scholarly journals Genistein Induces Deleterious Effects during Its Acute Exposure in Swiss Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Prabhat Singh ◽  
Sharad Sharma ◽  
Srikanta Kumar Rath
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Global Gene Expression ◽  
Differentially Expressed ◽  
Therapeutic Effects ◽  
Biologically Relevant ◽  
Swiss Mice ◽  
Tissue Homogenates ◽  
Cellular Pathways

Genistein is a soy derived isoflavone. It has wide variety of therapeutic effects against certain diseases including cancer. Although toxic effects of genistein have been studied, its effect on the gene expression and the reason behind toxicity have not been identified yet. In the present study, genistein was administered to age and body weight matched Swiss mice at the doses of 125, 250, 500 and 1000 mg/kg. The biomarkers of hepatotoxicity in serum, liver histology, oxidative stress parameters in tissue homogenates, and global gene expression were examined. Elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels and degenerated liver tissue were observed in 500, and 1000 mg/kg genistein treated groups. Oxidative stress was significant at these doses as considerable increase in lipid peroxidation (LPO) and decrease in total glutathione (GSH) were observed. Gene expression analysis showed 40 differentially expressed genes at twofold change andP<0.05.Differentially expressed genes were corresponding to different biologically relevant pathways including metabolic and oxidative stress pathways. In 500 mg/kg group, Cyp4a14, Sult1e1, Gadd45g, Cidec, Mycs, and so forth genes were upregulated. These results suggested that the higher dose of genistein can produce several undesirable effects by affecting multiple cellular pathways.

scholarly journals Multitarget Effects of Danqi Pill on Global Gene Expression Changes in Myocardial Ischemia

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Qiyan Wang ◽  
Hui Meng ◽  
Qian Zhang ◽  
Tianjiao Shi ◽  
Xuefeng Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Ischemia ◽  
Differentially Expressed Genes ◽  
Sham Group ◽  
Gene Expression Pattern ◽  
Enrichment Analysis ◽  
Global Gene Expression ◽  
Differentially Expressed ◽  
Group Model ◽  
Model Group

Danqi pill (DQP) is a widely prescribed traditional Chinese medicine (TCM) in the treatment of cardiovascular diseases. The objective of this study is to systematically characterize altered gene expression pattern induced by myocardial ischemia (MI) in a rat model and to investigate the effects of DQP on global gene expression. Global mRNA expression was measured. Differentially expressed genes among the sham group, model group, and DQP group were analyzed. The gene ontology enrichment analysis and pathway analysis of differentially expressed genes were carried out. We quantified 10,813 genes. Compared with the sham group, expressions of 339 genes were upregulated and 177 genes were downregulated in the model group. The upregulated genes were enriched in extracellular matrix organization, response to wounding, and defense response pathways. Downregulated genes were enriched in fatty acid metabolism, pyruvate metabolism, PPAR signaling pathways, and so forth. This indicated that energy metabolic disorders occurred in rats with MI. In the DQP group, expressions of genes in the altered pathways were regulated back towards normal levels. DQP reversed expression of 313 of the 516 differentially expressed genes in the model group. This study provides insight into the multitarget mechanism of TCM in the treatment of complex diseases.

The Transcriptome of Immunomodulator-Resistant Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1772-1772
Author(s):  
Moritz Binder ◽  
S. Vincent Rajkumar ◽  
Martha Q. Lacy ◽  
Jessica L. Haug ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Differentially Expressed Genes ◽  
Research Funding ◽  
Differentially Expressed ◽  
Resistant Disease ◽  
Kaplan Meier ◽  
Gene Coding ◽  
Cellular Pathways

