Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

International Nuclear Information System (INIS)

Luo, Hanwen; Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng; Ping, Jie; Xu, Dan; Ma, Lu; Chen, Liaobin; Wang, Hui

2014-01-01

Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine-induced

Drought-induced trans-generational tradeoff between stress tolerance and defence: consequences for range limits?

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Alsdurf, Jacob D; Ripley, Tayler J; Matzner, Steven L; Siemens, David H

2013-01-01

Areas just across species range boundaries are often stressful, but even with ample genetic variation within and among range-margin populations, adaptation towards stress tolerance across range boundaries often does not occur. Adaptive trans-generational plasticity should allow organisms to circumvent these problems for temporary range expansion; however, range boundaries often persist. To investigate this dilemma, we drought stressed a parent generation of Boechera stricta (A.Gray) A. Löve & D. Löve, a perennial wild relative of Arabidopsis, representing genetic variation within and among several low-elevation range margin populations. Boechera stricta is restricted to higher, moister elevations in temperate regions where generalist herbivores are often less common. Previous reports indicate a negative genetic correlation (genetic tradeoff) between chemical defence allocation and abiotic stress tolerance that may prevent the simultaneous evolution of defence and drought tolerance that would be needed for range expansion. In growth chamber experiments, the genetic tradeoff became undetectable among offspring sib-families whose parents had been drought treated, suggesting that the stress-induced trans-generational plasticity may circumvent the genetic tradeoff and thus enable range expansion. However, the trans-generational effects also included a conflict between plastic responses (environmental tradeoff); offspring whose parents were drought treated were more drought tolerant, but had lower levels of glucosinolate toxins that function in defence against generalist herbivores. We suggest that either the genetic or environmental tradeoff between defence allocation and stress tolerance has the potential to contribute to range limit development in upland mustards.

Epigenetic dysregulation underlies radiation-induced transgenerational genome instability in vivo

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Koturbash, Igor; Baker, Mike; Loree, Jonathan; Kutanzi, Kristy; Hudson, Darryl; Pogribny, Igor; Sedelnikova, Olga; Bonner, William; Kovalchuk, Olga

2006-01-01

Purpose: Although modern cancer radiation therapy has led to increased patient survival rates, the risk of radiation treatment-related complications is becoming a growing problem. Among various complications, radiation also poses a threat to the progeny of exposed parents. It causes transgenerational genome instability that is linked to transgenerational carcinogenesis. Although the occurrence of transgenerational genome instability, which manifests as elevated delayed and nontargeted mutation, has been well documented, the mechanisms by which it arises remain obscure. We hypothesized that epigenetic alterations may play a pivotal role in the molecular etiology of transgenerational genome instability. Methods and Materials: We studied the levels of cytosine DNA methylation in somatic tissues of unexposed offspring upon maternal, paternal, or combined parental exposure. Results: We observed a significant loss of global cytosine DNA methylation in the thymus tissue of the offspring upon combined parental exposure. The loss of DNA methylation was paralleled by a significant decrease in the levels of maintenance (DNMT1) and de novo methyltransferases DNMT3a and 3b and methyl-CpG-binding protein MeCP2. Along with profound changes in DNA methylation, we noted a significant accumulation of DNA strand breaks in thymus, which is a radiation carcinogenesis target organ. Conclusions: The observed changes were indicative of a profound epigenetic dysregulation in the offspring, which in turn could lead to genome destabilization and possibly could serve as precursor for transgenerational carcinogenesis. Future studies are clearly needed to address the cellular and carcinogenic repercussions of those changes

The Role of DNA Methylation Changes in Radiation-Induced Transgenerational Genomic Instability and Bystander Effects in cranial irradiated Mice

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Zhang, Meng; Sun, Yeqing; Gao, Yinglong; Zhang, Baodong

Heavy-ion radiation could lead to genome instability in the germline, and therefore to transgenerational genome and epigenome instability in offspring of exposed males. The exact mechanisms of radiation-induced genome instability in directly exposed and in bystander organ remain obscure, yet accumulating evidence points to the role of DNA methylation changes in genome instability development. The potential of localized body-part exposures to affect the germline and thus induce genome and epigenome changes in the progeny has not been studied. To investigate whether or not the paternal cranial irradiation can exert deleterious changes in the protected germline and the offsprings, we studied the alteration of DNA methylation in the shielded testes tissue. Here we report that the localized paternal cranial irradiation results in a significant altered DNA methylation in sperm cells and leads to a profound epigenetic dysregulation in the unexposed progeny conceived 3 months after paternal exposure. The possible molecular mechanisms and biological consequences of the observed changes are discussed. Keywords: Heavy-ion radiation; Transgenerational effect; Genomic Instability Bystander Effects; DNA methylation.

Epigenetic Transgenerational Actions of Vinclozolin on the Development of Disease and Cancer

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Skinner, Michael K.; Anway, Matthew D.

2018-01-01

Exposure to an environmental endocrine disruptor (e.g., vinclozolin) during embryonic gonadal sex determination appears to alter the male germ line epigenome and subsequently promotes transgenerational adult onset disease. The epigenetic mechanism involves the induction of new imprinted-like genes/DNA sequences in the germ line that appear to transmit disease phenotypes. The disease phenotypes include testis abnormalities, prostate disease, kidney disease, immune abnormalities, and tumor development. This epigenetic transgenerational disease mechanism provides a unique perspective from which to view inheritable adult onset disease states, such as cancer, and ultimately offers new insights into novel diagnostic and therapeutic strategies. PMID:17956218

Elusive inheritance: Transgenerational effects and epigenetic inheritance in human environmental disease.

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Martos, Suzanne N; Tang, Wan-Yee; Wang, Zhibin

2015-07-01

Epigenetic mechanisms involving DNA methylation, histone modification, histone variants and nucleosome positioning, and noncoding RNAs regulate cell-, tissue-, and developmental stage-specific gene expression by influencing chromatin structure and modulating interactions between proteins and DNA. Epigenetic marks are mitotically inherited in somatic cells and may be altered in response to internal and external stimuli. The idea that environment-induced epigenetic changes in mammals could be inherited through the germline, independent of genetic mechanisms, has stimulated much debate. Many experimental models have been designed to interrogate the possibility of transgenerational epigenetic inheritance and provide insight into how environmental exposures influence phenotypes over multiple generations in the absence of any apparent genetic mutation. Unexpected molecular evidence has forced us to reevaluate not only our understanding of the plasticity and heritability of epigenetic factors, but of the stability of the genome as well. Recent reviews have described the difference between transgenerational and intergenerational effects; the two major epigenetic reprogramming events in the mammalian lifecycle; these two events making transgenerational epigenetic inheritance of environment-induced perturbations rare, if at all possible, in mammals; and mechanisms of transgenerational epigenetic inheritance in non-mammalian eukaryotic organisms. This paper briefly introduces these topics and mainly focuses on (1) transgenerational phenotypes and epigenetic effects in mammals, (2) environment-induced intergenerational epigenetic effects, and (3) the inherent difficulties in establishing a role for epigenetic inheritance in human environmental disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mercury-induced epigenetic transgenerational inheritance of abnormal neurobehavior is correlated with sperm epimutations in zebrafish.

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Michael J Carvan

Full Text Available Methylmercury (MeHg is a ubiquitous environmental neurotoxicant, with human exposures predominantly resulting from fish consumption. Developmental exposure of zebrafish to MeHg is known to alter their neurobehavior. The current study investigated the direct exposure and transgenerational effects of MeHg, at tissue doses similar to those detected in exposed human populations, on sperm epimutations (i.e., differential DNA methylation regions [DMRs] and neurobehavior (i.e., visual startle and spontaneous locomotion in zebrafish, an established human health model. F0 generation embryos were exposed to MeHg (0, 1, 3, 10, 30, and 100 nM for 24 hours ex vivo. F0 generation control and MeHg-exposed lineages were reared to adults and bred to yield the F1 generation, which was subsequently bred to the F2 generation. Direct exposure (F0 generation and transgenerational actions (F2 generation were then evaluated. Hyperactivity and visual deficit were observed in the unexposed descendants (F2 generation of the MeHg-exposed lineage compared to control. An increase in F2 generation sperm epimutations was observed relative to the F0 generation. Investigation of the DMRs in the F2 generation MeHg-exposed lineage sperm revealed associated genes in the neuroactive ligand-receptor interaction and actin-cytoskeleton pathways being effected, which correlate to the observed neurobehavioral phenotypes. Developmental MeHg-induced epigenetic transgenerational inheritance of abnormal neurobehavior is correlated with sperm epimutations in F2 generation adult zebrafish. Therefore, mercury can promote the epigenetic transgenerational inheritance of disease in zebrafish, which significantly impacts its environmental health considerations in all species including humans.

Transgenerational inheritance of modified DNA methylation patterns and enhanced tolerance induced by heavy metal stress in rice (Oryza sativa L.).

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Ou, Xiufang; Zhang, Yunhong; Xu, Chunming; Lin, Xiuyun; Zang, Qi; Zhuang, Tingting; Jiang, Lili; von Wettstein, Diter; Liu, Bao

2012-01-01

DNA methylation is sensitive and responsive to stressful environmental conditions. Nonetheless, the extent to which condition-induced somatic methylation modifications can impose transgenerational effects remains to be fully understood. Even less is known about the biological relevance of the induced epigenetic changes for potentially altered well-being of the organismal progenies regarding adaptation to the specific condition their progenitors experienced. We analyzed DNA methylation pattern by gel-blotting at genomic loci representing transposable elements and protein-coding genes in leaf-tissue of heavy metal-treated rice (Oryza sativa) plants (S0), and its three successive organismal generations. We assessed expression of putative genes involved in establishing and/or maintaining DNA methylation patterns by reverse transcription (RT)-PCR. We measured growth of the stressed plants and their unstressed progenies vs. the control plants. We found (1) relative to control, DNA methylation patterns were modified in leaf-tissue of the immediately treated plants, and the modifications were exclusively confined to CHG hypomethylation; (2) the CHG-demethylated states were heritable via both maternal and paternal germline, albeit often accompanying further hypomethylation; (3) altered expression of genes encoding for DNA methyltransferases, DNA glycosylase and SWI/SNF chromatin remodeling factor (DDM1) were induced by the stress; (4) progenies of the stressed plants exhibited enhanced tolerance to the same stress their progenitor experienced, and this transgenerational inheritance of the effect of condition accompanying heritability of modified methylation patterns. Our findings suggest that stressful environmental condition can produce transgenerational epigenetic modifications. Progenies of stressed plants may develop enhanced adaptability to the condition, and this acquired trait is inheritable and accord with transmission of the epigenetic modifications. We suggest

Evolution of transgenerational immunity in invertebrates.

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Pigeault, R; Garnier, R; Rivero, A; Gandon, S

2016-09-28

Over a decade ago, the discovery of transgenerational immunity in invertebrates shifted existing paradigms on the lack of sophistication of their immune system. Nonetheless, the prevalence of this trait and the ecological factors driving its evolution in invertebrates remain poorly understood. Here, we develop a theoretical host-parasite model and predict that long lifespan and low dispersal should promote the evolution of transgenerational immunity. We also predict that in species that produce both philopatric and dispersing individuals, it may pay to have a plastic allocation strategy with a higher transgenerational immunity investment in philopatric offspring because they are more likely to encounter locally adapted pathogens. We review all experimental studies published to date, comprising 21 invertebrate species in nine different orders, and we show that, as expected, longevity and dispersal correlate with the transfer of immunity to offspring. The validity of our prediction regarding the plasticity of investment in transgenerational immunity remains to be tested in invertebrates, but also in vertebrate species. We discuss the implications of our work for the study of the evolution of immunity, and we suggest further avenues of research to expand our knowledge of the impact of transgenerational immune protection in host-parasite interactions. © 2016 The Author(s).

Genome-Wide Locations of Potential Epimutations Associated with Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Using a Sequential Machine Learning Prediction Approach.

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Haque, M Muksitul; Holder, Lawrence B; Skinner, Michael K

2015-01-01

Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation involves germline transmitted epimutations. The primary epimutations identified involve altered differential DNA methylation regions (DMRs). Different environmental toxicants have been shown to promote exposure (i.e., toxicant) specific signatures of germline epimutations. Analysis of genomic features associated with these epimutations identified low-density CpG regions (machine learning computational approach to predict all potential epimutations in the genome. A number of previously identified sperm epimutations were used as training sets. A novel machine learning approach using a sequential combination of Active Learning and Imbalance Class Learner analysis was developed. The transgenerational sperm epimutation analysis identified approximately 50K individual sites with a 1 kb mean size and 3,233 regions that had a minimum of three adjacent sites with a mean size of 3.5 kb. A select number of the most relevant genomic features were identified with the low density CpG deserts being a critical genomic feature of the features selected. A similar independent analysis with transgenerational somatic cell epimutation training sets identified a smaller number of 1,503 regions of genome-wide predicted sites and differences in genomic feature contributions. The predicted genome-wide germline (sperm) epimutations were found to be distinct from the predicted somatic cell epimutations. Validation of the genome-wide germline predicted sites used two recently identified transgenerational sperm epimutation signature sets from the pesticides dichlorodiphenyltrichloroethane (DDT) and methoxychlor (MXC) exposure lineage F3 generation. Analysis of this positive validation data set showed a 100% prediction accuracy for all the DDT-MXC sperm epimutations. Observations further elucidate the genomic features associated with transgenerational germline epimutations and identify a genome

Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis.

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Anway, Matthew D; Rekow, Stephen S; Skinner, Michael K

2008-10-01

Exposure of gestating female rats to the anti-androgenic endocrine disruptor vinclozolin has been shown to induce transgenerational adult onset disease phenotypes. The current study, was designed to compare the actions of vinclozolin to the known anti-androgenic compound flutamide. The gestating female rats were exposed to intraperitoneal injections during embryonic day 8-14 (E8-E14) to 100mg/kg/day vinclozolin or flutamide at either 5mg or 20mg/kg/day. As previously observed, vinclozolin induced a transgenerational testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm number. In contrast, the flutamide exposures resulted in a testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm numbers in the F1 generation only, and not the F2 and F3 generation adult males. Interestingly, some of the low dose (5mg/kg) flutamide F2 generation offspring developed spinal agenesis and supernummery development (polymelia) of limbs. Although the actions of vinclozolin and flutamide appear similar in the F1 generation males, the transgenerational effects of vinclozolin do not appear to be acting through the same anti-androgenic mechanism as flutamide.

Evolution of transgenerational immunity in invertebrates

OpenAIRE

Pigeault, R.; Garnier, R.; Rivero, A.; Gandon, S.

2016-01-01

Over a decade ago, the discovery of transgenerational immunity in invertebrates shifted existing paradigms on the lack of sophistication of their immune system. Nonetheless, the prevalence of this trait and the ecological factors driving its evolution in invertebrates remain poorly understood. Here, we develop a theoretical host–parasite model and predict that long lifespan and low dispersal should promote the evolution of transgenerational immunity. We also predict that in species that produ...

Dioxin (TCDD induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

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Mohan Manikkam

Full Text Available Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

Genome-Wide Locations of Potential Epimutations Associated with Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Using a Sequential Machine Learning Prediction Approach.

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M Muksitul Haque

Full Text Available Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation involves germline transmitted epimutations. The primary epimutations identified involve altered differential DNA methylation regions (DMRs. Different environmental toxicants have been shown to promote exposure (i.e., toxicant specific signatures of germline epimutations. Analysis of genomic features associated with these epimutations identified low-density CpG regions (<3 CpG / 100bp termed CpG deserts and a number of unique DNA sequence motifs. The rat genome was annotated for these and additional relevant features. The objective of the current study was to use a machine learning computational approach to predict all potential epimutations in the genome. A number of previously identified sperm epimutations were used as training sets. A novel machine learning approach using a sequential combination of Active Learning and Imbalance Class Learner analysis was developed. The transgenerational sperm epimutation analysis identified approximately 50K individual sites with a 1 kb mean size and 3,233 regions that had a minimum of three adjacent sites with a mean size of 3.5 kb. A select number of the most relevant genomic features were identified with the low density CpG deserts being a critical genomic feature of the features selected. A similar independent analysis with transgenerational somatic cell epimutation training sets identified a smaller number of 1,503 regions of genome-wide predicted sites and differences in genomic feature contributions. The predicted genome-wide germline (sperm epimutations were found to be distinct from the predicted somatic cell epimutations. Validation of the genome-wide germline predicted sites used two recently identified transgenerational sperm epimutation signature sets from the pesticides dichlorodiphenyltrichloroethane (DDT and methoxychlor (MXC exposure lineage F3 generation. Analysis of this positive validation

Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior.

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Michael K Skinner

Full Text Available Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3 removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease.

Ancestral TCDD exposure promotes epigenetic transgenerational inheritance of imprinted gene Igf2: Methylation status and DNMTs

International Nuclear Information System (INIS)

Ma, Jing; Chen, Xi; Liu, Yanan; Xie, Qunhui; Sun, Yawen; Chen, Jingshan; Leng, Ling; Yan, Huan; Zhao, Bin; Tang, Naijun

2015-01-01

Ancestral TCDD exposure could induce epigenetic transgenerational phenotypes, which may be mediated in part by imprinted gene inheritance. The aim of our study was to evaluate the transgenerational effects of ancestral TCDD exposure on the imprinted gene insulin-like growth factor-2 (Igf2) in rat somatic tissue. TCDD was administered daily by oral gavage to groups of F0 pregnant SD rats at dose levels of 0 (control), 200 or 800 ng/kg bw during gestation day 8–14. Animal transgenerational model of ancestral exposure to TCDD was carefully built, avoiding sibling inbreeding. Hepatic Igf2 expression of the TCDD male progeny was decreased concomitantly with hepatic damage and increased activities of serum hepatic enzymes both in the F1 and F3 generation. Imprinted Control Region (ICR) of Igf2 manifested a hypermethylated pattern, whereas methylation status in the Differentially Methylated Region 2 (DMR2) showed a hypomethylated manner in the F1 generation. These epigenetic alterations in these two regions maintained similar trends in the F3 generation. Meanwhile, the expressions of DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) changed in a non-monotonic manner both in the F1 and F3 generation. This study provides evidence that ancestral TCDD exposure may promote epigenetic transgenerational alterations of imprinted gene Igf2 in adult somatic tissue. - Highlights: • Ancestral TCDD exposure induces epigenetic transgenerational inheritance. • Ancestral TCDD exposure affects methylation status in ICR and DMR2 region of Igf2. • DNMTs play a role in TCDD induced epigenetic transgenerational changes of Igf2.

