Drosophila melanogaster Show a Threshold Effect in Response to Radiation
ABSTRACT: We investigate the biological effects of radiation using Drosophila Melanogaster as a model organism, focusing on gene expression and lifespan analysis to determine the effect of different radiation doses. Our results support a threshold effect in response to radiation: no effect on lifespan and no permanent effect on gene expression is seen at doses below 10,000 Roentgens. Adult male Drosophila were irradiated 2 days after eclosion, with one of 6 radiation doses: 10; 1,000; 5,000; 10,000; 20,000 Roentgens. Samples were taken at 3 time points (2, 10 and 20 days post-irradiation).
Project description:We investigate the biological effects of radiation using Drosophila Melanogaster as a model organism, focusing on gene expression and lifespan analysis to determine the effect of different radiation doses. Our results support a threshold effect in response to radiation: no effect on lifespan and no permanent effect on gene expression is seen at doses below 10,000 Roentgens. Adult male Drosophila were irradiated 2 days after eclosion, with one of 6 radiation doses: 10; 1,000; 5,000; 10,000; 20,000 Roentgens. Samples were taken at 3 time points (2, 10 and 20 days post-irradiation).
Project description:We investigate the biological effects of radiation using adult Drosophila melanogaster as a model organism, focusing on gene expression and lifespan analysis to determine the effect of different radiation doses. Our results support a threshold effect in response to radiation: no effect on lifespan and no permanent effect on gene expression is seen at incident radiation levels below 100 J/kg. We also find that it is more appropriate to compare radiation effects in flies using the absorbed energy rather than incident radiation levels.
Project description:Biological indicators would be of use in radiation dosimetry in situations where an exposed person is not wearing a dosimeter, or when physical dosimeters are insufficient to estimate the risk caused by the radiation exposure. In this work, we investigate the use of gene expression as a dosimeter. Gene expression analysis was done on 15,222 genes of Drosophila melanogaster (fruit flies) at days 2, 10, and 20 postirradiation, with X-ray exposures of 10, 1000, 5000, 10,000, and 20,000 roentgens. Several genes were identified, which could serve as a biodosimeter in an irradiated D. melanogaster model. Many of these genes have human homologues. Six genes showed a linear response (R2 > 0.9) with dose at all time points. One of these genes, inverted repeat-binding protein, is a known DNA repair gene and has a human homologue (XRCC6). The lowest dose, 10 roentgen, is very low for fruit flies. If the lowest dose is excluded, 13 genes showed a linear response with dose at all time points. This includes 5 of 6 genes that were linear with all radiation doses included. Of these 13 genes, 4 have human homologues and 8 have known functions. The expression of this panel of genes, particularly those with human homologues, could potentially be used as the biological indicator of radiation exposure in dosimetry applications.
Project description:Studying of the effects of low doses of γ-irradiation is a crucial issue in different areas of interest, from environmental safety and industrial monitoring to aerospace and medicine. The goal of this work is to identify changes of lifespan and expression stress-sensitive genes in Drosophila melanogaster, exposed to low doses of γ-irradiation (5-40 cGy) on the imaginal stage of development. Although some changes in life extensity in males were identified (the effect of hormesis after the exposure to 5, 10 and 40 cGy) as well as in females (the effect of hormesis after the exposure to 5 and 40 cGy), they were not caused by the organism "physiological" changes. This means that the observed changes in life expectancy are not related to the changes of organism physiological functions after the exposure to low doses of ionizing radiation. The identified changes in gene expression are not dose-dependent, there is not any proportionality between dose and its impact on expression. These results reflect nonlinear effects of low dose radiation and sex-specific radio-resistance of the postmitotic cell state of Drosophila melanogaster imago.
Project description:<h4>Purpose</h4>Human chorionic gonadotrophin (hCG) has been used to induce ovulation and oocyte maturation. Although the most common dose of hCG used in IVF is 10,000 IU, there are reports that suggest 5,000 IU is sufficient to yield similar results. The objective of this study is to evaluate the dose dependent differences in gene expression of granulosa cells following various doses of hCG treatment.<h4>Methods</h4>Patients with polycystic ovarian syndrome (PCOS) were stimulated for IVF treatment. The hCG injection was either withheld or given at 5,000 or 10,000 IU. Granulosa cells from the follicular fluids have been collected for RNA isolation and analyzed using Affymetrix genechip arrays.<h4>Results</h4>Unsupervised hierarchical clustering based on whole gene expression revealed two distinct groups of patients in this experiment. All untreated patients were clustered together whereas hCG-treated patients separated to a different group regardless of the dose. A large number of the transcripts were similarly up- or down-regulated across both hCG doses (2229 and 1945 transcripts, respectively). However, we observed dose-dependent statistically significant differences in gene expression in only 15 transcripts.<h4>Conclusions</h4>Although hCG injection caused a major change in the gene expression profile of granulosa cells, 10,000 IU hCG resulted in minimal changes in the gene expression profiles of granulosa cells as compared with 5,000 IU. Thus, based on our results, we suggest the use of 10,000 IU hCG should be reconsidered in PCOS patients.