Introduction: While the molecular target of immunomodulators such as pomalidomide (POM) and lenalidomide (LEN) has been identified, the mechanisms underlying therapeutic resistance remain incompletely understood. The uniformly emerging resistance to therapy over time in the absence of identifiable cereblon pathway mutations in the majority of patients raises questions about alternative mechanisms including aberrant gene expression. Methods: We performed gene expression profiling using an Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray on CD138+ bone marrow cells from patients with relapsed / refractory (RRMM) and newly diagnosed (NDMM) multiple myeloma prior to initiating treatment. Patients were treated on two phase II clinical trial protocols (MC0789: POM ± dexamethasone in RRMM; MC0884: LEN ± dexamethasone in NDMM) between 2007 and 2012. We categorized patients based on their IMWG response as non-responders (SD) and responders (VGPR+). We selected 15 responders and 15 non-responders from MC0789 (n = 30) and compared overall survival, gene expression patterns, and involved cellular pathways between the two groups. We selected 5 responders and 5 non-responders from MC0884 (n = 10) for targeted validation of differentially expressed candidate genes. After data quality control and normalization of gene expression values, differential gene expression was estimated using limma. Statistical significance was adjusted for multiple testing in the discovery set using a false discovery rate-based approach for genome-wide experiments (q-value). We used Gene Ontology and PANTHER pathway analysis for functional annotation of differentially expressed genes. Overall survival estimates were calculated using the Kaplan-Meier method. Computation and visualization were performed in R. Results: Median age at treatment initiation on MC0789 was 65 years (40 - 82), 65% of the patients were male. Pomalidomide resistance was associated with an increase in mortality (median overall survival 1.6 versus 6.4 years, p = 0.009, Kaplan-Meier plot). There were 1076 differentially regulated genes between responders and non-responders (521 up- and 555 down-regulated, q < 0.050 for all genes, volcano plot). Expression of CRBN was 1.5-fold down-regulated in non-responders (q = 0.005). Supervised hierarchical clustering of the top 500 differentially expressed genes demonstrated distinct patterns in pomalidomide-resistant disease (heatmap). Gene ontology analysis revealed protein synthesis as one of the most enriched biological processes (bar graph). Pathway analysis showed a 6-fold enrichment (FDR = 0.007) of the ubiquitin proteasome pathway in pomalidomide-resistant disease. Differentially expressed genes involved key protein degradation pathways, epigenetic modifiers, and transcription factors. Targeted validation in MC0884 revealed 13 common genes with at least 1.5-fold differential expression (5 up- and 8 down-regulated), 12 of which have previously been implicated in the regulation of apoptosis, tumor glucose metabolism, Rho and Wnt signaling, miRNA-driven resistance to chemotherapy, and ubiquitin-dependent protein degradation (Table and Sankey diagram). The most up-regulated gene in non-responders was MYRIP, a gene coding for a vesicle trafficking protein associated with platinum resistance and suppression of pro-apoptotic BCL-2 family members in solid malignancies. The most down-regulated gene was FRZB, a gene coding for a negative regulator of Wnt signaling, previously implicated in the progression of monoclonal gammopathy of undetermined significance to multiple myeloma. Conclusions: Overall survival of patients with pomalidomide-resistant RRMM remains poor. Pomalidomide resistance was associated with differential gene expression in several potentially targetable cellular pathways beyond the known drug target cereblon. Targeted validation of candidate genes revealed common cellular pathways in immunomodulator-resistant disease. Elucidating the exact molecular mechanisms underlying immunomodulator resistance is of considerable interest for biomarker development and the identification of novel therapeutic targets and warrants further exploration. Figure Disclosures Lacy: Celgene: Research Funding. Dispenzieri:Celgene: Research Funding; Alnylam: Research Funding; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Akcea: Consultancy; Takeda: Research Funding. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

Costimulatory Blockade (CSB) during Mixed Lymphocyte Reaction (MLR) Prevents IL27 Upregulation and Signalling.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4878-4878
Author(s):  
Gullu Gorgun ◽  
Patrick Philpot ◽  
Kamila Naxerova ◽  
Isaac Kohane ◽  
Lee Nadler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
T Cells ◽  
Cell Differentiation ◽  
Differentially Expressed Genes ◽  
Ex Vivo ◽  
Global Gene Expression ◽  
Th1 Cell ◽  
Cellular Pathways