Ancestral TCDD exposure promotes epigenetic transgenerational inheritance of imprinted gene Igf2: Methylation status and DNMTs

Energy Technology Data Exchange (ETDEWEB)

Ma, Jing; Chen, Xi; Liu, Yanan [Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070 (China); Xie, Qunhui [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Sun, Yawen; Chen, Jingshan; Leng, Ling; Yan, Huan [Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070 (China); Zhao, Bin, E-mail: binzhao@rcees.ac.cn [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Tang, Naijun, E-mail: tangnaijun@tijmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070 (China)

2015-12-01

Ancestral TCDD exposure could induce epigenetic transgenerational phenotypes, which may be mediated in part by imprinted gene inheritance. The aim of our study was to evaluate the transgenerational effects of ancestral TCDD exposure on the imprinted gene insulin-like growth factor-2 (Igf2) in rat somatic tissue. TCDD was administered daily by oral gavage to groups of F0 pregnant SD rats at dose levels of 0 (control), 200 or 800 ng/kg bw during gestation day 8–14. Animal transgenerational model of ancestral exposure to TCDD was carefully built, avoiding sibling inbreeding. Hepatic Igf2 expression of the TCDD male progeny was decreased concomitantly with hepatic damage and increased activities of serum hepatic enzymes both in the F1 and F3 generation. Imprinted Control Region (ICR) of Igf2 manifested a hypermethylated pattern, whereas methylation status in the Differentially Methylated Region 2 (DMR2) showed a hypomethylated manner in the F1 generation. These epigenetic alterations in these two regions maintained similar trends in the F3 generation. Meanwhile, the expressions of DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) changed in a non-monotonic manner both in the F1 and F3 generation. This study provides evidence that ancestral TCDD exposure may promote epigenetic transgenerational alterations of imprinted gene Igf2 in adult somatic tissue. - Highlights: • Ancestral TCDD exposure induces epigenetic transgenerational inheritance. • Ancestral TCDD exposure affects methylation status in ICR and DMR2 region of Igf2. • DNMTs play a role in TCDD induced epigenetic transgenerational changes of Igf2.

Offspring reaction norms shaped by parental environment: interaction between within- and trans-generational plasticity of inducible defenses

OpenAIRE

Luquet, Emilien; Tariel, Juliette

2016-01-01

Background Within-generational plasticity (WGP) and transgenerational plasticity (TGP) are mechanisms allowing rapid adaptive responses to fluctuating environments without genetic change. These forms of plasticity have often been viewed as independent processes. Recent evidence suggests that WGP is altered by the environmental conditions experienced by previous generations (i.e., TGP). In the context of inducible defenses, one of the most studied cases of plasticity, the WGP x TGP interaction...

Contrasting patterns of transgenerational plasticity in ecologically distinct congeners.

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Sultan, Sonia E; Barton, Kasey; Wilczek, Amity M

2009-07-01

Stressful parental environments can influence offspring size and development either adaptively or maladaptively, yet little is known about species' differences in this complex aspect of phenotypic plasticity. We performed a reciprocal split-brood experiment to compare transgenerational plasticity in response to drought stress in two closely related annual plant species. We raised inbred replicate parent plants of eight genotypes per species in dry vs. moist soil to generate offspring of each genetic line that differed only in parental environment, then monitored seedling development in both dry and moist conditions. Individuals of the two species expressed contrasting patterns of transgenerational plasticity for traits important to seedling drought tolerance. In Polygonum persicaria, a weedy generalist found in moist, dry, and variably dry sites, drought-stressed plants produced offspring with longer and more rapidly extending root systems and greater biomass when growing in dry soil. In contrast, in P. hydropiper, a non-weedy congener restricted to moist habitats, the offspring of drought-stressed parents had reduced root system development and seedling biomass in dry soil. In P. persicaria, transgenerational and immediate adaptive plasticity combined to produce drought-adapted seedling phenotypes. These results make clear that characteristic patterns of transgenerational plasticity can contribute to ecological diversity among species.

Role of epigenetics in developmental biology and transgenerational inheritance.

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Skinner, Michael K

2011-03-01

The molecular mechanisms involved in developmental biology and cellular differentiation have traditionally been considered to be primarily genetic. Environmental factors that influence early life critical windows of development generally do not have the capacity to modify genome sequence, nor promote permanent genetic modifications. Epigenetics provides a molecular mechanism for environment to influence development, program cellular differentiation, and alter the genetic regulation of development. The current review discusses how epigenetics can cooperate with genetics to regulate development and allow for greater plasticity in response to environmental influences. This impacts area such as cellular differentiation, tissue development, environmental induced disease etiology, epigenetic transgenerational inheritance, and the general systems biology of organisms and evolution. Copyright © 2011 Wiley-Liss, Inc.

Tertiary Epimutations – A Novel Aspect of Epigenetic Transgenerational Inheritance Promoting Genome Instability

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McCarrey, John R.; Lehle, Jake D.; Raju, Seetha S.; Wang, Yufeng; Nilsson, Eric E.; Skinner, Michael K.

2016-01-01

Exposure to environmental factors can induce the epigenetic transgenerational inheritance of disease. Alterations to the epigenome termed “epimutations” include “primary epimutations” which are epigenetic alterations in the absence of genetic change and “secondary epimutations” which form following an initial genetic change. To determine if secondary epimutations contribute to transgenerational transmission of disease following in utero exposure to the endocrine disruptor vinclozolin, we exposed pregnant female rats carrying the lacI mutation-reporter transgene to vinclozolin and assessed the frequency of mutations in kidney tissue and sperm recovered from F1 and F3 generation progeny. Our results confirm that vinclozolin induces primary epimutations rather than secondary epimutations, but also suggest that some primary epimutations can predispose a subsequent accelerated accumulation of genetic mutations in F3 generation descendants that have the potential to contribute to transgenerational phenotypes. We therefore propose the existence of “tertiary epimutations” which are initial primary epimutations that promote genome instability leading to an accelerated accumulation of genetic mutations. PMID:27992467

Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.

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Abhay Sharma

Full Text Available Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1 adults after treating F(0 adult males with PTZ and of F(2 adults resulting from a cross between F(1 males and normal females. Surprisingly, microarray clustering showed F(1 male profile as closest to F(1 female and F(0 male profile closest to F(2 male. Differentially expressed genes in F(1 males, F(1 females and F(2 males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2 males. Next, we generated microarray expression profiles of adult testis from F(0 and F(1 males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying

Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.

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Sharma, Abhay; Singh, Priyanka

2009-06-02

Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ) induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1) adults after treating F(0) adult males with PTZ and of F(2) adults resulting from a cross between F(1) males and normal females. Surprisingly, microarray clustering showed F(1) male profile as closest to F(1) female and F(0) male profile closest to F(2) male. Differentially expressed genes in F(1) males, F(1) females and F(2) males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2) males. Next, we generated microarray expression profiles of adult testis from F(0) and F(1) males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying the

Developmental programming and transgenerational transmission of obesity.

Science.gov (United States)

Vickers, M H

2014-01-01

The global obesity pandemic is often causally linked to marked changes in diet and lifestyle, namely marked increases in dietary intakes of high-energy diets and concomitant reductions in physical activity levels. However, far less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from environmental perturbations during the early-life period. Human and animal studies have highlighted the link between alterations in the early-life environment and increased susceptibility to obesity and related metabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and maternal obesity, has been shown to lead to transgenerational transmission of metabolic disorders. This association has been conceptualised as the developmental programming hypothesis whereby the impact of environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the physiology of the offspring. Further, evidence to date suggests that this developmental programming is a transgenerational phenomenon, with a number of studies showing transmission of programming effects to subsequent generations, even in the absence of continued environmental stressors, thus perpetuating a cycle of obesity and metabolic disorders. The mechanisms responsible for these transgenerational effects remain poorly understood; evidence to date suggests a number of potential mechanisms underpinning the transgenerational transmission of the developmentally programmed phenotype through both the maternal and paternal lineage. Transgenerational phenotype transmission is often seen as a form of epigenetic inheritance with evidence showing both germline and somatic inheritance of epigenetic modifications leading to phenotype changes across generations. However, there is also evidence for non-genomic components as well as an interaction between the developing fetus with the in utero

Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease

OpenAIRE

Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K

2008-01-01

Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1–F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti...

Molecular processes of transgenerational acclimation to a warming ocean

KAUST Repository

Veilleux, Heather D.; Ryu, Tae Woo; Donelson, Jennifer M.; van Herwerden, Lynne; Seridi, Loqmane; Ghosheh, Yanal; Berumen, Michael L.; Leggat, William; Ravasi, Timothy; Munday, Philip L.

2015-01-01

Some animals have the remarkable capacity to acclimate across generations to projected future climate change1, 2, 3, 4; however, the underlying molecular processes are unknown. We sequenced and assembled de novo transcriptomes of adult tropical reef fish exposed developmentally or transgenerationally to projected future ocean temperatures and correlated the resulting expression profiles with acclimated metabolic traits from the same fish. We identified 69 contigs representing 53 key genes involved in thermal acclimation of aerobic capacity. Metabolic genes were among the most upregulated transgenerationally, suggesting shifts in energy production for maintaining performance at elevated temperatures. Furthermore, immune- and stress-responsive genes were upregulated transgenerationally, indicating a new complement of genes allowing the second generation of fish to better cope with elevated temperatures. Other differentially expressed genes were involved with tissue development and transcriptional regulation. Overall, we found a similar suite of differentially expressed genes among developmental and transgenerational treatments. Heat-shock protein genes were surprisingly unresponsive, indicating that short-term heat-stress responses may not be a good indicator of long-term acclimation capacity. Our results are the first to reveal the molecular processes that may enable marine fishes to adjust to a future warmer environment over multiple generations.

Molecular processes of transgenerational acclimation to a warming ocean

KAUST Repository

Veilleux, Heather D.

2015-07-20

Some animals have the remarkable capacity to acclimate across generations to projected future climate change1, 2, 3, 4; however, the underlying molecular processes are unknown. We sequenced and assembled de novo transcriptomes of adult tropical reef fish exposed developmentally or transgenerationally to projected future ocean temperatures and correlated the resulting expression profiles with acclimated metabolic traits from the same fish. We identified 69 contigs representing 53 key genes involved in thermal acclimation of aerobic capacity. Metabolic genes were among the most upregulated transgenerationally, suggesting shifts in energy production for maintaining performance at elevated temperatures. Furthermore, immune- and stress-responsive genes were upregulated transgenerationally, indicating a new complement of genes allowing the second generation of fish to better cope with elevated temperatures. Other differentially expressed genes were involved with tissue development and transcriptional regulation. Overall, we found a similar suite of differentially expressed genes among developmental and transgenerational treatments. Heat-shock protein genes were surprisingly unresponsive, indicating that short-term heat-stress responses may not be a good indicator of long-term acclimation capacity. Our results are the first to reveal the molecular processes that may enable marine fishes to adjust to a future warmer environment over multiple generations.

The importance of trans-generational effects in Lepidoptera.

Science.gov (United States)

Woestmann, Luisa; Saastamoinen, Marjo

2016-10-01

The importance of trans-generational effects in shaping an individuals' phenotype and fitness, and consequently even impacting population dynamics is increasingly apparent. Most of the research on trans-generational effects still focuses on plants, mammals, and birds. In the past few years, however, increasing number of studies, especially on maternal effects, have highlighted their importance also in many insect systems. Lepidoptera, specifically butterflies, have been used as model systems for studying the role of phenotypic plasticity within generations. As ectotherms, they are highly sensitive to environmental variation, and indeed many butterflies show adaptive phenotypic plasticity in response to environmental conditions. Here, we synthesize what is known about trans-generational effects in Lepidoptera, compile evidence for different environmental cues that are important drivers of trans-generational effects, and point out which offspring traits are mainly impacted. Finally, we emphasize directions for future research that are needed for better understanding of the adaptive nature of trans-generational effects in Lepidoptera in particular, but potentially also in other organisms.

Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome.

Directory of Open Access Journals (Sweden)

Carlos Guerrero-Bosagna

2010-09-01

Full Text Available Previous observations have demonstrated that embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes transgenerational adult onset disease such as male infertility, kidney disease, prostate disease, immune abnormalities and tumor development. The current study investigates genome-wide promoter DNA methylation alterations in the sperm of F3 generation rats whose F0 generation mother was exposed to vinclozolin. A methylated DNA immunoprecipitation with methyl-cytosine antibody followed by a promoter tilling microarray (MeDIP-Chip procedure was used to identify 52 different regions with statistically significant altered methylation in the sperm promoter epigenome. Mass spectrometry bisulfite analysis was used to map the CpG DNA methylation and 16 differential DNA methylation regions were confirmed, while the remainder could not be analyzed due to bisulfite technical limitations. Analysis of these validated regions identified a consensus DNA sequence (motif that associated with 75% of the promoters. Interestingly, only 16.8% of a random set of 125 promoters contained this motif. One candidate promoter (Fam111a was found to be due to a copy number variation (CNV and not a methylation change, suggesting initial alterations in the germline epigenome may promote genetic abnormalities such as induced CNV in later generations. This study identifies differential DNA methylation sites in promoter regions three generations after the initial exposure and identifies common genome features present in these regions. In addition to primary epimutations, a potential indirect genetic abnormality was identified, and both are postulated to be involved in the epigenetic transgenerational inheritance observed. This study confirms that an environmental agent has the ability to induce epigenetic transgenerational changes in the sperm epigenome.

Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome.

Science.gov (United States)

Guerrero-Bosagna, Carlos; Settles, Matthew; Lucker, Ben; Skinner, Michael K

2010-09-30

Previous observations have demonstrated that embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes transgenerational adult onset disease such as male infertility, kidney disease, prostate disease, immune abnormalities and tumor development. The current study investigates genome-wide promoter DNA methylation alterations in the sperm of F3 generation rats whose F0 generation mother was exposed to vinclozolin. A methylated DNA immunoprecipitation with methyl-cytosine antibody followed by a promoter tilling microarray (MeDIP-Chip) procedure was used to identify 52 different regions with statistically significant altered methylation in the sperm promoter epigenome. Mass spectrometry bisulfite analysis was used to map the CpG DNA methylation and 16 differential DNA methylation regions were confirmed, while the remainder could not be analyzed due to bisulfite technical limitations. Analysis of these validated regions identified a consensus DNA sequence (motif) that associated with 75% of the promoters. Interestingly, only 16.8% of a random set of 125 promoters contained this motif. One candidate promoter (Fam111a) was found to be due to a copy number variation (CNV) and not a methylation change, suggesting initial alterations in the germline epigenome may promote genetic abnormalities such as induced CNV in later generations. This study identifies differential DNA methylation sites in promoter regions three generations after the initial exposure and identifies common genome features present in these regions. In addition to primary epimutations, a potential indirect genetic abnormality was identified, and both are postulated to be involved in the epigenetic transgenerational inheritance observed. This study confirms that an environmental agent has the ability to induce epigenetic transgenerational changes in the sperm epigenome.

Grandpaternal-induced transgenerational dietary reprogramming of the unfolded protein response in skeletal muscle

DEFF Research Database (Denmark)

Alm, Petter S; de Castro Barbosa, Thais; Barrès, Romain

2017-01-01

OBJECTIVE: Parental nutrition and lifestyle impact the metabolic phenotype of the offspring. We have reported that grandpaternal chronic high-fat diet (HFD) transgenerationally impairs glucose metabolism in subsequent generations. Here we determined whether grandpaternal diet transgenerationally....... Gene set enrichment analysis (GSEA) was performed to determine pathways reprogrammed by grandpaternal diet. RESULTS: GSEA revealed an enrichment of the unfolded protein response pathway in skeletal muscle of grand-offspring from HFD-fed grandfathers compared to grand-offspring of chow-fed males....... Activation of the stress sensor (ATF6α), may be a pivotal point whereby this pathway is activated. Interestingly, skeletal muscle from F1-offspring was not affected in a similar manner. No major changes were observed in the skeletal muscle lipidome profile due to grandpaternal diet. CONCLUSIONS...

Transgenerational effects of stress exposure on offspring phenotypes in apomictic dandelion.

Directory of Open Access Journals (Sweden)

Koen J F Verhoeven

Full Text Available Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various stresses was previously shown to heritably alter DNA methylation patterns. In this study we explore whether these induced changes are accompanied by heritable effects on offspring phenotypes. We observed effects of parental jasmonic acid treatment on offspring specific leaf area and on offspring interaction with a generalist herbivore; and of parental nutrient stress on offspring root-shoot biomass ratio, tissue P-content and leaf morphology. Some of the effects appeared to enhance offspring ability to cope with the same stresses that their parents experienced. Effects differed between apomictic genotypes and were not always consistently observed between different experiments, especially in the case of parental nutrient stress. While this context-dependency of the effects remains to be further clarified, the total set of results provides evidence for the existence of transgenerational effects in apomictic dandelions. Zebularine treatment affected the within-generation response to nutrient stress, pointing at a role of DNA methylation in phenotypic plasticity to nutrient environments. This study shows that stress exposure in apomictic dandelions can cause transgenerational phenotypic effects, in addition to previously demonstrated transgenerational DNA methylation effects.

Transgenerational effects of stress exposure on offspring phenotypes in apomictic dandelion.

Science.gov (United States)

Verhoeven, Koen J F; van Gurp, Thomas P

2012-01-01

Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various stresses was previously shown to heritably alter DNA methylation patterns. In this study we explore whether these induced changes are accompanied by heritable effects on offspring phenotypes. We observed effects of parental jasmonic acid treatment on offspring specific leaf area and on offspring interaction with a generalist herbivore; and of parental nutrient stress on offspring root-shoot biomass ratio, tissue P-content and leaf morphology. Some of the effects appeared to enhance offspring ability to cope with the same stresses that their parents experienced. Effects differed between apomictic genotypes and were not always consistently observed between different experiments, especially in the case of parental nutrient stress. While this context-dependency of the effects remains to be further clarified, the total set of results provides evidence for the existence of transgenerational effects in apomictic dandelions. Zebularine treatment affected the within-generation response to nutrient stress, pointing at a role of DNA methylation in phenotypic plasticity to nutrient environments. This study shows that stress exposure in apomictic dandelions can cause transgenerational phenotypic effects, in addition to previously demonstrated transgenerational DNA methylation effects.

Genome-Wide Locations of Potential Epimutations Associated with Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Using a Sequential Machine Learning Prediction Approach

OpenAIRE

Haque, M. Muksitul; Holder, Lawrence B.; Skinner, Michael K.

2015-01-01

Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation involves germline transmitted epimutations. The primary epimutations identified involve altered differential DNA methylation regions (DMRs). Different environmental toxicants have been shown to promote exposure (i.e., toxicant) specific signatures of germline epimutations. Analysis of genomic features associated with these epimutations identified low-density CpG regions (

Local adaptation in transgenerational responses to predators

Science.gov (United States)

Walsh, Matthew R.; Castoe, Todd; Holmes, Julian; Packer, Michelle; Biles, Kelsey; Walsh, Melissa; Munch, Stephan B.; Post, David M.

2016-01-01

Environmental signals can induce phenotypic changes that span multiple generations. Along with phenotypic responses that occur during development (i.e. ‘within-generation’ plasticity), such ‘transgenerational plasticity’ (TGP) has been documented in a diverse array of taxa spanning many environmental perturbations. New theory predicts that temporal stability is a key driver of the evolution of TGP. We tested this prediction using natural populations of zooplankton from lakes in Connecticut that span a large gradient in the temporal dynamics of predator-induced mortality. We reared more than 120 clones of Daphnia ambigua from nine lakes for multiple generations in the presence/absence of predator cues. We found that temporal variation in mortality selects for within-generation plasticity while consistently strong (or weak) mortality selects for increased TGP. Such results provide us the first evidence for local adaptation in TGP and argue that divergent ecological conditions select for phenotypic responses within and across generations. PMID:26817775

Local adaptation in transgenerational responses to predators.

