics , Adaptation, Biological/radiation effects , Animals , Antioxidants/metabolism , Aspartate Aminotransferase, Cytoplasmic/genetics , Aspartate Aminotransferase, Cytoplasmic/metabolism , Cell Death , Cell Hypoxia , Cell Line, Tumor , Dioxolanes/pharmacology , Gene Expression Regulation, Neoplastic/radiation effects , Humans , Hypoxia/genetics , Mice , Oxidation-Reduction , Oxidative Stress/genetics , Oxidative Stress/radiation effects , Radiation Tolerance/genetics , Radiation, Ionizing , Radiation-Sensitizing Agents/pharmacology , Reactive Oxygen Species/metabolism , Xenograft Model Antitumor Assays
12.
PLoS One ; 10(3): e0121289, 2015.
Article in English | MEDLINE | ID: mdl-25807079

ABSTRACT

To observe the adaptive response (AR) induced by ionizing radiation in human fibroblasts under monolayer and 3-dimensional (3-D) condition. Three kinds of fibroblasts were cultured under both monolayer and 3-D condition. Immunofluorescent staining was used to detect the γ-H2AX foci and the morphological texture. Trypan blue staining was used to detect the cell death. Western blot was used to detect the expressions of γ-H2AX, p53 and CDKN1A/p21 (p21). We found that DNA damage increased in a dose-dependent and time-dependent manner after high doses of radiation. When cells were pretreated with a priming low dose of radiation followed by high dose radiation, DNA damage was attenuated under both monolayer and 3-D condition, and the adaptive response (AR) was induced. Additionally, the morphology of cells under monolayer and 3-D conditions were different, and radiation also induced AR according to morphological texture analysis. Priming low dose radiation induced AR both under monolayer and 3-D condition. Interestingly, 3-D microenvironment made cells more sensitive to radiation. The expression of p53 and p21 was changed and indicated that they might participate in the regulation of AR.


Subject(s)
Adaptation, Biological/radiation effects , Fibroblasts/metabolism , Fibroblasts/radiation effects , Cell Death/radiation effects , Cells, Cultured , Cyclin-Dependent Kinase Inhibitor p21/metabolism , DNA Damage/radiation effects , Dose-Response Relationship, Radiation , Histones/metabolism , Humans , Radiation, Ionizing , Tumor Suppressor Protein p53/metabolism
13.
PLoS One ; 9(4): e93371, 2014.
Article in English | MEDLINE | ID: mdl-24705271

ABSTRACT

Pirins are cupin-fold proteins, implicated in apoptosis and cellular stress in eukaryotic organisms. Pirin1 (PRN1) plays a role in seed germination and transcription of a light- and ABA-regulated gene under specific conditions in the model plant system Arabidopsis thaliana. Herein, we describe that PRN1 possesses previously unreported functions that can profoundly affect early growth, development, and stress responses. In vitro-translated PRN1 possesses quercetinase activity. When PRN1 was incubated with G-protein-α subunit (GPA1) in the inactive conformation (GDP-bound), quercetinase activity was observed. Quercetinase activity was not observed when PRN1 was incubated with GPA1 in the active form (GTP-bound). Dark-grown prn1 mutant seedlings produced more quercetin after UV (317 nm) induction, compared to levels observed in wild type (WT) seedlings. prn1 mutant seedlings survived a dose of high-energy UV (254 nm) radiation that killed WT seedlings. prn1 mutant seedlings grown for 3 days in continuous white light display disoriented hypocotyl growth compared to WT, but hypocotyls of dark-grown prn1 seedlings appeared like WT. prn1 mutant seedlings transformed with GFP constructs containing the native PRN1 promoter and full ORF (PRN1::PRN1-GFP) were restored to WT responses, in that they did not survive UV (254 nm), and there was no significant hypocotyl disorientation in response to white light. prn1 mutants transformed with PRN1::PRN1-GFP were observed by confocal microscopy, where expression in the cotyledon epidermis was largely localized to the nucleus, adjacent to the nucleus, and diffuse and punctate expression occurred within some cells. WT seedlings transformed with the 35S::PRN1-GFP construct exhibited widespread expression in the epidermis of the cotyledon, also with localization in the nucleus. PRN1 may play a critical role in cellular quercetin levels and influence light- or hormonal-directed early development.


