Over 300 Radiation Caries Papers: Reflections From the Rearview Mirror
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SUBMITTER: Pedroso C
PROVIDER: S-EPMC9330023 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Investigation of health effects of low doses of radiation as a field of study has been riddled with difficulties since its inception. In this document we will use 100 mGy as the cutoff upper limit for low-dose radiation, borrowing this definition from the U.S. Department of Energy, although other agencies and researchers sometimes include up to five-fold higher doses under the same title. Difficulties in this area of research are most often ascribed to the fact that effects of low doses of radiation are subtle and difficult to distinguish from the plethora of other low-grade stresses. Thus, for example, most epidemiological studies include hundreds of thousands of samples and generate risk estimates that are statistically meaningful only when they are considered on a scale of hundreds or thousands of people. A logical approach to remedy the situation for low-dose research was to conduct well-controlled animal studies with hundreds of animals; nevertheless, even after many such studies were completed, our understanding of the biological basis for risk from low-dose radiation exposure is still not conclusive. In this paper we argue that the problem lies in the fact that our approach to animal studies is not comprehensive but conceptually binary. While some researchers apply epidemiological models to animal data, others look into molecular and cellular biology only. Very few studies are conducted to bridge this gap and consider how a realistic model of DNA damage could be integrated into a realistic model of radiation carcinogenesis.
| S-EPMC6226262 | biostudies-literature
Project description:The exponential increase in the number of scientific publications raises the question of whether the sciences are expanding into a fractured structure, making cross-field communication difficult. On the other hand, scientists may be motivated to learn extensively across fields to enhance their innovative capacity, and this may offset the negative effects of fragmentation. Through an investigation of the distances within and clustering of cross-sectional citation networks, this study presents evidence that fields of science become more integrated over time. The average citation distance between papers published in the same year decreased from ?5.33 to 3.18 steps between 1950 and 2018. This observation is attributed to the growth of cross-field communication throughout the entire period as well as the growing importance of high-impact papers to bridge networks in the same year. Three empirical findings support this conclusion. First, distances decreased between almost all disciplines throughout the time period. Second, inequality in the number of citations received by papers increased, and, as a consequence, the shortest paths in the network depend more on high-impact papers later in the period. Third, the dispersion of connections between fields increased continually. Moreover, these changes did not entail a lower level of clustering of citations. Both within- and cross-field citations show a similar rate of slowly growing clustering values in all years. The latter findings suggest that domain-spanning scholarly communication is partly enabled by new fields that connect disciplines.
| S-EPMC6825301 | biostudies-literature
Project description:The spatial distribution of radiation damage (assayed by increases in atomic B factors) to thaumatin and urease crystals at temperatures ranging from 25 to 300 K is reported. The nature of the damage changes dramatically at approximately 180 K. Above this temperature the role of solvent diffusion is apparent in thaumatin crystals, as solvent-exposed turns and loops are especially sensitive. In urease, a flap covering the active site is the most sensitive part of the molecule and nearby loops show enhanced sensitivity. Below 180 K sensitivity is correlated with poor local packing, especially in thaumatin. At all temperatures, the component of the damage that is spatially uniform within the unit cell accounts for more than half of the total increase in the atomic B factors and correlates with changes in mosaicity. This component may arise from lattice-level, rather than local, disorder. The effects of primary structure on radiation sensitivity are small compared with those of tertiary structure, local packing, solvent accessibility and crystal contacts.
| S-EPMC3489100 | biostudies-literature
Project description:BackgroundExpanded carrier screening (ECS) has become a common practice for identifying carriers of monogenic diseases. However, existing large gene panels are not well-tailored to Chinese populations. In this study, ECS testing for pathogenic variants of both single-nucleotide variants (SNVs) and copy number variants (CNVs) in 330 genes implicated in 342 autosomal recessive (AR) or X-linked diseases was carried out. We assessed the differences in allele frequencies specific to the Chinese population who have used assisted reproductive technology (ART) and the important genes to screen for in this population.MethodologyA total of 300 heterosexual couples were screened by our ECS panel using next-generation sequencing. A customed bioinformatic algorithm was used to analyze SNVs and CNVs. Guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology were adapted for variant interpretation. Pathogenic or likely pathogenic (P/LP) SNVs located in high homology regions/deletions and duplications of one or more exons in length were independently verified with other methods.Results64.83% of the patients were identified to be carriers of at least one of 342 hereditary conditions. We identified 622 P/LP variants, 4.18% of which were flagged as CNVs. The rate of at-risk couples was 3%. A total of 149 AR diseases accounted for 64.05% of the cumulative carrier rate, and 48 diseases had a carrier rate above 1/200 in the test.ConclusionAn expanded screening of inherited diseases by incorporating different variant types, especially CNVs, has the potential to reduce the occurrence of severe monogenic diseases in the offspring of patients using ART in China.