Science.gov (United States)

Walsh, Matthew R; Castoe, Todd; Holmes, Julian; Packer, Michelle; Biles, Kelsey; Walsh, Melissa; Munch, Stephan B; Post, David M

2016-01-27

Environmental signals can induce phenotypic changes that span multiple generations. Along with phenotypic responses that occur during development (i.e. 'within-generation' plasticity), such 'transgenerational plasticity' (TGP) has been documented in a diverse array of taxa spanning many environmental perturbations. New theory predicts that temporal stability is a key driver of the evolution of TGP. We tested this prediction using natural populations of zooplankton from lakes in Connecticut that span a large gradient in the temporal dynamics of predator-induced mortality. We reared more than 120 clones of Daphnia ambigua from nine lakes for multiple generations in the presence/absence of predator cues. We found that temporal variation in mortality selects for within-generation plasticity while consistently strong (or weak) mortality selects for increased TGP. Such results provide us the first evidence for local adaptation in TGP and argue that divergent ecological conditions select for phenotypic responses within and across generations. © 2016 The Author(s).

Transgenerational stress-adaption: an opportunity for ecological epigenetics.

Science.gov (United States)

Weinhold, Arne

2018-01-01

In the recent years, there has been considerable interest to investigate the adaptive transgenerational plasticity of plants and how a "stress memory" can be transmitted to the following generation. Although, increasing evidence suggests that transgenerational adaptive responses have widespread ecological relevance, the underlying epigenetic processes have rarely been elucidated. On the other hand, model plant species have been deeply investigated in their genome-wide methylation landscape without connecting this to the ecological reality of the plant. What we need is the combination of an ecological understanding which plant species would benefit from transgenerational epigenetic stress-adaption in their natural habitat, combined with a deeper molecular analysis of non-model organisms. Only such interdisciplinary linkage in an ecological epigenetic study could unravel the full potential that epigenetics could play for the transgenerational stress-adaption of plants.

MET-2-Dependent H3K9 Methylation Suppresses Transgenerational Small RNA Inheritance.

Science.gov (United States)

Lev, Itamar; Seroussi, Uri; Gingold, Hila; Bril, Roberta; Anava, Sarit; Rechavi, Oded

2017-04-24

In C. elegans, alterations to chromatin produce transgenerational effects, such as inherited increase in lifespan and gradual loss of fertility. Inheritance of histone modifications can be induced by double-stranded RNA-derived heritable small RNAs. Here, we show that the mortal germline phenotype, which is typical of met-2 mutants, defective in H3K9 methylation, depends on HRDE-1, an argonaute that carries small RNAs across generations, and is accompanied by accumulated transgenerational misexpression of heritable small RNAs. We discovered that MET-2 inhibits small RNA inheritance, and, as a consequence, induction of RNAi in met-2 mutants leads to permanent RNAi responses that do not terminate even after more than 30 generations. We found that potentiation of heritable RNAi in met-2 animals results from global hyperactivation of the small RNA inheritance machinery. Thus, changes in histone modifications can give rise to drastic transgenerational epigenetic effects, by controlling the overall potency of small RNA inheritance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transgenerational plasticity mitigates the impact of global warming to offspring sex ratios.

Science.gov (United States)

Donelson, Jennifer M; Munday, Philip L

2015-08-01

Global warming poses a threat to organisms with temperature-dependent sex determination because it can affect operational sex ratios. Using a multigenerational experiment with a marine fish, we provide the first evidence that parents developing from early life at elevated temperatures can adjust their offspring gender through nongenetic and nonbehavioural means. However, this adjustment was not possible when parents reproduced, but did not develop, at elevated temperatures. Complete restoration of the offspring sex ratio occurred when parents developed at 1.5 °C above the present-day average temperature for one generation. However, only partial improvement in the sex ratio occurred at 3.0 °C above average conditions, even after two generations, suggesting a limitation to transgenerational plasticity when developmental temperature is substantially increased. This study highlights the potential for transgenerational plasticity to ameliorate some impacts of climate change and that development from early life may be essential for expression of transgenerational plasticity in some traits. © 2015 John Wiley & Sons Ltd.

Transgenerational acclimation of fishes to climate change and ocean acidification.

Science.gov (United States)

Munday, Philip L

2014-01-01

There is growing concern about the impacts of climate change and ocean acidification on marine organisms and ecosystems, yet the potential for acclimation and adaptation to these threats is poorly understood. Whereas many short-term experiments report negative biological effects of ocean warming and acidification, new studies show that some marine species have the capacity to acclimate to warmer and more acidic environments across generations. Consequently, transgenerational plasticity may be a powerful mechanism by which populations of some species will be able to adjust to projected climate change. Here, I review recent advances in understanding transgenerational acclimation in fishes. Research over the past 2 to 3 years shows that transgenerational acclimation can partially or fully ameliorate negative effects of warming, acidification, and hypoxia in a range of different species. The molecular and cellular pathways underpinning transgenerational acclimation are currently unknown, but modern genetic methods provide the tools to explore these mechanisms. Despite the potential benefits of transgenerational acclimation, there could be limitations to the phenotypic traits that respond transgenerationally, and trade-offs between life stages, that need to be investigated. Future studies should also test the potential interactions between transgenerational plasticity and genetic evolution to determine how these two processes will shape adaptive responses to environmental change over coming decades.

Environmentally induced epigenetic transgenerational inheritance of disease susceptibility.

Science.gov (United States)

Nilsson, Eric E; Skinner, Michael K

2015-01-01

Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure-specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed with regard to disease etiology. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal effects of the scid mutation on radiation-induced transgenerational instability in mice.

NARCIS (Netherlands)

Hatch, T.; Derijck, A.H.A.; Black, P.D.; Heijden, G.W. van der; Boer, P. de; Dubrova, Y.E.

2007-01-01

The results of a number of recent studies show that mutation rates in the offspring of irradiated parents are substantially elevated, however, the effect of parental genotype on transgenerational instability remains poorly understood. Here, we have analysed the mutation frequency at an expanded

Trans-generational effects induced by alpha and gamma ionizing radiations at Daphnia magna

International Nuclear Information System (INIS)

Parisot, Florian

2015-01-01

Anthropogenic activities related to the nuclear industry contribute to continuous discharges of radionuclides into terrestrial and aquatic ecosystems. Over the past decades, the ecological risk of ionizing radiation has become a growing public, regulatory and scientific concern for ecosystems protection. Until recently, only few studies focus on exposure situations at low doses of irradiation, although these situations are representative of realistic environmental conditions. Understanding how ionizing radiation affects species over several generations and at various levels of biological organization is a major research goal in radioecology. The aim of this PhD was to bring new knowledge on the effects of ionizing radiation during a multi-generational expose of the aquatic invertebrate, Daphnia magna. A two-step strategy was implemented. First, an external gamma radiation at environmentally relevant dose rates was performed on D. magna over three successive generations (F0, F1 and F2). The objective of this experiment was to examine whether low dose rates of radiation induced increasing effects on survival, growth and reproduction of daphnids over generations and to test a possible accumulation and transmission of DNA alterations from adults to offspring. Results showed an accumulation and a transmission of DNA alterations over generations, together with an increase in effect severity on growth and reproduction from generation F0 to generation F2. Transiently more efficient DNA repair leading to some recovery at the organism level was suggested in generation F1. Second, data from the external gamma irradiation and those from an earlier study of internal alpha contamination were analyzed with DEBtox models (Dynamic Energy Budget applied to toxicology), to identify and compare the causes of the trans-generational increase in effect severity between the two types of radiation. In each case, two distinct metabolic modes of action were necessary to explain effects on

The transgenerational transmission of refugee trauma

DEFF Research Database (Denmark)

Dalgård, Nina Thorup; Montgomery, Edith

2017-01-01

Purpose The purpose of this paper is to explore the role of family functioning in the transgenerational transmission of trauma in a sample of 30 refugee families with traumatized parents and children without a history of direct trauma exposure from the Middle East. Design/methodology/approach Based...... and lower scores on the SDQ. Originality/value These findings suggest that the transgenerational transmission of trauma may be associated with family functioning and have implications for interventions at several levels....

Vinclozolin--the lack of a transgenerational effect after oral maternal exposure during organogenesis.

Science.gov (United States)

Schneider, Steffen; Kaufmann, Wolfgang; Buesen, Roland; van Ravenzwaay, Bennard

2008-04-01

The purpose of the study was to investigate a possible transgenerational effect of the fungicide vinclozolin on the male reproductive system following oral exposure since this effect was reported by Anway et al. [Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 2005;308(5727 (June 3)):1466-9] after intraperitoneal administration. Pregnant Wistar rats were dosed by oral gavage with vinclozolin 0, 4 or 100mg/(kg bw day) on days 6-15 post coitum (p.c.). F1 male offspring was mated with untreated females to produce F2, which were then similarly mated to produce F3 offspring. F0 maternal treatment had no effect on mating and fertility indices or male offspring sexual development, mean sperm parameters, or histopathology of the sexual organs in F1, F2 or F3 males (at age 127-134 days). Apoptotic germ cell counts were statistically significantly lower in F1, F2 and F3 generations, however, control values showed a pronounced variance over time. Also, as anti-androgenic compounds are more likely to induce the opposite effect (increased apoptosis), this observation is not considered to be treatment related. Consequently, spermatogenesis was not affected by vinclozolin exposure in utero. As vinclozolin has been shown to induce clear anti-androgenic effects in offspring following treatment with 100mg/(kg bw day) during entire gestation, the lack of effects in this study indicates that the window of sensitivity for anti-androgenic effects is from days 16-20 p.c. No transgenerational effect on the male reproductive system was found. The NOAEL was >100mg/(kg bw day) for fertility and reproductive performance, for systemic parental and developmental toxicity in F1, F2 and F3 males.

Transgenerational effects from early developmental exposures to bisphenol A or 17α-ethinylestradiol in medaka, Oryzias latipes

Science.gov (United States)

Bhandari, Ramji K.; vom Saal, Frederick S.; Tillitt, Donald E.

2015-01-01

The transgenerational consequences of environmental contaminant exposures of aquatic vertebrates have the potential for broad ecological impacts, yet are largely uninvestigated. Bisphenol A (BPA) and 17α-ethinylestradiol (EE2) are two ubiquitous estrogenic chemicals present in aquatic environments throughout the United States and many other countries. Aquatic organisms, including fish, are exposed to varying concentrations of these chemicals at various stages of their life history. Here, we tested the ability of embryonic exposure to BPA or EE2 to cause adverse health outcomes at later life stages and transgenerational abnormalities in medaka fish. Exposures of F0 medaka to either BPA (100 μg/L) or EE2 (0.05 μg/L) during the first 7 days of embryonic development, when germ cells are differentiating, did not cause any apparent phenotypic abnormalities in F0 or F1 generations, but led to a significant reduction in the fertilization rate in offspring two generations later (F2) as well as a reduction of embryo survival in offspring three generations later (F3). Our present observations suggest that BPA or EE2 exposure during development induces transgenerational phenotypes of reproductive impairment and compromised embryonic survival in fish of subsequent generations. These adverse outcomes may have negative impacts on populations of fish inhabiting contaminated aquatic environments.

Thermal transgenerational plasticity in natural populations of Daphnia.

Science.gov (United States)

Walsh, Matthew R; Whittington, Deirdre; Funkhouser, Collin

2014-11-01

Rising temperatures associated with global climatic change threaten the persistence of species. Determining how species adapt to environmental change is paramount. Much work has shown that environmental stressors have the potential to induce phenotypic changes that span multiple generations. Such transgenerational plasticity (TGP) represents a mechanism that may allow for rapid responses to global climatic change. Yet, our understanding of thermal TGP beyond the relationship between parent and offspring is limited. We evaluated thermal TGP in development across three generations (i.e., F0, F1, and F2) in zooplankton (Daphnia ambigua) from lakes in Connecticut. We found that the temperatures at which parents and grandparents were reared significantly influenced age at maturation in the grand-offspring. Comparisons between the F0 and F1 generation show that the offspring of parents reared at low temperatures matured significantly faster than the offspring of parents reared at a higher temperature. However, age at maturation in the grand-offspring was influenced by the interactive effects of parents and grandparents. Such an effect yielded trends that were not readily predicted from the previous generations and whose adaptive significance is unclear. Our results thus call for additional theoretical and empirical work to better understand the transgenerational effects of temperature. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy.

Science.gov (United States)

Choi, Chang Soon; Gonzales, Edson Luck; Kim, Ki Chan; Yang, Sung Min; Kim, Ji-Woon; Mabunga, Darine Froy; Cheong, Jae Hoon; Han, Seol-Heui; Bahn, Geon Ho; Shin, Chan Young

2016-11-07

Autism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder in which various genetic and environmental factors are believed to underlie its development. Recently, epigenetics has been suggested as a novel concept for ASD aetiology with a proposition that epigenetic marks can be transgenerationally inherited. Based on this assumption of epigenetics, we investigated the transgenerational inheritance of ASD-like behaviours and their related synaptic changes in the VPA animal model of ASD. The first generation (F1) VPA-exposed offspring exhibited autistic-like impaired sociability and increased marble burying. They also showed increased seizure susceptibility, hyperactivity and decreased anxiety. We mated the VPA-exposed F1 male offspring with naïve females to produce the second generation (F2), and then similarly mated the F2 to deliver the third generation (F3). Remarkably, the autism-like behavioural phenotypes found in F1 persisted to the F2 and F3. Additionally, the frontal cortices of F1 and F3 showed some imbalanced expressions of excitatory/inhibitory synaptic markers, suggesting a transgenerational epigenetic inheritance. These results open the idea that E/I imbalance and ASD-like behavioural changes induced by environmental insults in mice can be epigenetically transmitted, at least, to the third generation. This study could help explain the unprecedented increase in ASD prevalence.

Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNAs.

Science.gov (United States)

Schuster, Andrew; Skinner, Michael K; Yan, Wei

Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats. Over 200 differentially expressed sncRNAs were identified and the tRNA-derived sncRNAs, namely 5' halves of mature tRNAs (5' halves), displayed the most dramatic changes. Gene targets of the altered miRNAs and tRNA 5' halves revealed associations between the altered sncRNAs and differentially DNA methylated regions. Dysregulated sncRNAs appear to correlate with mRNA profiles associated with the previously observed vinclozolin-induced disease phenotypes. Data suggest potential connections between sperm-borne RNAs and the vinclozolin-induced epigenetic transgenerational inheritance phenomenon.

Plastics derived endocrine disruptors (BPA, DEHP and DBP induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

Directory of Open Access Journals (Sweden)

Mohan Manikkam

Full Text Available Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3 following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA, bis(2-ethylhexylphthalate (DEHP and dibutyl phthalate (DBP at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.

Individual and person: The possible collapse of transgenerational

Directory of Open Access Journals (Sweden)

Corrado Pontalti

2010-06-01

Full Text Available Considering the transgenerational dimension requires to deal with "multipersonal fields" during the psychotherapeutic situation, in order make speakable the stories and collective memory. This device is especially important in therapy with children, adolescents and young adults suffering from serious psychopathological problems because the narrative capacity is reduced further and it becomes necessary to hear other witnesses and narrators of the family scene.In human culture, the transgenerational has always had that enormous therapeutic power of storytelling that creates connections to the passing of eras, such as myths and fairy tales.As we are taught by anthropological sciences in the last 150 years occurred substantial cultural changes: the life stories are no longer fixed in a territorial unit within conservative culture with stable and ancestral myths organizers of social, but we are all moving between migration and displacement, and this determines a distance from the community places where the transgenerational has been staged and formed our primitive root of identity. The story of this migration has to do with the construction of the mind.These issues are developed through the description of a clinical case where the adoption of a multipersonal therapeutic field can resume ancestral traces of these cultural objects hidden and become tellable.

Transgenerational effects of ocean warming on the sea urchin Strongylocentrotus intermedius.

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Zhao, Chong; Zhang, Lisheng; Shi, Dongtao; Ding, Jingyun; Yin, Donghong; Sun, Jiangnan; Zhang, Baojing; Zhang, Lingling; Chang, Yaqing

2018-04-30

Transgenerational effects, which involve both selection and plasticity, are important for the evolutionary adaptation of echinoderms in the changing ocean. Here, we investigated the effects of breeding design and water temperature for offspring on fertilization, hatchability, larval survival, size, abnormality and metamorphosis of the sea urchin Strongylocentrotus intermedius, whose dams and sires were exposed to long-term (~15 months) elevated temperature (~3°C above ambient) or ambient temperature. There was no transgenerational effect on fertilization and metamorphosis of S. intermedius, while negative transgenerational effects were found in hatchability and most traits of larval size. Dam and sire effects were highly trait and developmental stage dependent. Interestingly, we found S. intermedius probably cannot achieve transgenerational acclimation to long-term elevated temperature for survival provided their offspring were exposed to an elevated temperature. The present study enriches our understanding of transgenerational effects of ocean warming on sea urchins. Copyright © 2018 Elsevier Inc. All rights reserved.

Adaptive transgenerational plasticity in plants: case studies, mechanisms, and implications for natural populations

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Jacob J. Herman

2011-12-01

Full Text Available Plants respond to environmental conditions not only by plastic changes to their own development and physiology, but also by altering the phenotypes expressed by their offspring. This transgenerational plasticity was initially considered to entail only negative effects of stressful parental environments, such as production of smaller seeds by resource- or temperature-stressed parent plants, and was therefore viewed as environmental noise. Recent evolutionary ecology studies have shown that in some cases, these inherited environmental effects can include specific growth adjustments that are functionally adaptive to the parental conditions that induced them, which can range from contrasting states of controlled laboratory environments to the complex habitat variation encountered by natural plant populations. Preliminary findings suggest that adaptive transgenerational effects can be transmitted by means of diverse mechanisms including changes to seed provisioning and biochemistry, and epigenetic modifications such as DNA methylation that can persist across multiple generations. These non-genetically inherited adaptations can influence the ecological breadth and evolutionary dynamics of plant taxa and promote the spread of invasive plants. Interdisciplinary studies that join mechanistic and evolutionary ecology approaches will be an important source of future insights.

Adaptive transgenerational plasticity in plants: case studies, mechanisms, and implications for natural populations.

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Herman, Jacob J; Sultan, Sonia E

2011-01-01

Plants respond to environmental conditions not only by plastic changes to their own development and physiology, but also by altering the phenotypes expressed by their offspring. This transgenerational plasticity was initially considered to entail only negative effects of stressful parental environments, such as production of smaller seeds by resource- or temperature-stressed parent plants, and was therefore viewed as environmental noise. Recent evolutionary ecology studies have shown that in some cases, these inherited environmental effects can include specific growth adjustments that are functionally adaptive to the parental conditions that induced them, which can range from contrasting states of controlled laboratory environments to the complex habitat variation encountered by natural plant populations. Preliminary findings suggest that adaptive transgenerational effects can be transmitted by means of diverse mechanisms including changes to seed provisioning and biochemistry, and epigenetic modifications such as DNA methylation that can persist across multiple generations. These non-genetically inherited adaptations can influence the ecological breadth and evolutionary dynamics of plant taxa and promote the spread of invasive plants. Interdisciplinary studies that join mechanistic and evolutionary ecology approaches will be an important source of future insights.

Offspring reaction norms shaped by parental environment: interaction between within- and trans-generational plasticity of inducible defenses.