Abstract Numerous methods for selectively depleting or manipulating alloantigen (alloAg) specific CD4 T cells (CD4 T) are being studied for their potential in improving transplant outcomes by limiting GVHD or graft rejection. Although some methods target specific molecules (e.g. costimulatory receptors and ligands, activation antigens), the effects of these methods on “off-target” CD4 T cellular pathways and functions as well as effects on other PBMC, direct or indirect, have not been well characterized. Such effects may impact significantly on clinical efficacy and/or may shed light on the mechanism of action of manipulated PBMC in a complex in vivo milieu. To understand the molecular impact on bystander PBMC of inducing alloAg specific CD4 T anergy by CSB via disruption of the positive costimulatory signal between B7.1 and B7.2 on antigen presenting cells (APC) and CD28 on CD4 T by humanized anti B7.1/B7.2 monoclonal antibodies (MoAbs), we have used global gene expression profiling (GEP). Mimicking our ex vivo clinical anergization protocol, we used PBMC obtained from fully-HLA mismatched healthy volunteers (n=12 pairs) to perform an ex vivo primary MLR +/− anti B7.1/B7.2 MoAbs. CD28:B7 CSB inhibited mean proliferation by 73% after 72 hours of MLR. GEP was performed using Affymetrix hu133 plus2 chips on monocytes (Mo), CD4 and CD8 T cells, and B and NK cells purified from the MLR. Differentially expressed genes between cells from MLR +/− CSB were determined by SAM and EBAM analysis. Despite the low published frequency (1–10%) of alloAg specific CD4 T, we could detect global gene expression variance between CD4 T isolated from MLR +/− CSB (P≤0.05) suggesting effects on non-alloAg specific CD4 T. Use of the Ingenuity pathway analyzer to classify these differentially expressed genes by specific cellular pathways showed most were involved in cell proliferation and differentiation. Differences in IL27 downstream signaling molecules (DSM) in Mo and CD4 T were pronounced. IL27 is a member of IL12 cytokine family produced by APC and is a heterodimer of p28 and EBV-Induced gene 3 (EBI3). The IL27 receptor (IL27R) WSX1 is expressed on CD4 T. IL27 regulates adaptive immunity by controlling T cell proliferation, Th1 cell differentiation and IFNγ synthesis. Both p28 and EBI3 transcriptional and translational levels were decreased in Mo from MLR + CSB. Expression of STAT3, an IL27 pathway DSM was also decreased. After CD28:B7 CSB, CD4 T exhibited decreased expression of the IL27R and also inactivation of IL27 DSM including pSTAT1 and NFκB at both the transcriptional and translational levels. Consistent with a negative effect on Th1 differentiation, intracytoplasmic cytokine (ICC) analysis showed decreased expression of type 1 cytokines IL2 and IFNγ in CD4 T from MLR + CSB. ICC also showed decreased expression of the type 1 cytokine IL15 and increased expression of the type 2 cytokine IL10 in Mo from MLR + CSB. These results suggest that CD28:B7 signaling during MLR is required for Mo production of IL27. Decreased expression of IL27 and its DSMs pSTAT1 and NFκB1 after CSB with antiB7 MoAbs may contribute to CD4 T alloAg anergy induction by suppressing effector cytokines and Th1 cell differentiation. The observation that CD28:B7 modulates IL27 and IL27R emphasizes that targeted therapies used in the complex environment of human PBMC may have effects not predicted by in vitro clonal systems. Such effects may be important in the functional outcome of the intervention.

scholarly journals Comparative Transcriptional Analysis of Human Macrophages Exposed to Animal and Human Isolates of Mycobacterium avium Subspecies paratuberculosis with Diverse Genotypes

2006 ◽  
Vol 74 (11) ◽  
pp. 6046-6056 ◽  
Author(s):  
Alifiya S. Motiwala ◽  
Harish K. Janagama ◽  
Michael L. Paustian ◽  
Xiaochun Zhu ◽  
John P. Bannantine ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Protein Kinase ◽  
Differentially Expressed Genes ◽  
Mycobacterium Avium ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Cell Receptor ◽  
Differentially Expressed ◽  
Anti Inflammatory