Subject(s)
Adaptation, Biological , Arabidopsis Proteins/physiology , Arabidopsis , Carrier Proteins/physiology , Light , Quercetin/metabolism , Seeds/growth & development , Adaptation, Biological/genetics , Adaptation, Biological/radiation effects , Arabidopsis/genetics , Arabidopsis/growth & development , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Carrier Proteins/metabolism , Dioxygenases/genetics , Dioxygenases/metabolism , Germination/genetics , Intracellular Signaling Peptides and Proteins , Plants, Genetically Modified , Seedlings/genetics , Seedlings/growth & development , Seeds/genetics , Ultraviolet Rays
14.
BMC Genomics ; 15: 161, 2014 Feb 26.
Article in English | MEDLINE | ID: mdl-24571567

ABSTRACT

BACKGROUND: Gene duplication is a source of evolutionary innovation and can contribute to the divergence of lineages; however, the relative importance of this process remains to be determined. The explosive divergence of the African cichlid adaptive radiations provides both a model for studying the general role of gene duplication in the divergence of lineages and also an exciting foray into the identification of genomic features that underlie the dramatic phenotypic and ecological diversification in this particular lineage. We present the first genome-wide study of gene duplication in African cichlid fishes, identifying gene duplicates in three species belonging to the Lake Malawi adaptive radiation (Metriaclima estherae, Protomelas similis, Rhamphochromis "chilingali") and one closely related species from a non-radiated riverine lineage (Astatotilapia tweddlei). RESULTS: Using Astatotilapia burtoni as reference, microarray comparative genomic hybridization analysis of 5689 genes reveals 134 duplicated genes among the four cichlid species tested. Between 51 and 55 genes were identified as duplicated in each of the three species from the Lake Malawi radiation, representing a 38%-49% increase in number of duplicated genes relative to the non-radiated lineage (37 genes). Duplicated genes include several that are involved in immune response, ATP metabolism and detoxification. CONCLUSIONS: These results contribute to our understanding of the abundance and type of gene duplicates present in cichlid fish lineages. The duplicated genes identified in this study provide candidates for the analysis of functional relevance with regard to phenotype and divergence. Comparative sequence analysis of gene duplicates can address the role of positive selection and adaptive evolution by gene duplication, while further study across the phylogenetic range of cichlid radiations (and more generally in other adaptive radiations) will determine whether the patterns of gene duplication seen in this study consistently accompany rapid radiation.


Subject(s)
Adaptation, Biological/genetics , Adaptation, Biological/radiation effects , Cichlids/genetics , Gene Duplication , Animals , Comparative Genomic Hybridization , Evolution, Molecular , Gene Dosage , Reproducibility of Results
15.
Article in English | MEDLINE | ID: mdl-24440802

ABSTRACT

Low doses of ionizing radiation may induce an adaptive mechanism which protects embryonic stem cells against higher doses, a phenomenon which was reported previously for somatic cells. In this study, a possible adaptive response (AR) was evaluated by measuring cell survival (MTT assay) and chromosomal aberrations (micronucleus assay). Thymidine-synchronized mouse embryonic stem cells (mESCs) were exposed to 2.5, 3.7, or 5cGy (60)Co γ-rays and, after 5h challenged by a dose of 150cGy. mESCs pre-irradiated at 2.5cGy showed an adaptive response.