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Luquet, Emilien; Tariel, Juliette

2016-10-12

Within-generational plasticity (WGP) and transgenerational plasticity (TGP) are mechanisms allowing rapid adaptive responses to fluctuating environments without genetic change. These forms of plasticity have often been viewed as independent processes. Recent evidence suggests that WGP is altered by the environmental conditions experienced by previous generations (i.e., TGP). In the context of inducible defenses, one of the most studied cases of plasticity, the WGP x TGP interaction has been poorly investigated. We provide evidence that TGP can alter the reaction norms of inducible defenses in a freshwater snail. The WGP x TGP interaction patterns are trait-specific and lead to decreased slope of reaction norms (behaviour and shell thickness). Offspring from induced parents showed a higher predator avoidance behaviour and a thicker shell than snails from non-induced parents in no predator-cue environment while they reached similar defenses in predator-cue environment. The WGP x TGP interaction further lead to a switch from a plastic towards a constitutive expression of defenses for shell dimensions (flat reaction norm). WGP-alteration by TGP may shape the adaptive responses to environmental change and then has a substantial importance to understand the evolution of plasticity.

The importance of trans-generational effects in Lepidoptera

OpenAIRE

Woestmann, Luisa; Saastamoinen, Marjo

2016-01-01

The importance of trans-generational effects in shaping an individuals' phenotype and fitness, and consequently even impacting population dynamics is increasingly apparent. Most of the research on trans-generational effects still focuses on plants, mammals, and birds. In the past few years, however, increasing number of studies, especially on maternal effects, have highlighted their importance also in many insect systems. Lepidoptera, specifically butterflies, have been used as model systems ...

Understanding the transgenerational orientation of family businesses: the role of family governance and business family identity

OpenAIRE

Süss-Reyes, Julia

2017-01-01

The development of a transgenerational orientation is one of the most significant challenges that family businesses face and only a small number actually survive across generations. While prior research has focused on the business unit to provide us with a solid understanding of how corporate governance affects business performance and continuity, the role of the business family in the development of a transgenerational orientation has received less attention. To address this g...

Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease.

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Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K

2008-05-01

Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1-F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8-E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1-F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1-F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states.

Heat priming induces trans-generational tolerance to high temperature stress in wheat

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Xiao eWang

2016-04-01

Full Text Available Wheat plants are very sensitive to high temperature stress during grain filling. Effects of heat priming applied to the first generation on tolerance of the successive generation to post-anthesis high temperature stress were investigated. Compared with the progeny of non-heat primed plants (NH, the progeny of heat-primed plants (PH possessed higher grain yield, leaf photosynthesis and activities of antioxidant enzymes and lower cell membrane damage under high temperature stress. In the transcriptome profile, 1430 probes showed obvious difference in expression between PH and NH. These genes were related to signal transduction, transcription, energy, defense, and protein destination and storage, respectively. The gene encoding the lysine-specific histone demethylase 1 (LSD1 which was involved in histone demethylation related to epigenetic modification was up-regulated in the PH compared with NH. The proteome analysis indicated that the proteins involved in photosynthesis, energy production and protein destination and storage were up-regulated in the PH compared with NH. In short, thermos-tolerance was induced through heritable epigenetic alternation and signaling transduction, both processes further triggered prompt modifications of defense related responses in anti-oxidation, transcription, energy production, and protein destination and storage in the progeny of the primed plants under high temperature stress. It was concluded that trans-generation thermo-tolerance was induced by heat priming in the first generation, and this might be an effective measure to cope with severe high-temperature stresses during key growth stages in wheat production.

Transgenerational epigenetics of parental exposure to ionising radiation and other mutagens

International Nuclear Information System (INIS)

Dubrova, Yuri E.

2013-01-01

Recent studies have established that epigenetic changes play an important role in many common human diseases, including cancer. Given that the epigenetic landscape of the mammalian cell is not fixed and undergoes massive reprogramming during development, it can potentially be affected by a variety of environmental factors. As the majority of the de novo epigenetic marks, including DNA methylation, are faithfully reproduced during DNA replication, they are transmissible through many cell divisions and, in some cases, can be passed from parents to their offspring. An increasing body of experimental evidence from animal and human studies suggests that environmentally-induced epigenetic changes can be inherited by subsequent generations and can result in transgenerational phenotypic alterations, including predisposition to common diseases

Intra- and trans-generational costs of reduced female body size caused by food limitation early in life in mites.

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Andreas Walzer

Full Text Available Food limitation early in life may be compensated for by developmental plasticity resulting in accelerated development enhancing survival at the expense of small adult body size. However and especially for females in non-matching maternal and offspring environments, being smaller than the standard may incur considerable intra- and trans-generational costs.Here, we evaluated the costs of small female body size induced by food limitation early in life in the sexually size-dimorphic predatory mite Phytoseiulus persimilis. Females are larger than males. These predators are adapted to exploit ephemeral spider mite prey patches. The intra- and trans-generational effects of small maternal body size manifested in lower maternal survival probabilities, decreased attractiveness for males, and a reduced number and size of eggs compared to standard-sized females. The trans-generational effects of small maternal body size were sex-specific with small mothers producing small daughters but standard-sized sons.Small female body size apparently intensified the well-known costs of sexual activity because mortality of small but not standard-sized females mainly occurred shortly after mating. The disadvantages of small females in mating and egg production may be generally explained by size-associated morphological and physiological constraints. Additionally, size-assortative mate preferences of standard-sized mates may have rendered small females disproportionally unattractive mating partners. We argue that the sex-specific trans-generational effects were due to sexual size dimorphism - females are the larger sex and thus more strongly affected by maternal stress than the smaller males - and to sexually selected lower plasticity of male body size.

Intra- and trans-generational costs of reduced female body size caused by food limitation early in life in mites.

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Walzer, Andreas; Schausberger, Peter

2013-01-01

Food limitation early in life may be compensated for by developmental plasticity resulting in accelerated development enhancing survival at the expense of small adult body size. However and especially for females in non-matching maternal and offspring environments, being smaller than the standard may incur considerable intra- and trans-generational costs. Here, we evaluated the costs of small female body size induced by food limitation early in life in the sexually size-dimorphic predatory mite Phytoseiulus persimilis. Females are larger than males. These predators are adapted to exploit ephemeral spider mite prey patches. The intra- and trans-generational effects of small maternal body size manifested in lower maternal survival probabilities, decreased attractiveness for males, and a reduced number and size of eggs compared to standard-sized females. The trans-generational effects of small maternal body size were sex-specific with small mothers producing small daughters but standard-sized sons. Small female body size apparently intensified the well-known costs of sexual activity because mortality of small but not standard-sized females mainly occurred shortly after mating. The disadvantages of small females in mating and egg production may be generally explained by size-associated morphological and physiological constraints. Additionally, size-assortative mate preferences of standard-sized mates may have rendered small females disproportionally unattractive mating partners. We argue that the sex-specific trans-generational effects were due to sexual size dimorphism - females are the larger sex and thus more strongly affected by maternal stress than the smaller males - and to sexually selected lower plasticity of male body size.

Bulimia: The Transgenerational View.

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Roberto, Laura Giat

1986-01-01

Within families with bulimia, certain interactional patterns enable and perpetuate the patient's binge-eating and purging symptoms. A transgenerational treatment method is proposed, which intervenes in ongoing dysfunctional patterns, and provides a frame for creating a therapeutic metaphor ("legacy") to direct the therapy. Rationale and stages of…

Direct but no transgenerational effects of decitabine and vorinostat on male fertility.

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Ruth Kläver

Full Text Available Establishment and maintenance of the correct epigenetic code is essential for a plethora of physiological pathways and disturbed epigenetic patterns can provoke severe consequences, e.g. tumour formation. In recent years, epigenetic drugs altering the epigenome of tumours actively have been developed for anti-cancer therapies. However, such drugs could potentially also affect other physiological pathways and systems in which intact epigenetic patterns are essential. Amongst those, male fertility is one of the most prominent. Consequently, we addressed possible direct effects of two epigenetic drugs, decitabine and vorinostat, on both, the male germ line and fertility. In addition, we checked for putative transgenerational epigenetic effects on the germ line of subsequent generations (F1-F3. Parental adult male C57Bl/6 mice were treated with either decitabine or vorinostat and analysed as well as three subsequent untreated generations derived from these males. Treatment directly affected several reproductive parameters as testis (decitabine & vorinostat and epididymis weight, size of accessory sex glands (vorinostat, the height of the seminiferous epithelium and sperm concentration and morphology (decitabine. Furthermore, after decitabine administration, DNA methylation of a number of loci was altered in sperm. However, when analysing fertility of treated mice (fertilisation, litter size and sex ratio, no major effect of the selected epigenetic drugs on male fertility was detected. In subsequent generations (F1-F3 generations only subtle changes on reproductive organs, sperm parameters and DNA methylation but no overall effect on fertility was observed. Consequently, in mice, decitabine and vorinostat neither affected male fertility per se nor caused marked transgenerational effects. We therefore suggest that both drugs do not induce major adverse effects-in terms of male fertility and transgenerational epigenetic inheritance-when used in anti-cancer-therapies.

Direct but no transgenerational effects of decitabine and vorinostat on male fertility.

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Kläver, Ruth; Sánchez, Victoria; Damm, Oliver S; Redmann, Klaus; Lahrmann, Elisabeth; Sandhowe-Klaverkamp, Reinhild; Rohde, Christian; Wistuba, Joachim; Ehmcke, Jens; Schlatt, Stefan; Gromoll, Jörg

2015-01-01

Establishment and maintenance of the correct epigenetic code is essential for a plethora of physiological pathways and disturbed epigenetic patterns can provoke severe consequences, e.g. tumour formation. In recent years, epigenetic drugs altering the epigenome of tumours actively have been developed for anti-cancer therapies. However, such drugs could potentially also affect other physiological pathways and systems in which intact epigenetic patterns are essential. Amongst those, male fertility is one of the most prominent. Consequently, we addressed possible direct effects of two epigenetic drugs, decitabine and vorinostat, on both, the male germ line and fertility. In addition, we checked for putative transgenerational epigenetic effects on the germ line of subsequent generations (F1-F3). Parental adult male C57Bl/6 mice were treated with either decitabine or vorinostat and analysed as well as three subsequent untreated generations derived from these males. Treatment directly affected several reproductive parameters as testis (decitabine & vorinostat) and epididymis weight, size of accessory sex glands (vorinostat), the height of the seminiferous epithelium and sperm concentration and morphology (decitabine). Furthermore, after decitabine administration, DNA methylation of a number of loci was altered in sperm. However, when analysing fertility of treated mice (fertilisation, litter size and sex ratio), no major effect of the selected epigenetic drugs on male fertility was detected. In subsequent generations (F1-F3 generations) only subtle changes on reproductive organs, sperm parameters and DNA methylation but no overall effect on fertility was observed. Consequently, in mice, decitabine and vorinostat neither affected male fertility per se nor caused marked transgenerational effects. We therefore suggest that both drugs do not induce major adverse effects-in terms of male fertility and transgenerational epigenetic inheritance-when used in anti-cancer-therapies.

Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease.

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Anway, Matthew D; Skinner, Michael K

2008-04-01

The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study. Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation. Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1-F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd). The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease.

Transgenerational plasticity following a dual pathogen and stress challenge in fruit flies.

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Nystrand, M; Cassidy, E J; Dowling, D K

2016-08-27

Phenotypic plasticity operates across generations, when the parental environment affects phenotypic expression in the offspring. Recent studies in invertebrates have reported transgenerational plasticity in phenotypic responses of offspring when the mothers had been previously exposed to either live or heat-killed pathogens. Understanding whether this plasticity is adaptive requires a factorial design in which both mothers and their offspring are subjected to either the pathogen challenge or a control, in experimentally matched and mismatched combinations. Most prior studies exploring the capacity for pathogen-mediated transgenerational plasticity have, however, failed to adopt such a design. Furthermore, it is currently poorly understood whether the magnitude or direction of pathogen-mediated transgenerational responses will be sensitive to environmental heterogeneity. Here, we explored the transgenerational consequences of a dual pathogen and stress challenge administered in the maternal generation in the fruit fly, Drosophila melanogaster. Prospective mothers were assigned to a non-infectious pathogen treatment consisting of an injection with heat-killed bacteria or a procedural control, and a stress treatment consisting of sleep deprivation or control. Their daughters and sons were similarly assigned to the same pathogen treatment, prior to measurement of their reproductive success. We observed transgenerational interactions involving pathogen treatments of mothers and their offspring, on the reproductive success of daughters but not sons. These interactions were unaffected by sleep deprivation. The direction of the transgenerational effects was not consistent with that predicted under a scenario of adaptive transgenerational plasticity. Instead, they were indicative of expectations based on terminal investment.

High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

DEFF Research Database (Denmark)

de Castro Barbosa, Thais; Ingerslev, Lars R; Alm, Petter S

2016-01-01

OBJECTIVES: Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring. METHODS: F0-male rats fed either HFD or chow diet......1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets. CONCLUSION: Our results provide insight...... into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations....

Intra- and Trans-Generational Costs of Reduced Female Body Size Caused by Food Limitation Early in Life in Mites

OpenAIRE

Walzer, Andreas; Schausberger, Peter

2013-01-01

Background Food limitation early in life may be compensated for by developmental plasticity resulting in accelerated development enhancing survival at the expense of small adult body size. However and especially for females in non-matching maternal and offspring environments, being smaller than the standard may incur considerable intra- and trans-generational costs. Methodology/Principal Findings Here, we evaluated the costs of small female body size induced by food limitation early in life i...

Persistence of Positive Carryover Effects in the Oyster, Saccostrea glomerata, following Transgenerational Exposure to Ocean Acidification.

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Laura M Parker

Full Text Available Ocean acidification (OA is predicted to have widespread implications for marine organisms, yet the capacity for species to acclimate or adapt over this century remains unknown. Recent transgenerational studies have shown that for some marine species, exposure of adults to OA can facilitate positive carryover effects to their larval and juvenile offspring that help them to survive in acidifying oceanic conditions. But whether these positive carryover effects can persist into adulthood or the next generation is unknown. Here we tested whether positive carryover effects found in larvae of the oyster, Saccostrea glomerata following transgenerational exposure to elevated CO2, could persist into adulthood and whether subsequent transgenerational exposure of adults to elevated CO2 would facilitate similar adaptive responses in the next generation of larvae and juveniles. Following our previous transgenerational exposure of parental adults and first generation (F1 larvae to ambient (385 μatm and elevated (856 μatm CO2, newly settled F1 juveniles were transferred to the field at ambient CO2 for 14 months, until they reached reproductive maturity. At this time, the F1 adults were returned to the laboratory and the previous transgenerational CO2 exposure was repeated to produce F2 offspring. We found that the capacity of adults to regulate extracellular pH at elevated CO2 was improved if they had a prior history of transgenerational exposure to elevated CO2. In addition, subsequent transgenerational exposure of these adults led to an increase in the resilience of their larval and juvenile offspring. Offspring with a history of transgenerational exposure to elevated CO2 had a lower percentage abnormality, faster development rate, faster shell growth and increased heart rate at elevated CO2 compared with F2 offspring with no prior history of exposure to elevated CO2. Our results suggest that positive carryover effects originating during parental and larval

Accessing Transgenerational Themes Through Dreamwork.

Science.gov (United States)

Andrews, Jennifer; And Others

1988-01-01

Proposes use of dreamwork to evoke historical patterns or transgenerational themes. Describes new variant of dreamwork which combines aspects of both gestalt and family systems therapies. Implications of therapeutic dramatization for couple therapy are suggested. Examples are included. (Author/NB)

Intra- and Trans-Generational Costs of Reduced Female Body Size Caused by Food Limitation Early in Life in Mites

Science.gov (United States)

Walzer, Andreas; Schausberger, Peter

2013-01-01

Background Food limitation early in life may be compensated for by developmental plasticity resulting in accelerated development enhancing survival at the expense of small adult body size. However and especially for females in non-matching maternal and offspring environments, being smaller than the standard may incur considerable intra- and trans-generational costs. Methodology/Principal Findings Here, we evaluated the costs of small female body size induced by food limitation early in life in the sexually size-dimorphic predatory mite Phytoseiulus persimilis. Females are larger than males. These predators are adapted to exploit ephemeral spider mite prey patches. The intra- and trans-generational effects of small maternal body size manifested in lower maternal survival probabilities, decreased attractiveness for males, and a reduced number and size of eggs compared to standard-sized females. The trans-generational effects of small maternal body size were sex-specific with small mothers producing small daughters but standard-sized sons. Conclusions/Significance Small female body size apparently intensified the well-known costs of sexual activity because mortality of small but not standard-sized females mainly occurred shortly after mating. The disadvantages of small females in mating and egg production may be generally explained by size-associated morphological and physiological constraints. Additionally, size-assortative mate preferences of standard-sized mates may have rendered small females disproportionally unattractive mating partners. We argue that the sex-specific trans-generational effects were due to sexual size dimorphism – females are the larger sex and thus more strongly affected by maternal stress than the smaller males – and to sexually selected lower plasticity of male body size. PMID:24265745

Transgenerational plasticity in Silene vulgaris in response to three types of stress.

Science.gov (United States)

Sandner, T M; van Braak, J L; Matthies, D

2018-03-23

The environment experienced by plants can influence the phenotype of their offspring. Such transgenerational plasticity can be adaptive when it results in higher fitness of the offspring under conditions correlated with those experienced by the mother plant. However, it has rarely been tested if such anticipatory parental effects may be induced with different environments. We grew clonal replicates of Silene vulgaris under control conditions and three types of stress (nutrient deficiency, copper addition and drought), which are known from natural populations of the species. We then subjected offspring from differently treated mother plants to each of the different stress treatments to analyse the influence of maternal and offspring environment on performance and several functional traits. Current stress treatments strongly influenced biomass and functional traits of the plants, mostly in line with responses predicted by the theory of functional equilibrium. Plant performance was also influenced by maternal stress treatments, and some effects independent of initial size differences remained until harvest. In particular, stressed mothers produced offspring of higher fitness than control plants. However, there was no evidence for treatment-specific adaptive transgenerational plasticity, as offspring from a mother plant that had grown in a specific environment did not grow better in that environment than other plants. Our results indicate that the maternal environment may affect offspring traits and performance, but also that this transgenerational plasticity is not necessarily adaptive. © 2018 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.

Transgenerational plasticity is adaptive in the wild.

Science.gov (United States)

Galloway, Laura F; Etterson, Julie R

2007-11-16

Plants exhibit adaptive responses to light, but it is not known whether parental plants transmit environmental cues that elicit adaptive responses in offspring. We show that offspring life history (annual versus biennial) is influenced by the maternal light environment (understory versus light gap). This transgenerational plasticity is adaptive when offspring are grown in their maternal light environment, where seeds typically disperse. Projections of population growth show that plants that are appropriately cued for their light environment through maternal effects have 3.4 times greater fitness than otherwise. Transgenerational plasticity has evolved in response to natural variation in light and provides a flexible mechanism by which sedentary organisms cope with heterogeneous environments.

Vinclozolin--no transgenerational inheritance of anti-androgenic effects after maternal exposure during organogenesis via the intraperitoneal route.