| S-EPMC10440320 | biostudies-literature
Project description:The desert locust Schistocerca gregaria is a well known migrating insect, travelling long distances in swarms containing millions of individuals. During November 2004, such a locust swarm reached the northern coast of the Gulf of Aqaba, coming from the Sinai desert towards the southeast. Upon reaching the coast, they avoided flying over the water, and instead flew north along the coast. Only after passing the tip of the gulf did they turn east again. Experiments with tethered locusts showed that they avoided flying over a light-reflecting mirror, and when given a choice of a non-polarizing reflecting surface and a surface that reflected linearly polarized light, they preferred to fly over the former. Our results suggest that locusts can detect the polarized reflections of bodies of water and avoid crossing them; at least when flying at low altitudes, they can therefore avoid flying over these dangerous areas.
| S-EPMC1626356 | biostudies-literature
Project description:Cognitive impairments are an important side effect after radiation exposure. Yet, it comes more and more into scientific focus that ionising radiation can resemble pathologies of neurodegenerative diseases such as Alzheimer´s. Here, we used a multidisciplinary approach to elucidate the effect of chronic low-dose irradiation exposure (1 mGy/day and 20 mGy/day) over 300 days (cumulative dose of 0.3 Gy and 6.0 Gy) on the murine ApoE-/- hippocampus as an Alzheimer´s model. By using mass spectrometry to quantify global expression levels of unmodified proteins, phospho-proteins and N-linked sialylated glycoproteins, we found nearly exclusive changes on the phospho-proteome at both doses. These proteins regulate signalling of synaptic plasticity and calcium-dependent signalling. We used synaptic plasticity-targeted transcriptomics, immunoblotting and ELISA to validate our findings and could identify that memory-related CREB signalling is reduced at both doses whereas Rac1-Cofilin signalling is only altered at 1 mGy/day. Interestingly, we noted a reduction in the number of activated microglia in the molecular layer of the hippocampus only at 1 mGy/day paralleled with reduced levels of TNFα mRNA and lipid peroxidation at this dose. Adult neurogenesis (Ki67, GFAP and NeuN as markers) and cell death (activated caspase-3) were not changed / initiated at both doses. Our analysis showed that several molecular targets induced by chronic low-dose radiation overlap with molecular targets of Alzheimer´s pathology. We suggest that chronic low-dose ionising radiation can be a potential confounder in Alzheimer´s disease.
2017-07-25 | PXD003969 | Pride
Project description:BackgroundThe mammalian gut harbors very complex and diverse microbiota that play an important role in intestinal homeostasis and host health. Exposure to radiation results in dysbiosis of the gut microbiota leading to detrimental pathophysiological changes to the host. To alleviate the effects of irradiation, several candidate countermeasures are under investigation. BIO 300, containing synthetic genistein formulated as an amorphous solid dispersion or as an aqueous suspension of nanoparticles, is a promising candidate under advanced development. The aim of this study was to investigate the effects of BIO 300 on the gut microbiome and metabolome of mice exposed to 60Co gamma-radiation. The gut microbiota and metabolome of control and drug-treated mice exposed to radiation was characterized by bacterial 16S rRNA amplicon sequencing and untargeted metabolomics.ResultsWe found that irradiation altered the Firmicutes/Bacteroidetes ratio and significantly decreased the relative abundance of Lactobacillus, both in BIO 300-treated and control mice; however, the ratio returned to near normal levels in BIO 300-treated mice by day 14 post-irradiation. Concomitantly, we also observed corrective shifts in metabolic pathways that were perturbed after irradiation.ConclusionsOverall, the data presented show that radiation exposure led to a relative depletion of commensals like Lactobacillus leading to an inflammatory metabolic phenotype while the majority of the drug-treated mice showed alleviation of this condition primarily by restoration of normal gut microbiota. These results indicate that the radioprotective effects of BIO 300, at least in part, may involve correction of the host-microbiome metabolic axis.