Project description:Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer's disease (AD). Although amyloid-β (Aβ) aggregation is a pathological hallmark of AD, the mechanisms by which Aβ peptides modulate cholinergic synaptic transmission and memory loss remain obscure. This study was aimed to investigate the potential synaptic modulation by Aβ of the cholinergic synapses between olfactory receptor neurons and projection neurons (PNs) in the olfactory lobe of the fruit fly.Cholinergic spontaneous and miniature excitatory postsynaptic current (mEPSC) were recorded with whole-cell patch clamp from PNs in Drosophila AD models expressing Aβ40, Aβ42, or Aβ42Arc peptides in neural tissue.In fly pupae (2 days before eclosion), overexpression of Aβ42 or Aβ42Arc, but not Aβ40, led to a significant decrease of mEPSC frequency, while overexpression of Aβ40, Aβ42, or Aβ42Arc had no significant effect on mEPSC amplitude. In contrast, Pavlovian olfactory associative learning and lifespan assays showed that both short-term memory and lifespan were decreased in the Drosophila models expressing Aβ40, Aβ42, or Aβ42Arc.Both electrophysiological and behavioral results showed an effect of Aβ peptide on cholinergic synaptic transmission and suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.
Project description:Wild-type Canton-S flies of Drosophila melanogaster were treated with ellagic acid at 100 ?M and 200 ?M concentrations. Longevity assay showed male flies fed with 200 ?M ellagic acid displayed longer mean lifespan and maximum lifespan than control flies. Female flies fed with 200 ?M ellagic acid laid less number of eggs than control. The eclosion time was less in female flies fed with 200 ?M ellagic acid. Ellagic acid fed female flies performed better than male flies and control flies for heat shock tolerance and starvation stress. Male flies treated with 100 ?M ellagic acid recovered faster from cold shock compared with control flies. Male and female flies treated with ellagic acid displayed increased survival following exposure to 5% hydrogen peroxide. Gene expression studies displayed upregulated expressions of CAT, dFOXO, ATG1, and SOD2 in ellagic acid-treated male flies, and upregulated expressions of dFOXO, CAT, and SOD2 in ellagic acid-treated female flies. Results from these studies show the pro-longevity effect of ellagic acid on Drosophila melanogaster.
Project description:Many mycophagous <i>Drosophila</i> species have adapted to tolerate high concentrations of mycotoxins, an ability not reported in any other eukaryotes. Although an association between mycophagy and mycotoxin tolerance has been established in many <i>Drosophila</i> species, the genetic mechanisms of the tolerance are unknown. This study presents the inter- and intraspecific variation in the mycotoxin tolerance trait. We studied the mycotoxin tolerance in four <i>Drosophila</i> species from four separate clades within the <i>immigrans</i>-<i>tripunctata</i> radiation from two distinct locations. The effect of mycotoxin treatment on 20 isofemale lines per species was studied using seven gross phenotypes: survival to pupation, survival to eclosion, development time to pupation and eclosion, thorax length, fecundity, and longevity. We observed interspecific variation among four species, with <i>D. falleni</i> being the most tolerant, followed by <i>D. recens</i>, <i>D. neotestacea</i>, and <i>D. tripunctata</i>, in that order. The results also revealed geographical variation and intraspecific genetic variation in mycotoxin tolerance. This report provides the foundation for further delineating the genetic mechanisms of the mycotoxin tolerance trait.
Project description:<h4>Background</h4>The molecular mechanisms that determine the organism's response to a variety of doses and modalities of stress factors are not well understood.<h4>Results</h4>We studied effects of ionizing radiation (144, 360 and 864 Gy), entomopathogenic fungus (10 and 100 CFU), starvation (16 h), and cold shock (+4, 0 and -4°C) on an organism's viability indicators (survival and locomotor activity) and transcriptome changes in the Drosophila melanogaster model. All stress factors but cold shock resulted in a decrease of lifespan proportional to the dose of treatment. However, stress-factors affected locomotor activity without correlation with lifespan. Our data revealed both significant similarities and differences in differential gene expression and the activity of biological processes under the influence of stress factors.<h4>Conclusions</h4>Studied doses of stress treatments deleteriously affect the organism's viability and lead to different changes of both general and specific cellular stress response mechanisms.
Project description:Long-lived cells such as terminally differentiated postmitotic neurons and glia must cope with the accumulation of damage over the course of an animal's lifespan. How long-lived cells deal with ageing-related damage is poorly understood. Here we show that polyploid cells accumulate in the adult fly brain and that polyploidy protects against DNA damage-induced cell death. Multiple types of neurons and glia that are diploid at eclosion, become polyploid in the adult Drosophila brain. The optic lobes exhibit the highest levels of polyploidy, associated with an elevated DNA damage response in this brain region. Inducing oxidative stress or exogenous DNA damage leads to an earlier onset of polyploidy, and polyploid cells in the adult brain are more resistant to DNA damage-induced cell death than diploid cells. Our results suggest polyploidy may serve a protective role for neurons and glia in adult Drosophila melanogaster brains.