Science.gov (United States)

Schneider, Steffen; Marxfeld, Heike; Gröters, Sibylle; Buesen, Roland; van Ravenzwaay, Bennard

2013-06-01

The goal of this study was to examine the potential transgenerational inheritance of anti-androgenic effects induced by Vinclozolin administered intraperitoneally to pregnant Wistar rats (Crl:WI[Han]). Dams were dosed with Vinclozolin at 0, 4 or 100mg/kg bw/d on gestation days 6-15. Male offspring of F1-F3 generations were bred with untreated females to yield F2-F4 offspring. No evident anti-androgenic effects were observed at 4mg/kg bw/d, but a case of hypospadias as well as delayed sexual maturation in F1 male offspring was observed as a sign of anti-androgenicity at 100mg/kg bw/d. However, F1-F3 males developed normally to sexual maturity and were able to mate and to generate healthy progeny. Sperm count, morphology and motility were not affected in F1-F4 generation male offspring. In conclusion, transgenerational inheritance of Vinclozolin's anti-androgenic effects was not evident in outbred Wistar rats. Copyright © 2013 Elsevier Inc. All rights reserved.

Predator-induced phenotypic plasticity within- and across-generations: a challenge for theory?

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Walsh, Matthew R; Cooley, Frank; Biles, Kelsey; Munch, Stephan B

2015-01-07

Much work has shown that the environment can induce non-genetic changes in phenotype that span multiple generations. Theory predicts that predictable environmental variation selects for both increased within- and across-generation responses. Yet, to the best of our knowledge, there are no empirical tests of this prediction. We explored the relationship between within- versus across-generation plasticity by evaluating the influence of predator cues on the life-history traits of Daphnia ambigua. We measured the duration of predator-induced transgenerational effects, determined when transgenerational responses are induced, and quantified the cues that activate transgenerational plasticity. We show that predator exposure during embryonic development causes earlier maturation and increased reproductive output. Such effects are detectable two generations removed from predator exposure and are similar in magnitude in response to exposure to cues emitted by injured conspecifics. Moreover, all experimental contexts and traits yielded a negative correlation between within- versus across-generation responses. That is, responses to predator cues within- and across-generations were opposite in sign and magnitude. Although many models address transgenerational plasticity, none of them explain this apparent negative relationship between within- and across-generation plasticities. Our results highlight the need to refine the theory of transgenerational plasticity. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

DNA methylation mediates genetic variation for adaptive transgenerational plasticity.

Science.gov (United States)

Herman, Jacob J; Sultan, Sonia E

2016-09-14

Environmental stresses experienced by individual parents can influence offspring phenotypes in ways that enhance survival under similar conditions. Although such adaptive transgenerational plasticity is well documented, its transmission mechanisms are generally unknown. One possible mechanism is environmentally induced DNA methylation changes. We tested this hypothesis in the annual plant Polygonum persicaria, a species known to express adaptive transgenerational plasticity in response to parental drought stress. Replicate plants of 12 genetic lines (sampled from natural populations) were grown in dry versus moist soil. Their offspring were exposed to the demethylating agent zebularine or to control conditions during germination and then grown in dry soil. Under control germination conditions, the offspring of drought-stressed parents grew longer root systems and attained greater biomass compared with offspring of well-watered parents of the same genetic lines. Demethylation removed these adaptive developmental effects of parental drought, but did not significantly alter phenotypic expression in offspring of well-watered parents. The effect of demethylation on the expression of the parental drought effect varied among genetic lines. Differential seed provisioning did not contribute to the effect of parental drought on offspring phenotypes. These results demonstrate that DNA methylation can mediate adaptive, genotype-specific effects of parental stress on offspring phenotypes. © 2016 The Author(s).

Can trans-generational experiments be used to enhance species resilience to ocean warming and acidification?

Science.gov (United States)

Chakravarti, Leela J; Jarrold, Michael D; Gibbin, Emma M; Christen, Felix; Massamba-N'Siala, Gloria; Blier, Pierre U; Calosi, Piero

2016-10-01

Human-assisted, trans-generational exposure to ocean warming and acidification has been proposed as a conservation and/or restoration tool to produce resilient offspring. To improve our understanding of the need for and the efficacy of this approach, we characterized life-history and physiological responses in offspring of the marine polychaete Ophryotrocha labronica exposed to predicted ocean warming (OW: + 3°C), ocean acidification (OA: pH -0.5) and their combination (OWA: + 3°C, pH -0.5), following the exposure of their parents to either control conditions ( within-generational exposure ) or the same conditions ( trans-generational exposure ). Trans-generational exposure to OW fully alleviated the negative effects of within-generational exposure to OW on fecundity and egg volume and was accompanied by increased metabolic activity. While within-generational exposure to OA reduced juvenile growth rates and egg volume, trans-generational exposure alleviated the former but could not restore the latter. Surprisingly, exposure to OWA had no negative impacts within- or trans-generationally. Our results highlight the potential for trans-generational laboratory experiments in producing offspring that are resilient to OW and OA. However, trans-generational exposure does not always appear to improve traits and therefore may not be a universally useful tool for all species in the face of global change.

Drought-induced trans-generational tradeoff between stress tolerance and defence: consequences for range limits?

OpenAIRE

Alsdurf, Jacob D.; Ripley, Tayler J.; Matzner, Steven L.; Siemens, David H.

2013-01-01

Areas just across species range boundaries are often stressful, but even with ample genetic variation within and among range-margin populations, adaptation towards stress tolerance across range boundaries often does not occur. Adaptive trans-generational plasticity should allow organisms to circumvent these problems for temporary range expansion; however, range boundaries often persist. To investigate this dilemma, we drought stressed a parent generation of Boechera stricta (A.Gray) A. L?ve &...

Transgenerational transmission of trauma and resilience: a qualitative study with Brazilian offspring of Holocaust survivors.

Science.gov (United States)

Braga, Luciana Lorens; Mello, Marcelo Feijó; Fiks, José Paulo

2012-09-03

Over the past five decades, clinicians and researchers have debated the impact of the Holocaust on the children of its survivors. The transgenerational transmission of trauma has been explored in more than 500 articles, which have failed to reach reliable conclusions that could be generalized. The psychiatric literature shows mixed findings regarding this subject: many clinical studies reported psychopathological findings related to transgenerational transmission of trauma and some empirical research has found no evidence of this phenomenon in offspring of Holocaust survivors. This qualitative study aims to detect how the second generation perceives transgenerational transmission of their parents' experiences in the Holocaust. In-depth individual interviews were conducted with fifteen offspring of Holocaust survivors and sought to analyze experiences, meanings and subjective processes of the participants. A Grounded Theory approach was employed, and constant comparative method was used for analysis of textual data. The development of conceptual categories led to the emergence of distinct patterns of communication from parents to their descendants. The qualitative methodology also allowed systematization of the different ways in which offspring can deal with parental trauma, which determine the development of specific mechanisms of traumatic experience or resilience in the second generation. The conceptual categories constructed by the Grounded Theory approach were used to present a possible model of the transgenerational transmission of trauma, showing that not only traumatic experiences, but also resilience patterns can be transmitted to and developed by the second generation. As in all qualitative studies, these conclusions cannot be generalized, but the findings can be tested in other contexts.

Maternal corticosterone exposure has transgenerational effects on grand-offspring.

Science.gov (United States)

Khan, Nicola; Peters, Richard A; Richardson, Emily; Robert, Kylie A

2016-11-01

The hormone fluctuations that an animal experiences during ovulation can have lifelong effects on developing offspring. These hormones may act as an adaptive mechanism, allowing offspring to be 'pre-programmed' to survive in an unstable environment. Here, we used a transgenerational approach to examine the effects of elevated maternal corticosterone (CORT) on the future reproductive success of female offspring. We show that female zebra finches (Taeniopygia guttata) exposed to embryonic CORT produce daughters that have equal reproductive success (clutch sizes, fertility, hatching success) compared with the daughters produced from untreated mothers, but their offspring had accelerated post-hatching growth rates and were significantly heavier by nutritional independence. Although there was no significant effect on primary offspring sex ratio, females from CORT-treated mothers produced significantly female-biased clutches by nutritional independence. To the best of our knowledge, this is the first record of a transgenerational sex ratio bias in response to elevated maternal CORT in any avian species. © 2016 The Author(s).

Transgenerational transmission of trauma and resilience: a qualitative study with Brazilian offspring of Holocaust survivors

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Braga Luciana

2012-09-01

Full Text Available Abstract Background Over the past five decades, clinicians and researchers have debated the impact of the Holocaust on the children of its survivors. The transgenerational transmission of trauma has been explored in more than 500 articles, which have failed to reach reliable conclusions that could be generalized. The psychiatric literature shows mixed findings regarding this subject: many clinical studies reported psychopathological findings related to transgenerational transmission of trauma and some empirical research has found no evidence of this phenomenon in offspring of Holocaust survivors. Method This qualitative study aims to detect how the second generation perceives transgenerational transmission of their parents’ experiences in the Holocaust. In-depth individual interviews were conducted with fifteen offspring of Holocaust survivors and sought to analyze experiences, meanings and subjective processes of the participants. A Grounded Theory approach was employed, and constant comparative method was used for analysis of textual data. Results The development of conceptual categories led to the emergence of distinct patterns of communication from parents to their descendants. The qualitative methodology also allowed systematization of the different ways in which offspring can deal with parental trauma, which determine the development of specific mechanisms of traumatic experience or resilience in the second generation. Conclusions The conceptual categories constructed by the Grounded Theory approach were used to present a possible model of the transgenerational transmission of trauma, showing that not only traumatic experiences, but also resilience patterns can be transmitted to and developed by the second generation. As in all qualitative studies, these conclusions cannot be generalized, but the findings can be tested in other contexts.

Rapid transcriptional acclimation following transgenerational exposure of oysters to ocean acidification.

Science.gov (United States)

Goncalves, Priscila; Anderson, Kelli; Thompson, Emma L; Melwani, Aroon; Parker, Laura M; Ross, Pauline M; Raftos, David A

2016-10-01

Marine organisms need to adapt in order to cope with the adverse effects of ocean acidification and warming. Transgenerational exposure to CO2 stress has been shown to enhance resilience to ocean acidification in offspring from a number of species. However, the molecular basis underlying such adaptive responses is currently unknown. Here, we compared the transcriptional profiles of two genetically distinct oyster breeding lines following transgenerational exposure to elevated CO2 in order to explore the molecular basis of acclimation or adaptation to ocean acidification in these organisms. The expression of key target genes associated with antioxidant defence, metabolism and the cytoskeleton was assessed in oysters exposed to elevated CO2 over three consecutive generations. This set of target genes was chosen specifically to test whether altered responsiveness of intracellular stress mechanisms contributes to the differential acclimation of oyster populations to climate stressors. Transgenerational exposure to elevated CO2 resulted in changes to both basal and inducible expression of those key target genes (e.g. ecSOD, catalase and peroxiredoxin 6), particularly in oysters derived from the disease-resistant, fast-growing B2 line. Exposure to CO2 stress over consecutive generations produced opposite and less evident effects on transcription in a second population that was derived from wild-type (nonselected) oysters. The analysis of key target genes revealed that the acute responses of oysters to CO2 stress appear to be affected by population-specific genetic and/or phenotypic traits and by the CO2 conditions to which their parents had been exposed. This supports the contention that the capacity for heritable change in response to ocean acidification varies between oyster breeding lines and is mediated by parental conditioning. © 2016 John Wiley & Sons Ltd.

Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance.

Science.gov (United States)

Gonzalez-Bulnes, Antonio; Astiz, Susana; Ovilo, Cristina; Lopez-Bote, Clemente J; Sanchez-Sanchez, Raul; Perez-Solana, Maria L; Torres-Rovira, Laura; Ayuso, Miriam; Gonzalez, Jorge

2014-10-01

Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre- and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity. © 2014 Society for Endocrinology.

Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice

International Nuclear Information System (INIS)

Pocar, Paola; Fiandanese, Nadia; Berrini, Anna; Secchi, Camillo; Borromeo, Vitaliano

2017-01-01

Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. • DEHP

Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice

Energy Technology Data Exchange (ETDEWEB)

Pocar, Paola, E-mail: paola.pocar@unimi.it; Fiandanese, Nadia; Berrini, Anna; Secchi, Camillo; Borromeo, Vitaliano

2017-05-01

Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. • DEHP

Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects

Science.gov (United States)

Morgan, William F.

2003-01-01

The goal of this review is to summarize the evidence for non-targeted and delayed effects of exposure to ionizing radiation in vivo. Currently, human health risks associated with radiation exposures are based primarily on the assumption that the detrimental effects of radiation occur in irradiated cells. Over the years a number of non-targeted effects of radiation exposure in vivo have been described that challenge this concept. These include radiation-induced genomic instability, bystander effects, clastogenic factors produced in plasma from irradiated individuals that can cause chromosomal damage when cultured with nonirradiated cells, and transgenerational effects of parental irradiation that can manifest in the progeny. These effects pose new challenges to evaluating the risk(s) associated with radiation exposure and understanding radiation-induced carcinogenesis.

Transgenerational plasticity of reproduction depends on rate of warming across generations.

Science.gov (United States)

Donelson, Jennifer M; Wong, Marian; Booth, David J; Munday, Philip L

2016-10-01

Predicting the impacts of climate change to biological systems requires an understanding of the ability for species to acclimate to the projected environmental change through phenotypic plasticity. Determining the effects of higher temperatures on individual performance is made more complex by the potential for environmental conditions experienced in previous and current generations to independently affect phenotypic responses to high temperatures. We used a model coral reef fish ( Acanthochromis polyacanthus ) to investigate the influence of thermal conditions experienced by two generations on reproductive output and the quality of offspring produced by adults. We found that more gradual warming over two generations, +1.5°C in the first generation and then +3.0°C in the second generation, resulted in greater plasticity of reproductive attributes, compared to fish that experienced the same increase in one generation. Reproduction ceased at the projected future summer temperature (31.5°C) when fish experienced +3.0°C for two generations. Additionally, we found that transgenerational plasticity to +1.5°C induced full restoration of thermally affected reproductive and offspring attributes, which was not possible with developmental plasticity alone. Our results suggest that transgenerational effects differ depending on the absolute thermal change and in which life stage the thermal change is experienced.

Direct and trans-generational effects of male and female gut microbiota in Drosophila melanogaster.

Science.gov (United States)

Morimoto, Juliano; Simpson, Stephen J; Ponton, Fleur

2017-07-01

There is increasing evidence of the far-reaching effects of gut bacteria on physiological and behavioural traits, yet the fitness-related consequences of changes in the gut bacteria composition of sexually interacting individuals remain unknown. To address this question, we manipulated the gut microbiota of fruit flies, Drosophila melanogaster , by monoinfecting flies with either Acetobacter pomorum ( AP ) or Lactobacillus plantarum ( LP ) . Re-inoculated individuals were paired in all treatment combinations. LP- infected males had longer mating duration and induced higher short-term offspring production in females compared with AP -infected males. Furthermore, females of either re-inoculation state mated with AP- infected males were more likely to have zero offspring after mating, suggesting a negative effect of AP on male fertility . Finally, we found that the effects of male and female gut bacteria interacted to modulate their daughters', but not sons' body mass, revealing a new trans-generational effect of parental gut microbiota. In conclusion, this study shows direct and trans-generational effects of the gut microbiota on mating and reproduction. © 2017 The Authors.

Transgenerational deleterious effects of ocean acidification on the reproductive success of a keystone crustacean (Gammarus locusta).

Science.gov (United States)

Borges, Francisco O; Figueiredo, Cátia; Sampaio, Eduardo; Rosa, Rui; Grilo, Tiago F

2018-07-01

Ocean acidification (OA) poses a global threat to marine biodiversity. Notwithstanding, marine organisms may maintain their performance under future OA conditions, either through acclimation or evolutionary adaptation. Surprisingly, the transgenerational effects of high CO 2 exposure in crustaceans are still poorly understood. For the first time, the present study investigated the transgenerational effect of OA, from hatching to maturity, of a key amphipod species (Gammarus locusta). Negative transgenerational effects were observed on survival of the acidified lineage, resulting in significant declines (10-15%) compared to the control groups in each generation. Mate-guarding duration was also significantly reduced under high CO 2 and this effect was not alleviated by transgenerational acclimation, indicating that precopulatory behaviours can be disturbed under a future high CO 2 scenario. Although OA may initially stimulate female investment, transgenerational exposure led to a general decline in egg number and fecundity. Overall, the present findings suggest a potential fitness reduction of natural populations of G. locusta in a future high CO 2 ocean, emphasizing the need of management tools towards species' sustainability. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adaptive transgenerational plasticity in an annual plant: grandparental and parental drought stress enhance performance of seedlings in dry soil.

Science.gov (United States)

Herman, Jacob J; Sultan, Sonia E; Horgan-Kobelski, Tim; Riggs, Charlotte

2012-07-01

Stressful parental (usually maternal) environments can dramatically influence expression of traits in offspring, in some cases resulting in phenotypes that are adaptive to the inducing stress. The ecological and evolutionary impact of such transgenerational plasticity depends on both its persistence across generations and its adaptive value. Few studies have examined both aspects of transgenerational plasticity within a given system. Here we report the results of a growth-chamber study of adaptive transgenerational plasticity across two generations, using the widespread annual plant Polygonum persicaria as a naturally evolved model system. We grew five inbred Polygonum genetic lines in controlled dry vs. moist soil environments for two generations in a fully factorial design, producing replicate individuals of each genetic line with all permutations of grandparental and parental environment. We then measured the effects of these two-generational stress histories on traits critical for functioning in dry soil, in a third (grandchild) generation of seedling offspring raised in the dry treatment. Both grandparental and parental moisture environment significantly influenced seedling development: seedlings of drought-stressed grandparents or parents produced longer root systems that extended deeper and faster into dry soil compared with seedlings of the same genetic lines whose grandparents and/or parents had been amply watered. Offspring of stressed individuals also grew to a greater biomass than offspring of nonstressed parents and grandparents. Importantly, the effects of drought were cumulative over the course of two generations: when both grandparents and parents were drought-stressed, offspring had the greatest provisioning, germinated earliest, and developed into the largest seedlings with the most extensive root systems. Along with these functionally appropriate developmental effects, seedlings produced after two previous drought-stressed generations had

Trans?generational plasticity in response to immune challenge is constrained by heat stress

OpenAIRE

Roth, Olivia; Landis, Susanne H.

2017-01-01

Trans-generational plasticity is the adjustment of phenotypes to changing habitat conditions that persist longer than the individual lifetime. Fitness benefits (adaptive TGP) are expected upon matching parent-offspring environments. In a global change scenario, several performance-related environmental factors are changing simultaneously. This lowers the predictability of offspring environmental conditions, potentially hampering the benefits of trans-generational plasticity. For the first tim...

Ancestral diet leads to dynamic transgenerational plasticity for five generations in Drosophila melanogaster

OpenAIRE

Mikheyev, Alexander; Emborski, Carmen

2018-01-01

Ancestral exposures can influence phenotypic expression in subsequent generations, which influence diverse biological processes ranging from phenotypic plasticity to obesity. Currently, most transgenerational studies work under the assumption of transgenerational response stability and reproducibility through time and across exposure differences, relying on short-term (i.e. 2-3 generations) single-exposure experiments. Yet, little evidence exists in the literature to validate this assumption,...