ABSTRACT Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease in animals and has been hypothesized to be associated with Crohn's disease in humans. Recently, M. avium subsp. paratuberculosis isolates recovered from Crohn's disease patients were shown to have limited diversity, implying the existence of human disease-associated genotypes and strain sharing with animals (A. H. Ghadiali et al., J. Clin. Microbiol. 42:5345-5348, 2004). To explore whether these genotypic differences or similarities among human and animal isolates translated to functionally significant attributes such as variance in host preference and/or difference in magnitude of infections, we performed a global scale analysis of M. avium subsp. paratuberculosis isolates that were representative of different genotypes and host species using DNA microarrays. Genome-wide characterization of the transcriptional changes was carried out using a human monocytic cell line (THP-1 cells) in response to different genotypes of M. avium subsp. paratuberculosis isolates recovered from various hosts. We identified several differentially expressed genes during early intracellular infection, including those involved in common canonical pathways such as NF-κB, interleukin-6 (IL-6), mitogen-activated protein kinase/extracellular signal-regulated kinase, and Jun N-terminal protein kinase signaling, as well as genes involved in T helper type 1 (Th1) responses (such as CCL5 ligand) and those that encode several proinflammatory cytokines and chemokine receptors. The cattle and human isolates of M. avium subsp. paratuberculosis, regardless of their short sequence repeat (SSR) genotype, induced similar global gene expression patterns in THP-1 cells. They differentially regulated genes necessary for cell survival without causing major alterations in proinflammatory genes. In contrast, the sheep isolates representing diverse SSR genotypes closely resembled the global gene expression pattern of an M. avium subsp. avium isolate, and they significantly up-regulated proinflammatory genes related to IL-6, T-cell receptor, B-cell receptor, and death receptor signaling within THP-1 cells. Additionally, we demonstrated consistency among infecting genotypes of M. avium subsp. paratuberculosis isolated from diverse hosts [cattle (n = 2), human (n = 3), sheep (n = 2), and bison (n = 1)] in quantitative reverse transcription-PCR analysis of seven differentially expressed genes. While the levels of expression induced by the bison isolate were different compared with cattle or human isolates, they followed the common anti-inflammatory, antiapoptotic trend. Our data suggest that the macrophage responses to M. avium subsp. paratuberculosis isolates from cattle and human sources, regardless of genotype, follow a common theme of anti-inflammatory responses, an attribute likely associated with successful infection and persistence. However, these expression patterns differ significantly from those in THP-1 cells infected with sheep isolates of M. avium subsp. paratuberculosis or the M. avium subsp. avium isolate. These data provide a transcriptional basis for a variety of pathophysiological changes observed during early stages of infection by different strains of M. avium subsp. paratuberculosis, a first step in understanding trait-allele association in this economically important disease.

scholarly journals Modulation of Gene Expression in Liver of Hibernating Asiatic Toads (Bufo gargarizans)

2018 ◽  
Vol 19 (8) ◽  
pp. 2363 ◽  
Author(s):  
Long Jin ◽  
Jian Ping Yu ◽  
Zai Jun Yang ◽  
Juha Merilä ◽  
Wen Bo Liao
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Regulation Of Gene Expression ◽  
Global Gene Expression ◽  
Contractile Proteins ◽  
Energy Utilization ◽  
Differentially Expressed ◽  
Conservation Strategy ◽  
Bufo Gargarizans ◽  
And Shifts

Hibernation is an effective energy conservation strategy that has been widely adopted by animals to cope with unpredictable environmental conditions. The liver, in particular, plays an important role in adaptive metabolic adjustment during hibernation. Mammalian studies have revealed that many genes involved in metabolism are differentially expressed during the hibernation period. However, the differentiation in global gene expression between active and torpid states in amphibians remains largely unknown. We analyzed gene expression in the liver of active and torpid Asiatic toads (Bufo gargarizans) using RNA-sequencing. In addition, we evaluated the differential expression of genes between females and males. A total of 1399 genes were identified as differentially expressed between active and torpid females. Of these, the expressions of 395 genes were significantly elevated in torpid females and involved genes responding to stresses, as well as contractile proteins. The expression of 1004 genes were significantly down-regulated in torpid females, most which were involved in metabolic depression and shifts in the energy utilization. Of the 715 differentially expressed genes between active and torpid males, 337 were up-regulated and 378 down-regulated. A total of 695 genes were differentially expressed between active females and males, of which 655 genes were significantly down-regulated in males. Similarly, 374 differentially expressed genes were identified between torpid females and males, with the expression of 252 genes (mostly contractile proteins) being significantly down-regulated in males. Our findings suggest that expression of many genes in the liver of B. gargarizans are down-regulated during hibernation. Furthermore, there are marked sex differences in the levels of gene expression, with females showing elevated levels of gene expression as compared to males, as well as more marked down-regulation of gene-expression in torpid males than females.

scholarly journals Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Rowan AlEjielat ◽  
Anas Khaleel ◽  
Amneh H. Tarkhan
Keyword(s):  
Gene Expression ◽  
Ankylosing Spondylitis ◽  
Differentially Expressed Genes ◽  
Gene Network ◽  
Disease Diagnosis ◽  
Receptor Activation ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Inflammatory Disorder ◽  
Data Set