Subject(s)
Adaptation, Biological , Embryonic Stem Cells/radiation effects , Gamma Rays/adverse effects , Adaptation, Biological/radiation effects , Animals , Cell Survival/radiation effects , Cells, Cultured , Chromosome Aberrations/radiation effects , Dose-Response Relationship, Radiation , Embryonic Stem Cells/physiology , Mice , Micronucleus Tests , Radiation Dosage
16.
Antioxid Redox Signal ; 20(9): 1463-80, 2014 Mar 20.
Article in English | MEDLINE | ID: mdl-24180340

ABSTRACT

SIGNIFICANCE: There are accruing concerns on potential genotoxic agents present in the environment including low-dose ionizing radiation (LDIR) that naturally exists on earth's surface and atmosphere and is frequently used in medical diagnosis and nuclear industry. Although its long-term health risk is being evaluated and remains controversial, LDIR is shown to induce temporary but significant adaptive responses in mammalian cells and animals. The mechanisms guiding the mitochondrial function in LDIR-induced adaptive response represent a unique communication between DNA damage and cellular metabolism. Elucidation of the LDIR-regulated mitochondrial activity may reveal new mechanisms adjusting cellular function to cope with hazardous environmental stress. RECENT ADVANCES: Key cell cycle regulators, including Cyclin D1/CDK4 and Cyclin B1/cyclin-dependent kinase 1 (CDK1) complexes, are actively involved in the regulation of mitochondrial functions via phosphorylation of their mitochondrial targets. Accumulating new evidence supports a concept that the Cyclin B1/CDK1 complex acts as a mediator in the cross talk between radiation-induced DNA damage and mitochondrial functions to coordinate cellular responses to low-level genotoxic stresses. CRITICAL ISSUES: The LDIR-mediated mitochondrial activity via Cyclin B1/CDK1 regulation is an irreplaceable network that is able to harmonize vital cellular functions with adjusted mitochondrial metabolism to enhance cellular homeostasis. FUTURE DIRECTIONS: Further investigation of the coordinative mechanism that regulates mitochondrial activities in sublethal stress conditions, including LDIR, will reveal new insights of how cells cope with genotoxic injury and will be vital for future targeted therapeutic interventions that reduce environmental injury and cancer risk.


Subject(s)
Adaptation, Biological/radiation effects , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Mitochondria/physiology , Mitochondria/radiation effects , Radiation, Ionizing , Animals , Apoptosis/physiology , Apoptosis/radiation effects , Cell Cycle/physiology , Cell Cycle/radiation effects , Cyclin-Dependent Kinases/metabolism , Cyclins/metabolism , Humans , Mitochondrial Dynamics/physiology , Mitochondrial Dynamics/radiation effects , Molecular Chaperones/metabolism , Oxidation-Reduction , Oxidative Phosphorylation/radiation effects , Protein Transport , Radiation Dosage , Signal Transduction/radiation effects
17.
Orig Life Evol Biosph ; 43(6): 501-26, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24362711

ABSTRACT

Lichens, which are symbioses of a fungus and one or two photoautotrophs, frequently tolerate extreme environmental conditions. This makes them valuable model systems in astrobiological research to fathom the limits and limitations of eukaryotic symbioses. Various studies demonstrated the high resistance of selected extremotolerant lichens towards extreme, non-terrestrial abiotic factors including space exposure, hypervelocity impact simulations as well as space and Martian parameter simulations. This study focusses on the diverse set of secondary lichen compounds (SLCs) that act as photo- and UVR-protective substances. Five lichen species used in present-day astrobiological research were compared: Buellia frigida, Circinaria gyrosa, Rhizocarpon geographicum, Xanthoria elegans, and Pleopsidium chlorophanum. Detailed investigation of secondary substances including photosynthetic pigments was performed for whole lichen thalli but also for axenically cultivated mycobionts and photobionts by methods of UV/VIS-spectrophotometry and two types of high performance liquid chromatography (HPLC). Additionally, a set of chemical tests is presented to confirm the formation of melanic compounds in lichen and mycobiont samples. All investigated lichens reveal various sets of SLCs, except C. gyrosa where only melanin was putatively identified. Such studies will help to assess the contribution of SLCs on lichen extremotolerance, to understand the adaptation of lichens to prevalent abiotic stressors of the respective habitat, and to form a basis for interpreting recent and future astrobiological experiments. As most of the identified SLCs demonstrated a high capacity in absorbing UVR, they may also explain the high resistance of lichens towards non-terrestrial UVR.