The epigenetic landscape of transgenerational acclimation to ocean warming

KAUST Repository

Ryu, Tae Woo; Veilleux, Heather D.; Donelson, Jennifer M.; Munday, Philip L.; Ravasi, Timothy

2018-01-01

Epigenetic inheritance is a potential mechanism by which the environment in one generation can influence the performance of future generations1. Rapid climate change threatens the survival of many organisms; however, recent studies show that some species can adjust to climate-related stress when both parents and their offspring experience the same environmental change2,3. Whether such transgenerational acclimation could have an epigenetic basis is unknown. Here, by sequencing the liver genome, methylomes and transcriptomes of the coral reef fish, Acanthochromis polyacanthus, exposed to current day (+0 °C) or future ocean temperatures (+3 °C) for one generation, two generations and incrementally across generations, we identified 2,467 differentially methylated regions (DMRs) and 1,870 associated genes that respond to higher temperatures within and between generations. Of these genes, 193 were significantly correlated to the transgenerationally acclimating phenotypic trait, aerobic scope, with functions in insulin response, energy homeostasis, mitochondrial activity, oxygen consumption and angiogenesis. These genes may therefore play a key role in restoring performance across generations in fish exposed to increased temperatures associated with climate change. Our study is the first to demonstrate a possible association between DNA methylation and transgenerational acclimation to climate change in a vertebrate.

The epigenetic landscape of transgenerational acclimation to ocean warming

KAUST Repository

Ryu, Tae Woo

2018-04-26

Epigenetic inheritance is a potential mechanism by which the environment in one generation can influence the performance of future generations1. Rapid climate change threatens the survival of many organisms; however, recent studies show that some species can adjust to climate-related stress when both parents and their offspring experience the same environmental change2,3. Whether such transgenerational acclimation could have an epigenetic basis is unknown. Here, by sequencing the liver genome, methylomes and transcriptomes of the coral reef fish, Acanthochromis polyacanthus, exposed to current day (+0 °C) or future ocean temperatures (+3 °C) for one generation, two generations and incrementally across generations, we identified 2,467 differentially methylated regions (DMRs) and 1,870 associated genes that respond to higher temperatures within and between generations. Of these genes, 193 were significantly correlated to the transgenerationally acclimating phenotypic trait, aerobic scope, with functions in insulin response, energy homeostasis, mitochondrial activity, oxygen consumption and angiogenesis. These genes may therefore play a key role in restoring performance across generations in fish exposed to increased temperatures associated with climate change. Our study is the first to demonstrate a possible association between DNA methylation and transgenerational acclimation to climate change in a vertebrate.

The placental gateway of maternal transgenerational epigenetic ...

Indian Academy of Sciences (India)

While much of our understanding of genetic inheritance is based on the genome of the organism, it is becoming clear that there is an ample amount of epigenetic inheritance, which though reversible, escapes erasing process during gametogenesis and goes on to the next generation. Several examples of transgenerational ...

What role does heritability play in transgenerational phenotypic responses to captivity? Implications for managing captive populations.

Science.gov (United States)

Courtney Jones, Stephanie K; Byrne, Phillip G

2017-12-01

Animals maintained in captivity exhibit rapid changes in phenotypic traits, which may be maladaptive for natural environments. The phenotype can shift away from the wild phenotype via transgenerational effects, with the environment experienced by parents influencing the phenotype and fitness of offspring. There is emerging evidence that controlling transgenerational effects could help mitigate the effects of captivity, improving the success of captively bred animals post release. However, controlling transgenerational effects requires knowledge of the mechanisms driving transgenerational changes. To better understand the genetic mechanisms that contribute to transgenerational effects in captivity we investigated the heritability of behavioral phenotypes using mid parent- and single parent-offspring regressions in a population of captive-reared house mouse (Mus musculus) that we had previously shown exhibit transgenerational changes in boldness and activity behavioral types. Slopes for boldness and activity were all positive, indicating a low to moderate degree of heritability. Though, none of the heritability estimates were statistically significant due to the large surrounding errors. However, the large error surrounding the heritability estimates may also indicate that there is variability in heritability between behavioral traits within the boldness and activity behavioral types. The implication of this finding is that the potential for heritable genetic changes in captivity varies considerably between traits. We conclude that continued investigation of the potential for traits to evolve in captivity is needed to better inform captive breeding and reintroduction programs. © 2017 Wiley Periodicals, Inc.

Parental effects of endocrine disrupting compounds in aquatic wildlife: Is there evidence of transgenerational inheritance?

Science.gov (United States)

Schwindt, Adam R

2015-08-01

The effects of endocrine disrupting compounds (EDCs) on aquatic wildlife are increasingly being recognized for their complexity. Investigators have detected alterations at multiple levels of biological organization in offspring exposed to EDCs through the blood or germ line of the parents, suggesting that generational consequences of EDCs are evident. Exposure to EDCs through the parents is concerning because if the resulting phenotype of the offspring is heritable and affects fitness, then evolutionary consequences may be evident. This review summarizes the evidence for transgenerational effects of EDCs in aquatic wildlife and illustrates cases where alterations appear to be transmitted maternally, paternally, or parentally. The literature indicates that EDC exposure to the parents induces developmental, physiological, endocrinological, and behavioral changes as well as increased mortality of offspring raised in clean environments. What is lacking, however, is a clear demonstration of heritable transgenerational effects in aquatic wildlife. Therefore, it is not known if the parental effects are the result of developmental or phenotypic plasticity or if the altered phenotypes are durably passed to subsequent generations. Epigenetic changes to gene regulation are discussed as a possible mechanism responsible for EDC induced parental effects. Additional research is needed to evaluate if heritable effects of EDCs are evident in aquatic wildlife, as has been demonstrated for terrestrial mammals. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis

OpenAIRE

Anway, Matthew D.; Rekow, Stephen S.; Skinner, Michael K.

2008-01-01

Exposure of gestating female rats to the anti-androgenic endocrine disruptor vinclozolin has been shown to induce transgenerational adult onset disease phenotypes. The current study, was designed to compare the actions of vinclozolin to the known anti-androgenic compound flutamide. The gestating female rats were exposed to intraperitoneal injections during embryonic day 8–14 (E8–E14) to 100 mg/kg/day vinclozolin or flutamide at either 5mg or 20 mg/kg/day. As previously observed, vinclozolin i...

Germ Cell Origins of Posttraumatic Stress Disorder Risk: The Transgenerational Impact of Parental Stress Experience.

Science.gov (United States)

Rodgers, Ali B; Bale, Tracy L

2015-09-01

Altered stress reactivity is a predominant feature of posttraumatic stress disorder (PTSD) and may reflect disease vulnerability, increasing the probability that an individual will develop PTSD following trauma exposure. Environmental factors, particularly prior stress history, contribute to the developmental programming of the hypothalamic-pituitary-adrenal stress axis. Critically, the consequences of stress experiences are transgenerational, with parental stress exposure impacting stress reactivity and PTSD risk in subsequent generations. Potential molecular mechanisms underlying this transmission have been explored in rodent models that specifically examine the paternal lineage, identifying epigenetic signatures in male germ cells as possible substrates of transgenerational programming. Here, we review the role of these germ cell epigenetic marks, including posttranslational histone modifications, DNA methylation, and populations of small noncoding RNAs, in the development of offspring stress axis sensitivity and disease risk. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice.

Science.gov (United States)

Nguyen, Nguyen M; de Oliveira Andrade, Fabia; Jin, Lu; Zhang, Xiyuan; Macon, Madisa; Cruz, M Idalia; Benitez, Carlos; Wehrenberg, Bryan; Yin, Chao; Wang, Xiao; Xuan, Jianhua; de Assis, Sonia; Hilakivi-Clarke, Leena

2017-07-03

Maternal and paternal high-fat (HF) diet intake before and/or during pregnancy increases mammary cancer risk in several preclinical models. We studied if maternal consumption of a HF diet that began at a time when the fetal primordial germ cells travel to the genital ridge and start differentiating into germ cells would result in a transgenerational inheritance of increased mammary cancer risk. Pregnant C57BL/6NTac mouse dams were fed either a control AIN93G or isocaloric HF diet composed of corn oil high in n-6 polyunsaturated fatty acids between gestational days 10 and 20. Offspring in subsequent F1-F3 generations were fed only the control diet. Mammary tumor incidence induced by 7,12-dimethylbenz[a]anthracene was significantly higher in F1 (p pregnancy induces a transgenerational increase in offspring mammary cancer risk in mice. The mechanisms of inheritance in the F3 generation may be different from the F1 generation because significantly more changes were seen in the transcriptome.

Gene transcription profiles, global DNA methylation and potential transgenerational epigenetic effects related to Zn exposure history in Daphnia magna

International Nuclear Information System (INIS)

Vandegehuchte, Michiel B.; De Coninck, Dieter; Vandenbrouck, Tine; De Coen, Wim M.; Janssen, Colin R.

2010-01-01

A reduced level of DNA methylation has recently been described in both Zn-exposed and non-exposed offspring of Daphnia magna exposed to Zn. The hypothesis examined in this study is that DNA hypomethylation has an effect on gene transcription. A second hypothesis is that accumulative epigenetic effects can affect gene transcription in non-exposed offspring from parents with an exposure history of more than one generation. Transcriptional gene regulation was studied with a cDNA microarray. In the exposed and non-exposed hypomethylated daphnids, a large proportion of common genes were similarly up- or down-regulated, indicating a possible effect of the DNA hypomethylation. Two of these genes can be mechanistically involved in DNA methylation reduction. The similar transcriptional regulation of two and three genes in the F 0 and F 1 exposed daphnids on one hand and their non-exposed offspring on the other hand, could be the result of a one-generation temporary transgenerational epigenetic effect, which was not accumulative. - Zn-induced DNA hypomethylation is related to gene transcription in Daphnia magna and Zn exposure potentially induced limited temporary transgenerational effects on gene transcription.

Transgenerational epigenetics and environmental justice.

Science.gov (United States)

Rothstein, Mark A; Harrell, Heather L; Marchant, Gary E

2017-07-01

Human transmission to offspring and future generations of acquired epigenetic modifications has not been definitively established, although there are several environmental exposures with suggestive evidence. This article uses three examples of hazardous substances with greater exposures in vulnerable populations: pesticides, lead, and diesel exhaust. It then considers whether, if there were scientific evidence of transgenerational epigenetic inheritance, there would be greater attention given to concerns about environmental justice in environmental laws, regulations, and policies at all levels of government. To provide a broader perspective on environmental justice the article discusses two of the most commonly cited approaches to environmental justice. John Rawls's theory of justice as fairness, a form of egalitarianism, is frequently invoked for the principle that differential treatment of individuals is justified only if actions are designed to benefit those with the greatest need. Another theory, the capabilities approach of Amartya Sen and Martha Nussbaum, focuses on whether essential capabilities of society, such as life and health, are made available to all individuals. In applying principles of environmental justice the article considers whether there is a heightened societal obligation to protect the most vulnerable individuals from hazardous exposures that could adversely affect their offspring through epigenetic mechanisms. It concludes that unless there were compelling evidence of transgenerational epigenetic harms, it is unlikely that there would be a significant impetus to adopt new policies to prevent epigenetic harms by invoking principles of environmental justice.

Transgenerational plasticity as an important mechanism affecting response of clonal species to changing climate

OpenAIRE

M?nzbergov?, Zuzana; Hadincov?, V?roslava

2017-01-01

Abstract In spite of the increasing number of studies on the importance of transgenerational plasticity for species response to novel environments, its effects on species ability to respond to climate change are still largely unexplored. We study the importance of transgenerational plasticity for response of a clonal species Festuca rubra. Individuals from four natural populations representing two levels of temperature and two levels of precipitation were cultivated in four growth chambers th...

Human and animal evidence of potential transgenerational inheritance of health effects: An evidence map and state-of-the-science evaluation.

Science.gov (United States)

Walker, Vickie R; Boyles, Abee L; Pelch, Katherine E; Holmgren, Stephanie D; Shapiro, Andrew J; Blystone, Chad R; Devito, Michael J; Newbold, Retha R; Blain, Robyn; Hartman, Pamela; Thayer, Kristina A; Rooney, Andrew A

2018-06-01

An increasing number of reports suggest early life exposures result in adverse effects in offspring who were never directly exposed; this phenomenon is termed "transgenerational inheritance." Given concern for public health implications for potential effects of exposures transmitted to subsequent generations, it is critical to determine how widespread and robust this phenomenon is and to identify the range of exposures and possible outcomes. This scoping report examines the evidence for transgenerational inheritance associated with exposure to a wide range of stressors in humans and animals to identify areas of consistency, uncertainty, data gaps, and to evaluate general risk of bias issues for the transgenerational study design. A protocol was developed to collect and categorize the literature into a systematic evidence map for transgenerational inheritance by health effects, exposures, and evidence streams following the Office of Health Assessment and Translation (OHAT) approach for conducting literature-based health assessments. A PubMed search yielded 63,758 unique records from which 257 relevant studies were identified and categorized into a systematic evidence map by evidence streams (46 human and 211 animal), broad health effect categories, and exposures. Data extracted from the individual studies are available in the Health Assessment Workspace Collaborative (HAWC) program. There are relatively few bodies of evidence where multiple studies evaluated the same exposure and the same or similar outcomes. Studies evaluated for risk of bias generally had multiple issues in design or conduct. The evidence mapping illustrated that risk of bias, few studies, and heterogeneity in exposures and endpoints examined present serious limitations to available bodies of evidence for assessing transgenerational effects. Targeted research is suggested to addressed inconsistencies and risk of bias issues identified, and thereby establish more robust bodies of evidence to

Genetic variation of transgenerational plasticity of offspring germination in response to salinity stress and the seed transcriptome of Medicago truncatula.

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Vu, Wendy T; Chang, Peter L; Moriuchi, Ken S; Friesen, Maren L

2015-04-01

Transgenerational plasticity provides phenotypic variation that contributes to adaptation. For plants, the timing of seed germination is critical for offspring survival in stressful environments, as germination timing can alter the environmental conditions a seedling experiences. Stored seed transcripts are important determinants of seed germination, but have not previously been linked with transgenerational plasticity of germination behavior. In this study we used RNAseq and growth chamber experiments of the model legume M. trucantula to test whether parental exposure to salinity stress influences the expression of stored seed transcripts and early offspring traits and test for genetic variation. We detected genotype-dependent parental environmental effects (transgenerational plasticity) on the expression levels of stored seed transcripts, seed size, and germination behavior of four M. truncatula genotypes. More than 50% of the transcripts detected in the mature, ungerminated seed transcriptome were annotated as regulating seed germination, some of which are involved in abiotic stress response and post-embryonic development. Some genotypes showed increased seed size in response to parental exposure to salinity stress, but no parental environmental influence on germination timing. In contrast, other genotypes showed no seed size differences across contrasting parental conditions but displayed transgenerational plasticity for germimation timing, with significantly delayed germination in saline conditions when parental plants were exposed to salinity. In genotypes that show significant transgenerational plastic germination response, we found significant coexpression networks derived from salt responsive transcripts involved in post-transcriptional regulation of the germination pathway. Consistent with the delayed germination response to saline conditions in these genotypes, we found genes associated with dormancy and up-regulation of abscisic acid (ABA). Our results

Transgenerational Effects Alter Plant Defense and Resistance in Nature

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Colicchio, Jack

2017-01-01

Trichomes, or leaf hairs, are epidermal extensions that take a variety of forms and perform many functions in plants, including herbivore defense. In this study, I document genetically determined variation, within-generation plasticity, and a direct role of trichomes in herbivore defense for Mimulus guttatus. After establishing the relationship between trichomes and herbivory, I test for transgenerational effects of wounding on trichome density and herbivore resistance. Patterns of inter-annual variation in herbivore density and the high cost of plant defense makes plant-herbivore interactions a system in which transgenerational phenotypic plasticity (TPP) is apt to evolve. Here, I demonstrate that parental damage alters offspring trichome density and herbivore resistance in nature. Moreover, this response varies between populations. This is among the first studies to demonstrate that TPP contributes to variation in nature, and also suggests that selection can modify TPP in response to local conditions. PMID:28102915

Relationship between trans-generational effects of tetracycline on Daphnia magna at the physiological and whole organism level

International Nuclear Information System (INIS)

Kim, Hyun Young; Yu, Seungho; Jeong, Tae-yong; Kim, Sang Don

2014-01-01

The effects of pharmaceuticals have been underestimated during single generation exposure. Therefore, in this study, we investigated toxic responses at the physiological and whole organism level in tetracycline-exposed Daphnia magna over four consecutive generational lifecycles. The results showed that tetracycline affected energy-related physiological functions in concentration- and generation-dependent manners, and especially maintenance costs increased. Consequently, multigenerational exposure to tetracycline induced changes in energy balance, resulting in the change of higher levels of biological responses. In contrast, D. magna acclimated to tetracycline exposure over multiple generations, as evidenced by the increased LC 50 values. Transgenerational adaptation was related to the neonatal sensitivity and energy reserves of the organism. The results also emphasized the idea that the number of generation is an important factor for toxicity. The present study confirmed that toxic stress induces metabolic changes in an organism, thereby leading to increased energy consumption that results in adverse effects on reproduction. - Highlights: • Transgenerational adaptation of D. magna to tetracycline was observed. • TCN affected energy-related physiological function and increased maintenance energy. • LC 50 value of TCN increased with increasing concentration and generation. • The number of exposure generation may be an important factor for toxicity. - The change in internal energy balance in daphnids during multigenerational exposure to tetracycline may explain whole organism responses

Transgenerational plasticity as an important mechanism affecting response of clonal species to changing climate.

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Münzbergová, Zuzana; Hadincová, Věroslava

2017-07-01

In spite of the increasing number of studies on the importance of transgenerational plasticity for species response to novel environments, its effects on species ability to respond to climate change are still largely unexplored. We study the importance of transgenerational plasticity for response of a clonal species Festuca rubra . Individuals from four natural populations representing two levels of temperature and two levels of precipitation were cultivated in four growth chambers that simulate the temperature and precipitation of origin of the populations (maternal phase). Each population was represented in each growth chamber. After 6 months, single young ramets of these plants were reshuffled among the growth chambers and let to grow for additional 2 months (offspring phase). The results show that transgenerational effects (i.e., maternal phase conditions) significantly modify species response to novel climates, and the direction and intensity of the response depend on the climate of origin of the plants. For traits related to recourse acquisition, the conditions of maternal phase, either alone or in interaction mainly with climate of origin, had stronger effect than the conditions of cultivation. Overall, the maternal climate interacted more intensively with the climate of origin than with the offspring climate. The direction of the effect of the maternal climate was of different directions and intensities depending on plant origin and trait studied. The data demonstrated strong significant effects of conditions during maternal phase on species response to novel climates. These transgenerational affects were, however, not adaptive. Still, transgenerational plasticity may be an important driver of species response to novel conditions across clonal generations. These effects thus need to be carefully considered in future studies exploring species response to novel climates. This will also have strong effects on species performance under increasingly variable

Trans-generational responses to low pH depend on parental gender in a calcifying tubeworm

OpenAIRE

Lane, Ackley; Campanati, Camilla; Dupont, Sam; Thiyagarajan, Vengatesen

2015-01-01

The uptake of anthropogenic CO2 emissions by oceans has started decreasing pH and carbonate ion concentrations of seawater, a process called ocean acidification (OA). Occurring over centuries and many generations, evolutionary adaptation and epigenetic transfer will change species responses to OA over time. Trans-generational responses, via genetic selection or trans-generational phenotypic plasticity, differ depending on species and exposure time as well as differences between individuals su...