Abstract Background Ankylosing spondylitis (AS) is a rare inflammatory disorder affecting the spinal joints. Although we know some of the genetic factors that are associated with the disease, the molecular basis of this illness has not yet been fully elucidated, and the genes involved in AS pathogenesis have not been entirely identified. The current study aimed at constructing a gene network that may serve as an AS gene signature and biomarker, both of which will help in disease diagnosis and the identification of therapeutic targets. Previously published gene expression profiles of 16 AS patients and 16 gender- and age-matched controls that were profiled on the Illumina HumanHT-12 V3.0 Expression BeadChip platform were mined. Patients were Portuguese, 21 to 64 years old, were diagnosed based on the modified New York criteria, and had Bath Ankylosing Spondylitis Disease Activity Index scores > 4 and Bath Ankylosing Spondylitis Functional Index scores > 4. All patients were receiving only NSAIDs and/or sulphasalazine. Functional enrichment and pathway analysis were performed to create an interaction network of differentially expressed genes. Results ITM2A, ICOS, VSIG10L, CD59, TRAC, and CTLA-4 were among the significantly differentially expressed genes in AS, but the most significantly downregulated genes were the HLA-DRB6, HLA-DRB5, HLA-DRB4, HLA-DRB3, HLA-DRB1, HLA-DQB1, ITM2A, and CTLA-4 genes. The genes in this study were mostly associated with the regulation of the immune system processes, parts of cell membrane, and signaling related to T cell receptor and antigen receptor, in addition to some overlaps related to the IL2 STAT signaling, as well as the androgen response. The most significantly over-represented pathways in the data set were associated with the “RUNX1 and FOXP3 which control the development of regulatory T lymphocytes (Tregs)” and the “GABA receptor activation” pathways. Conclusions Comprehensive gene analysis of differentially expressed genes in AS reveals a significant gene network that is involved in a multitude of important immune and inflammatory pathways. These pathways and networks might serve as biomarkers for AS and can potentially help in diagnosing the disease and identifying future targets for treatment.

scholarly journals Behavioral sensitization induced by methamphetamine causes differential alterations in gene expression and histone acetylation of the prefrontal cortex in rats

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hui Li ◽  
Jing-An Chen ◽  
Qian-Zhi Ding ◽  
Guan-Yi Lu ◽  
Ning Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Histone Acetylation ◽  
Differentially Expressed Genes ◽  
Behavioral Sensitization ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Adult Rats ◽  
Mrna Microarray ◽  
H3 Acetylation

Abstract Background Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats. Methods We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays. Results In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 genes were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure. Conclusions The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.

scholarly journals Impact of aging on gene expression response to x-ray irradiation using mouse blood

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Constantinos G. Broustas ◽  
Axel J. Duval ◽  
Sally A. Amundson
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
X Rays ◽  
Gene Expression Response ◽  
X Ray ◽  
The Impact ◽  
Old Mice ◽  
Radiation Biodosimetry ◽  
Young Mice

AbstractAs a radiation biodosimetry tool, gene expression profiling is being developed using mouse and human peripheral blood models. The impact of dose, dose-rate, and radiation quality has been studied with the goal of predicting radiological tissue injury. In this study, we determined the impact of aging on the gene expression profile of blood from mice exposed to radiation. Young (2 mo) and old (21 mo) male mice were irradiated with 4 Gy x-rays, total RNA was isolated from whole blood 24 h later, and subjected to whole genome microarray analysis. Pathway analysis of differentially expressed genes revealed young mice responded to x-ray exposure by significantly upregulating pathways involved in apoptosis and phagocytosis, a process that eliminates apoptotic cells and preserves tissue homeostasis. In contrast, the functional annotation of senescence was overrepresented among differentially expressed genes from irradiated old mice without enrichment of phagocytosis pathways. Pathways associated with hematologic malignancies were enriched in irradiated old mice compared with irradiated young mice. The fibroblast growth factor signaling pathway was underrepresented in older mice under basal conditions. Similarly, brain-related functions were underrepresented in unirradiated old mice. Thus, age-dependent gene expression differences should be considered when developing gene signatures for use in radiation biodosimetry.

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