Subject(s)
Adaptation, Biological/radiation effects , Lichens/metabolism , Ultraviolet Rays , Adaptation, Biological/physiology , Species Specificity
19.
J Proteome Res ; 12(11): 4799-806, 2013 Nov 01.
Article in English | MEDLINE | ID: mdl-24111740

ABSTRACT

Starting in 2007, we have grown soybean (Glycine max [L.] Merr. variety Soniachna) and flax (Linum usitatissimum, L. variety Kyivskyi) in the radio-contaminated Chernobyl area and analyzed the seed proteomes. In the second-generation flax seeds, we detected a 12% increase in oil content. To characterize the bases for this increase, seed development has been studied. Flax seeds were harvested in biological triplicate at 2, 4, and 6 weeks after flowering and at maturity from plants grown in nonradioactive and radio-contaminated plots in the Chernobyl area for two generations. Quantitative proteomic analyses based on 2-D gel electrophoresis (2-DE) allowed us to establish developmental profiles for 199 2-DE spots in both plots, out of which 79 were reliably identified by tandem mass spectrometry. The data suggest a statistically significant increased abundance of proteins associated with pyruvate biosynthesis via cytoplasmic glycolysis, L-malate decarboxylation, isocitrate dehydrogenation, and ethanol oxidation to acetaldehyde in early stages of seed development. This was followed by statistically significant increased abundance of ketoacyl-[acylcarrier protein] synthase I related to condensation of malonyl-ACP with elongating fatty acid chains. On the basis of these and previous data, we propose a preliminary model for plant adaptation to growth in a radio-contaminated environment. One aspect of the model suggests that changes in carbon assimilation and fatty acid biosynthesis are an integral part of plant adaptation.


Subject(s)
Adaptation, Biological/radiation effects , Chernobyl Nuclear Accident , Flax/genetics , Flax/radiation effects , Gene Expression Regulation, Plant/radiation effects , Models, Biological , Proteome/radiation effects , Adaptation, Biological/genetics , Carbon/metabolism , Cesium Radioisotopes/analysis , Electrophoresis, Gel, Two-Dimensional , Flax/chemistry , Gene Expression Regulation, Plant/genetics , Glycolysis , Linseed Oil/analysis , Proteome/genetics , Pyruvic Acid/metabolism , Seeds/chemistry , Seeds/growth & development , Seeds/radiation effects , Soil/chemistry , Strontium Radioisotopes/analysis , Tandem Mass Spectrometry , Ukraine
20.
PLoS Genet ; 8(3): e1002578, 2012.
Article in English | MEDLINE | ID: mdl-22457636

ABSTRACT

MicroRNA (miRNA)-mediated gene regulation is of critical functional importance in animals and is thought to be largely constrained during evolution. However, little is known regarding evolutionary changes of the miRNA network and their role in human evolution. Here we show that a number of miRNA binding sites display high levels of population differentiation in humans and thus are likely targets of local adaptation. In a subset we demonstrate that allelic differences modulate miRNA regulation in mammalian cells, including an interaction between miR-155 and TYRP1, an important melanosomal enzyme associated with human pigmentary differences. We identify alternate alleles of TYRP1 that induce or disrupt miR-155 regulation and demonstrate that these alleles are selected with different modes among human populations, causing a strong negative correlation between the frequency of miR-155 regulation of TYRP1 in human populations and their latitude of residence. We propose that local adaptation of microRNA regulation acts as a rheostat to optimize TYRP1 expression in response to differential UV radiation. Our findings illustrate the evolutionary plasticity of the microRNA regulatory network in recent human evolution.


Subject(s)
Binding Sites , Biological Evolution , Membrane Glycoproteins , MicroRNAs , Oxidoreductases , Selection, Genetic , Adaptation, Biological/radiation effects , Alleles , Gene Expression Regulation , Gene Regulatory Networks , Humans , Membrane Glycoproteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Oxidoreductases/metabolism , Polymorphism, Genetic , Selection, Genetic/radiation effects , Ultraviolet Rays
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