No evidence for thermal transgenerational plasticity in metabolism when minimizing the potential for confounding effects

OpenAIRE

Kielland, Øystein Nordeide; Bech, Claus; Einum, Sigurd

2017-01-01

Environmental change may cause phenotypic changes that are inherited across generations through transgenerational plasticity (TGP). If TGP is adaptive, offspring fitness increases with an increasing match between parent and offspring environment. Here we test for adaptive TGP in somatic growth and metabolic rate in response to temperature in the clonal zooplankton Daphnia pulex. Animals of the first focal generation experienced thermal transgenerational ‘mismatch’ (parental and offspring temp...

Transgenerational effects alter plant defence and resistance in nature.

Science.gov (United States)

Colicchio, J

2017-04-01

Trichomes, or leaf hairs, are epidermal extensions that take a variety of forms and perform many functions in plants, including herbivore defence. In this study, I document genetically determined variation, within-generation plasticity, and a direct role of trichomes in herbivore defence for Mimulus guttatus. After establishing the relationship between trichomes and herbivory, I test for transgenerational effects of wounding on trichome density and herbivore resistance. Patterns of interannual variation in herbivore density and the high cost of plant defence makes plant-herbivore interactions a system in which transgenerational phenotypic plasticity (TPP) is apt to evolve. Here, I demonstrate that parental damage alters offspring trichome density and herbivore resistance in nature. Moreover, this response varies between populations. This is among the first studies to demonstrate that TPP contributes to variation in nature, and also suggests that selection can modify TPP in response to local conditions. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Trans-generational plasticity in response to immune challenge is constrained by heat stress.

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Roth, Olivia; Landis, Susanne H

2017-06-01

Trans-generational plasticity (TGP) is the adjustment of phenotypes to changing habitat conditions that persist longer than the individual lifetime. Fitness benefits (adaptive TGP) are expected upon matching parent-offspring environments. In a global change scenario, several performance-related environmental factors are changing simultaneously. This lowers the predictability of offspring environmental conditions, potentially hampering the benefits of TGP. For the first time, we here explore how the combination of an abiotic and a biotic environmental factor in the parental generation plays out as trans-generational effect in the offspring. We fully reciprocally exposed the parental generation of the pipefish Syngnathus typhle to an immune challenge and elevated temperatures simulating a naturally occurring heatwave. Upon mating and male pregnancy, offspring were kept in ambient or elevated temperature regimes combined with a heat-killed bacterial epitope treatment. Differential gene expression (immune genes and DNA- and histone-modification genes) suggests that the combined change of an abiotic and a biotic factor in the parental generation had interactive effects on offspring performance, the temperature effect dominated over the immune challenge impact. The benefits of certain parental environmental conditions on offspring performance did not sum up when abiotic and biotic factors were changed simultaneously supporting that available resources that can be allocated to phenotypic trans-generational effects are limited. Temperature is the master regulator of trans-generational phenotypic plasticity, which potentially implies a conflict in the allocation of resources towards several environmental factors. This asks for a reassessment of TGP as a short-term option to buffer environmental variation in the light of climate change.

Adaptive Transgenerational Plasticity in Plants: Case Studies, Mechanisms, and Implications for Natural Populations

OpenAIRE

Herman, Jacob J.; Sultan, Sonia E.

2011-01-01

Plants respond to environmental conditions not only by plastic changes to their own development and physiology, but also by altering the phenotypes expressed by their offspring. This transgenerational plasticity was initially considered to entail only negative effects of stressful parental environments, such as production of smaller seeds by resource- or temperature-stressed parent plants, and was therefore viewed as environmental noise. Recent evolutionary ecology studies have shown that in ...

Species-specific and transgenerational responses to increasing salinity in sympatric freshwater gastropods

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Suski, Jamie G.; Salice, Christopher J.; Patino, Reynaldo

2012-01-01

Freshwater salinization is a global concern partly attributable to anthropogenic salt contamination. The authors examined the effects of increased salinity (as NaCl, 250-4,000 µS/cm, specific conductance) on two sympatric freshwater gastropods (Helisoma trivolvis and Physa pomillia). Life stage sensitivities were determined by exposing naive eggs or naive juveniles (through adulthood and reproduction). Additionally, progeny eggs from the juvenile-adult exposures were maintained at their respective parental salinities to examine transgenerational effects. Naive H. trivolvis eggs experienced delayed development at specific conductance > 250 µS/cm; reduced survivorship and reproduction were also seen in juvenile H. trivolvis at 4,000 µS/cm. Survival and growth of P. pomilia were not affected by increased salinity following egg or juvenile exposures. Interestingly, the progeny of H. trivolvis exposed to higher salinity may have gained tolerance to increased salinity whereas P. pomilia progeny may have experienced negative transgenerational effects. The present study demonstrates that freshwater snail species vary in their tolerance to salinization and also highlights the importance of multigenerational studies, as stressor impacts may not be readily apparent from shorter term exposures.

Transgenerational developmental programming.

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Aiken, Catherine E; Ozanne, Susan E

2014-01-01

The concept of developmental programming suggests that the early life environment influences offspring characteristics in later life, including the propensity to develop diseases such as the metabolic syndrome. There is now growing evidence that the effects of developmental programming may also manifest in further generations without further suboptimal exposure. This review considers the evidence, primarily from rodent models, for effects persisting to subsequent generations, and evaluates the mechanisms by which developmental programming may be transmitted to further generations. In particular, we focus on the potential role of the intrauterine environment in contributing to a developmentally programmed phenotype in subsequent generations. The literature was systematically searched at http://pubmed.org and http://scholar.google.com to identify published findings regarding transgenerational (F2 and beyond) developmental programming effects in human populations and animal models. Transmission of programming effects is often viewed as a form of epigenetic inheritance, either via the maternal or paternal line. Evidence exists for both germline and somatic inheritance of epigenetic modifications which may be responsible for phenotypic changes in further generations. However, there is increasing evidence for the role of both extra-genomic components of the zygote and the interaction of the developing conceptus with the intrauterine environment in propagating programming effects. The contribution of a suboptimal reproductive tract environment or maternal adaptations to pregnancy may be critical to inheritance of programming effects via the maternal line. As the effects of age exacerbate the programmed metabolic phenotype, advancing maternal age may increase the likelihood of developmental programming effects being transmitted to further generations. We suggest that developmental programming effects could be propagated through the maternal line de novo in generations

Transgenerational plasticity is sex-dependent and persistent in yellow monkeyflower (Mimulus guttatus).

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Akkerman, Kayla C; Sattarin, Arash; Kelly, John K; Scoville, Alison G

2016-04-01

Transgenerational phenotypic plasticity, whereby environmental cues experienced by parents alter the phenotype of their progeny, has now been documented in diverse organisms. Transmission of environmentally determined responses is known to occur through both maternal and paternal gametes, but the underlying mechanisms have rarely been compared. In addition, the persistence of induction over multiple generations appears to vary widely, but has been characterized for relatively few systems. Yellow monkeyflower ( Mimulus guttatus ) is known to exhibit transgenerational induction of increased glandular trichome production in response to simulated insect damage. Here, we test for differences between maternal and paternal transmission of this response and examine its persistence over five generations following damage. Maternal and paternal damage resulted in similar and apparently additive increases in progeny trichome production. Treatment of germinating seeds with the genome-wide demethylating agent 5-azacytidine erased the effect of maternal but not paternal damage. The number of glandular trichomes remained elevated for three generations following damage. These results indicate that transgenerational transmission occurs through both maternal and paternal germ lines, but that they differ in the proximate mechanism of epigenetic inheritance. Our results also indicate that a wounding response can persist for multiple generations in the absence of subsequent damage.

DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

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Marchetti, Francesco; Wyrobek, Andrew J.

2009-01-18

Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization. During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.

Transgenerational effect of neighborhood poverty on low birth weight among African Americans in Cook County, Illinois.

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Collins, James W; David, Richard J; Rankin, Kristin M; Desireddi, Jennifer R

2009-03-15

In perinatal epidemiology, transgenerational risk factors are defined as conditions experienced by one generation that affect the pregnancy outcomes of the next generation. The authors investigated the transgenerational effect of neighborhood poverty on infant birth weight among African Americans. Stratified and multilevel logistic regression analyses were performed on an Illinois transgenerational data set with appended US Census income information. Singleton African-American infants (n = 40,648) born in 1989-1991 were considered index births. The mothers of index infants had been born in 1956-1976. The maternal grandmothers of index infants were identified. Rates of infant low birth weight (birth weight for maternal grandmother's residence in a poor neighborhood (compared with an affluent neighborhood) equaled 1.3 (95% confidence interval: 1.1, 1.4). This study suggests that maternal grandmother's exposure to neighborhood poverty during her pregnancy is a risk factor for infant low birth weight among African Americans.

A review on the evidence of transgenerational transmission of posttraumatic stress disorder vulnerability

Directory of Open Access Journals (Sweden)

Seyyed Taha Yahyavi

2014-03-01

Full Text Available Objective: To understand the risks of posttraumatic stress disorder (PTSD development in the next generation of PTSD patients, we conducted a review on the biological, but not genetic, evidence of transgenerational transmission of PTSD vulnerability. Methods: Pertinent articles published from 1985 to September 2011 were searched using online academic search engines, including MEDLINE, EMBASE, ScienceDirect, OVID, PsycLIT, and SCOPUS, and a non-systematic review was conducted. Results: There is paradoxical evidence that hypothalamic-pituitary-adrenal axis changes in PTSD patients may also be evident in their offspring. This effect and biological vulnerability to PTSD may be transmitted across generations through maternal epigenetic programming during pregnancy. The samples of most studies, which were not large enough and represented the outcome of few research groups, consisted of a specific type of patients with a particular trauma. Conclusions: There is still a need to conduct studies in other geographical areas with different genetic background and larger samples considering different types of trauma other than those specified in the current literature, so as to strengthen the evidence of transgenerational transmission of PTSD vulnerability.

Thoughts on the cultural evolution of man. Developmental imprinting and transgenerational effect.

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Csaba, György

2007-01-01

The biological evolution of man stopped since it has been conveyed to the objects, created by man. This paper introduces the concept of "conveyed evolution". Being part of the cultural evolution, the conveyed evolution is a continuation of the biological one. There are several similarities between the laws of biological and conveyed evolution, albeit the differences are important as well. Some laws of the conveyed evolution are described here. The conveyed evolution has man-made repair mechanisms (medicine, protection of environment) which defend man from harm. Man's fragility limits the progress of conveyed evolution. However, artificial compounds or environmental pollutants which are provoked by the conveyed evolution induce chemical (hormonal) imprinting in the developmental critical periods, which is transmitted to the progeny generations (transgenerational effect). This could cause evolutionary alterations without mutation.

Sodium provides unique insights into transgenerational effects of ocean acidification on bivalve shell formation.

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Zhao, Liqiang; Schöne, Bernd R; Mertz-Kraus, Regina; Yang, Feng

2017-01-15

Ocean acidification is likely to have profound impacts on marine bivalves, especially on their early life stages. Therefore, it is imperative to know whether and to what extent bivalves will be able to acclimate or adapt to an acidifying ocean over multiple generations. Here, we show that reduced seawater pH projected for the end of this century (i.e., pH7.7) led to a significant decrease of shell production of newly settled juvenile Manila clams, Ruditapes philippinarum. However, juveniles from parents exposed to low pH grew significantly faster than those from parents grown at ambient pH, exhibiting a rapid transgenerational acclimation to an acidic environment. The sodium composition of the shells may shed new light on the mechanisms responsible for beneficial transgenerational acclimation. Irrespective of parental exposure, the amount of Na incorporated into shells increased with decreasing pH, implying active removal of excessive protons through the Na + /H + exchanger which is known to depend on the Na + gradient actively built up by the Na + /K + -ATPase as a driving force. However, the shells with a prior history of transgenerational exposure to low pH recorded significantly lower amounts of Na than those with no history of acidic exposure. It therefore seems very likely that the clams may implement less costly and more ATP-efficient ion regulatory mechanisms to maintain pH homeostasis in the calcifying fluid following transgenerational acclimation. Our results suggest that marine bivalves may have a greater capacity to acclimate or adapt to ocean acidification by the end of this century than currently understood. Copyright © 2016 Elsevier B.V. All rights reserved.

Non-genomic transgenerational inheritance of disease risk.

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Gluckman, Peter D; Hanson, Mark A; Beedle, Alan S

2007-02-01

That there is a heritable or familial component of susceptibility to chronic non-communicable diseases such as type 2 diabetes, obesity and cardiovascular disease is well established, but there is increasing evidence that some elements of such heritability are transmitted non-genomically and that the processes whereby environmental influences act during early development to shape disease risk in later life can have effects beyond a single generation. Such heritability may operate through epigenetic mechanisms involving regulation of either imprinted or non-imprinted genes but also through broader mechanisms related to parental physiology or behaviour. We review evidence and potential mechanisms for non-genomic transgenerational inheritance of 'lifestyle' disease and propose that the 'developmental origins of disease' phenomenon is a maladaptive consequence of an ancestral mechanism of developmental plasticity that may have had adaptive value in the evolution of generalist species such as Homo sapiens. Copyright 2007 Wiley Periodicals, Inc.

The effects of in utero irradiation on mutation induction and transgenerational instability in mice

International Nuclear Information System (INIS)

Barber, Ruth C.; Hardwick, Robert J.; Shanks, Morag E.; Glen, Colin D.; Mughal, Safeer K.; Voutounou, Mariel; Dubrova, Yuri E.

2009-01-01

Epidemiological evidence suggests that the deleterious effects of prenatal irradiation can manifest during childhood, resulting in an increased risk of leukaemia and solid cancers after birth. However, the mechanisms underlying the long-term effects of foetal irradiation remain poorly understood. This study was designed to analyse the impact of in utero irradiation on mutation rates at expanded simple tandem repeat (ESTR) DNA loci in directly exposed mice and their first-generation (F 1 ) offspring. ESTR mutation frequencies in the germline and somatic tissues of male and female mice irradiated at 12 days of gestation remained highly elevated during adulthood, which was mainly attributed to a significant increase in the frequency of singleton mutations. The prevalence of singleton mutations in directly exposed mice suggests that foetal irradiation results in genomic instability manifested both in utero and during adulthood. The frequency of ESTR mutation in the F 1 offspring of prenatally irradiated male mice was equally elevated across all tissues, which suggests that foetal exposure results in transgenerational genomic instability. In contrast, maternal in utero exposure did not affect the F 1 stability. Our data imply that the passive erasure of epigenetic marks in the maternal genome can diminish the transgenerational effects of foetal irradiation and therefore provide important clues to the still unknown mechanisms of radiation-induced genomic instability. The results of this study offer a plausible explanation for the effects of in utero irradiation on the risk of leukaemia and solid cancers after birth.

Thermal legacies: transgenerational effects of temperature on growth in a vertebrate.

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Salinas, Santiago; Munch, Stephan B

2012-02-01

Transgenerational plasticity (TGP), a generalisation of more widely studied maternal effects, occurs whenever environmental cues experienced by either parent prior to fertilisation results in a modification of offspring reaction norms. Such effects have been observed in many traits across many species. Despite enormous potential importance-particularly in an era of rapid climate change-TGP in thermal growth physiology has never been demonstrated for vertebrates. We provide the first evidence for thermal TGP in a vertebrate: given sufficient time, sheepshead minnows adaptively program their offspring for maximal growth at the present temperature. The change in growth over a single generation (c. 30%) exceeds the single-generation rate of adaptive evolution by an order of magnitude. If widespread, transgenerational effects on thermal performance may have important implications on physiology, ecology and contemporary evolution, and may significantly alter the extinction risk posed by changing climate. © 2011 Blackwell Publishing Ltd/CNRS.

The Effects of Trauma, with or without PTSD, on the Transgenerational DNA Methylation Alterations in Human Offsprings.

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Youssef, Nagy A; Lockwood, Laura; Su, Shaoyong; Hao, Guang; Rutten, Bart P F

2018-05-08

Exposure to psychological trauma is a strong risk factor for several debilitating disorders including post-traumatic stress disorder (PTSD) and depression. Besides the impact on mental well-being and behavior in the exposed individuals, it has been suggested that psychological trauma can affect the biology of the individuals, and even have biological and behavioral consequences on the offspring of exposed individuals. While knowledge of possible epigenetic underpinnings of the association between exposure to trauma and risk of PTSD has been discussed in several reviews, it remains to be established whether trauma-induced epigenetic modifications can be passed from traumatized individuals to subsequent generations of offspring. The aim of this paper is to review the emerging literature on evidence of transgenerational inheritance due to trauma exposure on the epigenetic mechanism of DNA methylation in humans. Our review found an accumulating amount of evidence of an enduring effect of trauma exposure to be passed to offspring transgenerationally via the epigenetic inheritance mechanism of DNA methylation alterations and has the capacity to change the expression of genes and the metabolome. This manuscript summarizes and critically reviews the relevant original human studies in this area. Thus, it provides an overview of where we stand, and a clearer vision of where we should go in terms of future research directions.

Transgenerational Social Stress Alters Immune–Behavior Associations and the Response to Vaccination

Directory of Open Access Journals (Sweden)

Alexandria Hicks-Nelson

2017-07-01

Full Text Available Similar to the multi-hit theory of schizophrenia, social behavior pathologies are mediated by multiple factors across generations, likely acting additively, synergistically, or antagonistically. Exposure to social adversity, especially during early life, has been proposed to induce depression symptoms through immune mediated mechanisms. Basal immune factors are altered in a variety of neurobehavioral models. In the current study, we assessed two aspects of a transgenerational chronic social stress (CSS rat model and its effects on the immune system. First, we asked whether exposure of F0 dams and their F1 litters to CSS changes basal levels of IL-6, TNF, IFN-γ, and social behavior in CSS F1 female juvenile rats. Second, we asked whether the F2 generation could generate normal immunological responses following vaccination with Mycobacterium bovis Bacillus Calmette–Guérin (BCG. We report several changes in the associations between social behaviors and cytokines in the F1 juvenile offspring of the CSS model. It is suggested that changes in the immune–behavior relationships in F1 juveniles indicate the early stages of immune mediated disruption of social behavior that becomes more apparent in F1 dams and the F2 generation. We also report preliminary evidence of elevated IL-6 and impaired interferon-gamma responses in BCG-vaccinated F2 females. In conclusion, transgenerational social stress alters both immune–behavior associations and responses to vaccination. It is hypothesized that the effects of social stress may accumulate over generations through changes in the immune system, establishing the immune system as an effective preventative or treatment target for social behavior pathologies.

Within- and trans-generational plasticity affects the opportunity for selection in barbed goatgrass (Aegilops triuncialis).