| S-EPMC8501697 | biostudies-literature
Project description:The unique hydrographic setting of the Bay of Bengal (BoB) makes it an ideal tropical marine system to study the influence of regional and global forcings on productivity and [CO2aq] through the late quaternary. Enormous fresh water flux into the BoB and consequent salinity stratification significantly weaken the convective mixing and wind driven processes which are commonly responsible for transport of nutrients to the euphotic zone driving primary productivity. Here we present a high resolution organic carbon-CaCO3 MAR and δ13CTOC records for the last 300 ky from the BoB. The results show significant productivity variation at marine isotope sub-stages and millennial timescales. Colder sub-stages and stadials (Dansgard-Oeschger cycle) show a boost in productivity which may be attributed to thinning of low salinity cap, thereby facilitating efficient nutrient transport across the euphotic zone by the combination of wind driven processes (entrainment and upwelling), convective mixing and cold core eddies. The [CO2aq] was a net result of global pCO2 variation and regional processes. Our long term high-resolution data indicates a possibility of marked change in productivity/biogeochemistry of BOB in the future due to global warming, thus affecting the coastal economy.
| S-EPMC5663938 | biostudies-literature
Project description:In an approach to generate Saccharomyces cerevisiae strains with increased intracellular copper amounts for technical applications we over-expressed the copper transporter CTR1 and a variant of CTR1 with a truncation in the C-terminus after the 300 amino acids (CTR1 delta-300). We determined the copper sensitivity of the generated strains and used inductively coupled plasma spectrometry (ICP-OES and ICP-MS) analysis to investigate the effects of over-expression of both constructs under excess copper on the cellular content of different elements in S. cerevisiae. In addition, we ran DNA microarray analysis to obtain the gene expression profile under the changed element contents. Over-expression of CTR1 increased the copper content in the cells up to 160% and 78 genes were differentially regulated. Over-expression of the truncated CTR1 delta-300 resulted in an increased copper, iron and zinc content of more than 200% and 980 genes showed differential expression. We found that transition metal ion homeostasis was disrupted in CTR1 delta-300 over-expressing strains under excess copper and that this was combined with a transcriptional remodelling of cellular processes
2014-01-28 | GSE44043 | GEO
Project description:Development of radiation medical countermeasures under the U.S. Food and Drug Administration Animal Rule requires the capability to translate an effective animal-to-human drug dose. One method of human dose translation is using a biomarker and determining drug doses that modulate the biomarker to the desired level. BIO 300 Oral Powder (BIO 300) is a prophylactic radiation medical countermeasure that is currently being developed following the Animal Rule. The present study aimed to identify biomarkers that can be used for human dose conversion by conducting transcriptomics of whole blood collected from BIO 300-treated CD2F1 mice in the presence and absence of total-body irradiation (TBI). Unirradiated mice were treated with vehicle or 50, 100, or 200 mg/kg BIO 300, and irradiated mice were treated with 200 mg/kg or BIO 300 or vehicle prior to TBI. Whole-blood samples were collected after the last dose of the drug and after irradiation. RNA sequencing demonstrated 100 and 200 mg/kg of BIO 300 doses caused significantly more differential gene expression at 48 h after drug dose compared to 50 mg/kg of BIO 300 (7648, 7680, and 55 significantly differently expressed genes, respectively). Interestingly, following TBI, there were no significantly differentially expressed genes between vehicle- and BIO 300-treated mice. Despite the lack of significant changes in gene expression, the transcriptomic profiles in both groups indicated differential changes in signaling pathways. Pathway analysis of the transcriptome profile from vehicle-treated/TBI mice revealed that many inflammatory signaling pathways were activated in these animals. Signaling pathways enriched in BIO 300-treated/TBI mice were involved in cellular stress and immune response and were predicted to be inhibited. In all, four signaling pathways of interest were identified that were differentially enriched in irradiated animals treated with BIO 300: pathogen-induced cytokine storm signaling, S100 family signaling, pulmonary fibrosis idiopathic signaling, and wound-healing signaling. These pathways should be explored to identify potential biomarkers of BIO 300 that can be used for human dose translation.
| S-EPMC11354227 | biostudies-literature