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Espeland, Erin K; Rice, Kevin J

2012-12-01

Environments are composed of selective agents, and environments may also modify the efficacy of these agents. Environments affect the rate of maximum evolutionary change by influencing variation in relative fitness (i.e., the opportunity for selection, or I). Within- and transgenerational plastic environmental responses may affect I, speeding or slowing processes of local adaptation. • We determined whether environmental factors affected the opportunity for selection (I) in Aegilops triuncialis (barbed goatgrass) by measuring I as a within- and transgenerational plastic response to two maternal glasshouse environments (serpentine/dry and loam/moist). We also determined whether this species' two most common genetic lineages (determined by DNA microsatellite length polymorphism) varied in response to glasshouse treatments. • Opportunity for selection was less for plants grown in the dry serpentine environment than for plants grown in the moist loam environment. This response varied between genetic lineages. The east lineage exhibited a within-generation response to the dry serpentine environment. For both seed mass and average seed weight in this lineage, the opportunity for selection was lower in dry serpentine than in moist loam. The west lineage had a transgenerational response to the dry serpentine such that the opportunity for selection for seed number and seed mass was lower for plants produced by mothers grown in dry serpentine than for plants produced by mothers in moist loam. • Phenotypic variation in relative fitness is constrained by the dry serpentine environment, which leads to lower evolvability in this environment. Within- and transgenerational effects of the environment may slow local adaptation to serpentine soils.

Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis.

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Anway, Matthew D; Memon, Mushtaq A; Uzumcu, Mehmet; Skinner, Michael K

2006-01-01

The current study was designed to examine the actions of a model endocrine disruptor on embryonic testis development and male fertility. Pregnant rats (F0) that received a transient embryonic exposure to an environmental endocrine disruptor, vinclozolin, had male offspring (F1) with reduced spermatogenic capacity. The reduced spermatogenetic capacity observed in the F1 male offspring was transmitted to the subsequent generations (F2-F4). The administration of vinclozolin, an androgen receptor antagonist, at 100 mg/kg/day from embryonic day 8-14 (E8-E14) of pregnancy to only the F0 dam resulted in a transgenerational phenotype in the subsequent male offspring in the F1-F4 generations. The litter size and male/female sex ratios were similar in controls and the vinclozolin generations. The average testes/body weight index of the postnatal day 60 (P60) males was not significantly different in the vinclozolin-treated generations compared to the controls. However, the testicular spermatid number, as well as the epididymal sperm number and motility, were significantly reduced in the vinclozolin generations compared to the control animals. Postnatal day 20 (P20) testis from the vinclozolin F2 generation had no morphological abnormalities, but did have an increase in spermatogenic cell apoptosis. Although the P60 testis morphology was predominantly normal, the germ cell apoptosis was significantly increased in the testes cross sections of animals from the vinclozolin generations. The increase in apoptosis was stage-specific in the testis, with tubules at stages IX-XIV having the highest increase in apoptotic germ cells. The tubules at stages I-V also had an increase in apoptotic germ cells compared to the control samples, but tubules at stages VI-VIII had no increase in apoptotic germ cells. An outcross of a vinclozolin generation male with a wild-type female demonstrated that the reduced spermatogenic cell phenotype was transmitted through the male germ line. An outcross

Transgenerational effects alleviate severe fecundity loss during ocean acidification in a ubiquitous planktonic copepod.

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Thor, Peter; Dupont, Sam

2015-06-01

Ocean acidification (OA) caused by anthropogenic CO2 emission is projected for thousands of years to come, and significant effects are predicted for many marine organisms. While significant evolutionary responses are expected during such persistent environmental change, most studies consider only short-term effects. Little is known about the transgenerational effects of parental environments or natural selection on the capacity of populations to counter detrimental OA effects. In this study, six laboratory populations of the calanoid copepod Pseudocalanus acuspes were established at three different CO2 partial pressures (pCO2 of 400, 900 and 1550 μatm) and grown for two generations at these conditions. Our results show evidence of alleviation of OA effects as a result of transgenerational effects in P. acuspes. Second generation adults showed a 29% decrease in fecundity at 900 μatm CO2 compared to 400 μatm CO2 . This was accompanied by a 10% increase in metabolic rate indicative of metabolic stress. Reciprocal transplant tests demonstrated that this effect was reversible and the expression of phenotypic plasticity. Furthermore, these tests showed that at a pCO2 exceeding the natural range experienced by P. acuspes (1550 μatm), fecundity would have decreased by as much as 67% compared to at 400 μatm CO2 as a result of this plasticity. However, transgenerational effects partly reduced OA effects so that the loss of fecundity remained at a level comparable to that at 900 μatm CO2 . This also relieved the copepods from metabolic stress, and respiration rates were lower than at 900 μatm CO2 . These results highlight the importance of tests for transgenerational effects to avoid overestimation of the effects of OA. © 2014 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

Transgenerational isotopic marking of carp Cyprinus carpio, L. using a 86Sr /84Sr double spike

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Zitek, Andreas; Cervicek, Magdalena; Irrgeher, Johanna; Horsky, Monika; Kletzl, Manfred; Weismann, Thomas; Prohaska, Thomas

2013-04-01

Transgenerational isotopic marking has been recognized recently as an effective tool for mass marking and tracking of individual fish to their original source. Compared to other conventional marking techniques, transgenerational marking offers several advantages. Most importantly, it is possible to mark all offspring of one individual female without the necessity of handling eggs or larval fish. Furthermore it is possible to vary the concentrations of individual isotopes to obtain specific marks for individual female fish. An enriched isotopic spike solution is usually applied to gravid female spawners by injection into the body cavity for transgenerational marking. The isotope is then incorporated into the central otolith region of the offspring which is known to be built up by maternally derived material. Within this study transgenerational marking of a typical cyprinid fish species, Cyprinus carpio, L., was tested using a 86Sr /84Sr double spike. Buffered solutions with different isotopic composition and concentrations were administered to 4 female individuals by intraperitoneal injection 5 days before spawning, while one female was injected a blank solution. After spawning, otoliths (Lapilli) from juvenile fish were sampled at the age of about 5 months at fish sizes between 3 and 4 cm and analyzed for their isotopic composition by LA-ICPMS applying cross sectional line scans. Central otolith regions of the progeny showed a shift in the natural isotope ratios for the administered isotopes. Deconvolution of the blank corrected measurement data of the Sr isotopes was done to trace back the original spike ratio. The different spike ratios could be well distinguished reflecting the original composition of the spike solution. This study proved that it is possible to create batch-specific unique transgenerational marks in otolith cores by varying the concentrations of two naturally occurring Sr isotopes. This method has high potential to reduce the marking effort for

Transgenerational transmission of a stress-coping phenotype programmed by early-life stress in the Japanese quail

Science.gov (United States)

Zimmer, Cédric; Larriva, Maria; Boogert, Neeltje J.; Spencer, Karen A.

2017-01-01

An interesting aspect of developmental programming is the existence of transgenerational effects that influence offspring characteristics and performance later in life. These transgenerational effects have been hypothesized to allow individuals to cope better with predictable environmental fluctuations and thus facilitate adaptation to changing environments. Here, we test for the first time how early-life stress drives developmental programming and transgenerational effects of maternal exposure to early-life stress on several phenotypic traits in their offspring in a functionally relevant context using a fully factorial design. We manipulated pre- and/or post-natal stress in both Japanese quail mothers and offspring and examined the consequences for several stress-related traits in the offspring generation. We show that pre-natal stress experienced by the mother did not simply affect offspring phenotype but resulted in the inheritance of the same stress-coping traits in the offspring across all phenotypic levels that we investigated, shaping neuroendocrine, physiological and behavioural traits. This may serve mothers to better prepare their offspring to cope with later environments where the same stressors are experienced. PMID:28387355

The role of adaptive trans-generational plasticity in biological invasions of plants

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Trans-generational plasticity (TGP) that confers greater offspring fitness is likely to be an important mechanism contributing to the spread of some invasive plant species. TGP is predicted for populations found in habitats with predictable spatial or temporal resource heterogeneity, and that have ...

Transgenerational interactions between a pesticide and warming in a vector mosquito

DEFF Research Database (Denmark)

Tran, T.; Dinh, Khuong Van; Stoks, R.

may change in a polluted environment. We set up a full-factorial transgenerational experiment where Culex pipiens vector mosquitoes were reared at two temperatures (20°C vs 24°C) and, when they reached the final larval stage, exposed to one of two chlorpyrifos treatments (absent vs present). We...

Molecular characterization of a rice mutator-phenotype derived from an incompatible cross-pollination reveals transgenerational mobilization of multiple transposable elements and extensive epigenetic instability

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Xu Chunming

2009-05-01

Full Text Available Abstract Background Inter-specific hybridization occurs frequently in plants, which may induce genetic and epigenetic instabilities in the resultant hybrids, allopolyploids and introgressants. It remains unclear however whether pollination by alien pollens of an incompatible species may impose a "biological stress" even in the absence of genome-merger or genetic introgression, whereby genetic and/or epigenetic instability of the maternal recipient genome might be provoked. Results We report here the identification of a rice mutator-phenotype from a set of rice plants derived from a crossing experiment involving two remote and apparently incompatible species, Oryza sativa L. and Oenothera biennis L. The mutator-phenotype (named Tong211-LP showed distinct alteration in several traits, with the most striking being substantially enlarged panicles. Expectably, gel-blotting by total genomic DNA of the pollen-donor showed no evidence for introgression. Characterization of Tong211-LP (S0 and its selfed progenies (S1 ruled out contamination (via seed or pollen or polyploidy as a cause for its dramatic phenotypic changes, but revealed transgenerational mobilization of several previously characterized transposable elements (TEs, including a MITE (mPing, and three LTR retrotransposons (Osr7, Osr23 and Tos17. AFLP and MSAP fingerprinting revealed extensive, transgenerational alterations in cytosine methylation and to a less extent also genetic variation in Tong211-LP and its immediate progenies. mPing mobility was found to correlate with cytosine methylation alteration detected by MSAP but not with genetic variation detected by AFLP. Assay by q-RT-PCR of the steady-state transcript abundance of a set of genes encoding for the various putative DNA methyltransferases, 5-methylcytosine DNA glycosylases, and small interference RNA (siRNA pathway-related proteins showed that, relative to the rice parental line, heritable perturbation in expression of 12 out of

Activity strengths of cortical glutamatergic and GABAergic neurons are correlated with transgenerational inheritance of learning ability.

Science.gov (United States)

Liu, Yulong; Ge, Rongjing; Zhao, Xin; Guo, Rui; Huang, Li; Zhao, Shidi; Guan, Sudong; Lu, Wei; Cui, Shan; Wang, Shirlene; Wang, Jin-Hui

2017-12-22

The capabilities of learning and memory in parents are presumably transmitted to their offsprings, in which genetic codes and epigenetic regulations are thought as molecular bases. As neural plasticity occurs during memory formation as cellular mechanism, we aim to examine the correlation of activity strengths at cortical glutamatergic and GABAergic neurons to the transgenerational inheritance of learning ability. In a mouse model of associative learning, paired whisker and odor stimulations led to odorant-induced whisker motion, whose onset appeared fast (high learning efficiency, HLE) or slow (low learning efficiency, LLE). HLE male and female mice, HLE female and LLE male mice as well as HLE male and LLE female mice were cross-mated to have their first generation of offsprings, filials (F1). The onset of odorant-induced whisker motion appeared a sequence of high-to-low efficiency in three groups of F1 mice that were from HLE male and female mice, HLE female and LLE male mice as well as HLE male and LLE female mice. Activities related to glutamatergic neurons in barrel cortices appeared a sequence of high-to-low strength in these F1 mice from HLE male and female mice, HLE female and LLE male mice as well as HLE male and LLE female mice. Activities related to GABAergic neurons in barrel cortices appeared a sequence of low-to-high strength in these F1 mice from HLE male and female mice, HLE female and LLE male mice as well as HLE male and LLE female mice. Neuronal activity strength was linearly correlated to learning efficiency among three groups. Thus, the coordinated activities at glutamatergic and GABAergic neurons may constitute the cellular basis for the transgenerational inheritance of learning ability.

The Effects of Trauma, with or without PTSD, on the Transgenerational DNA Methylation Alterations in Human Offsprings

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Nagy A. Youssef

2018-05-01

Full Text Available Exposure to psychological trauma is a strong risk factor for several debilitating disorders including post-traumatic stress disorder (PTSD and depression. Besides the impact on mental well-being and behavior in the exposed individuals, it has been suggested that psychological trauma can affect the biology of the individuals, and even have biological and behavioral consequences on the offspring of exposed individuals. While knowledge of possible epigenetic underpinnings of the association between exposure to trauma and risk of PTSD has been discussed in several reviews, it remains to be established whether trauma-induced epigenetic modifications can be passed from traumatized individuals to subsequent generations of offspring. The aim of this paper is to review the emerging literature on evidence of transgenerational inheritance due to trauma exposure on the epigenetic mechanism of DNA methylation in humans. Our review found an accumulating amount of evidence of an enduring effect of trauma exposure to be passed to offspring transgenerationally via the epigenetic inheritance mechanism of DNA methylation alterations and has the capacity to change the expression of genes and the metabolome. This manuscript summarizes and critically reviews the relevant original human studies in this area. Thus, it provides an overview of where we stand, and a clearer vision of where we should go in terms of future research directions.

Transgenerational metamorphosis in Shakespeare’s Winter’s tale and the eurozone crisis

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Gerald Wooster

2014-09-01

Full Text Available Shakespeare’s The Winter’s Tale – set in Palermo, and also Bohemia - suggests that where there is close affection and love there also may be more exposure to envy, jealousy, uncontrolled anger,attempts to punish, and guilt. It involves inter-sibling and inter-group dynamics, attributions, misattributions, but also transgenerational metapmorphosis creating new meanings, and how envy and jealousy - if reconciled – may redeem guilt and generate psychic surpluses rather than only deficits. The paper outlines these but also relates such dynamics to the current crisis of the Eurozone and Kleinian splitting and projective identification. It suggests that the crisis is the first time Germany that Germany has been able to split from guilt (Schuld – especially for the Holocaust – and been able to project guilt for debt (also Schuld in German onto the peripheral European countries, and that transgenerational metapmorphosis will depend on recovering the good in credit as the inverse of debt. Key words: Jealousy, Guilt, Debt.

Transgenerational metamorphosis in Shakespeare’s Winter’s tale and the eurozone crisis

Directory of Open Access Journals (Sweden)

Gerald Wooster

2014-09-01

Full Text Available Shakespeare’s The Winter’s Tale – set in Palermo, and also Bohemia - suggests that where there is close affection and love there also may be more exposure to envy, jealousy, uncontrolled anger,attempts to punish, and guilt. It involves inter-sibling and inter-group dynamics, attributions, misattributions, but also transgenerational metapmorphosis creating new meanings, and how envy and jealousy - if reconciled – may redeem guilt and generate psychic surpluses rather than only deficits. The paper outlines these but also relates such dynamics to the current crisis of the Eurozone and Kleinian splitting and projective identification. It suggests that the crisis is the first time Germany that Germany has been able to split from guilt (Schuld – especially for the Holocaust – and been able to project guilt for debt (also Schuld in German onto the peripheral European countries, and that transgenerational metapmorphosis will depend on recovering the good in credit as the inverse of debt. Keywords: Jealousy; Guilt; Debt 

Microbiome assembly of avian eggshells and their potential as transgenerational carriers of maternal microbiota.

Science.gov (United States)

van Veelen, H Pieter J; Salles, Joana Falcão; Tieleman, B Irene

2018-05-01

The microbiome is essential for development, health and homeostasis throughout an animal's life. Yet, the origins and transmission processes governing animal microbiomes remain elusive for non-human vertebrates, oviparous vertebrates in particular. Eggs may function as transgenerational carriers of the maternal microbiome, warranting characterisation of egg microbiome assembly. Here, we investigated maternal and environmental contributions to avian eggshell microbiota in wild passerine birds: woodlark Lullula arborea and skylark Alauda arvensis. Using 16S rRNA gene sequencing, we demonstrated in both lark species, at the population and within-nest levels, that bacterial communities of freshly laid eggs were distinct from the female cloacal microbiome. Instead, soil-borne bacteria appeared to thrive on freshly laid eggs, and eggshell microbiota composition strongly resembled maternal skin, body feather and nest material communities, sources in direct contact with laid eggs. Finally, phylogenetic structure analysis and microbial source tracking underscored species sorting from directly contacting sources rather than in vivo-transferred symbionts. The female-egg-nest system allowed an integrative assessment of avian egg microbiome assembly, revealing mixed modes of symbiont acquisition not previously documented for vertebrate eggs. Our findings illuminated egg microbiome origins, which suggested a limited potential of eggshells for transgenerational transmission, encouraging further investigation of eggshell microbiome functions in vertebrates.

Transgenerational acclimation of fishes to climate change and ocean acidification

OpenAIRE

Munday, Philip L.

2014-01-01

There is growing concern about the impacts of climate change and ocean acidification on marine organisms and ecosystems, yet the potential for acclimation and adaptation to these threats is poorly understood. Whereas many short-term experiments report negative biological effects of ocean warming and acidification, new studies show that some marine species have the capacity to acclimate to warmer and more acidic environments across generations. Consequently, transgenerational plasticity may be...

Irradiation of rainbow trout at early life stages results in trans-generational effects including the induction of a bystander effect in non-irradiated fish

International Nuclear Information System (INIS)

Smith, Richard W.; Seymour, Colin B.; Moccia, Richard D.; Mothersill, Carmel E.

2016-01-01

The bystander effect, a non-targeted effect (NTE) of radiation, which describes the response by non-irradiated organisms to signals emitted by irradiated organisms, has been documented in a number of fish species. However transgenerational effects of radiation (including NTE) have yet to be studied in fish. Therefore rainbow trout, which were irradiated as eggs at 48 h after fertilisation, eyed eggs, yolk sac larvae or first feeders, were bred to generate a F1 generation and these F1 fish were bred to generate a F2 generation. F1 and F2 fish were swam with non-irradiated bystander fish. Media from explants of F1 eyed eggs, F1 one year old fish gill and F1 two year old fish gill and spleen samples, and F2 two year old gill and spleen samples, as well as from bystander eggs/fish, was used to treat a reporter cell line, which was then assayed for changes in cellular survival/growth. The results were complex and dependent on irradiation history, age (in the case of the F1 generation), and were tissue specific. For example, irradiation of one parent often resulted in effects not seen with irradiation of both parents. This suggests that, unlike mammals, in certain circumstances maternal and paternal irradiation may be equally important. This study also showed that trout can induce a bystander effect 2 generations after irradiation, which further emphasises the importance of the bystander effect in aquatic radiobiology. Given the complex community structure in aquatic ecosystems, these results may have significant implications for environmental radiological protection. - Highlights: • We evaluated the transgenerational effect of early life irradiation in rainbow trout. • Trout irradiated as eggs, yolk sac larvae or first feeders were crossed. • A transgenerational effect was evident in two generations after irradiation. • F1 and F2 generation fish induced a bystander effect in non-irradiated fish. • The precise effects were tissue specific and dependent on

Irradiation of rainbow trout at early life stages results in trans-generational effects including the induction of a bystander effect in non-irradiated fish

Energy Technology Data Exchange (ETDEWEB)

Smith, Richard W., E-mail: rich.wilson.smith@gmail.com [Department of Animal Biosciences, University of Guelph, Guelph, Ontario (Canada); Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario (Canada); Seymour, Colin B. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario (Canada); Moccia, Richard D. [Department of Animal Biosciences, University of Guelph, Guelph, Ontario (Canada); Mothersill, Carmel E. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario (Canada)

2016-02-15

The bystander effect, a non-targeted effect (NTE) of radiation, which describes the response by non-irradiated organisms to signals emitted by irradiated organisms, has been documented in a number of fish species. However transgenerational effects of radiation (including NTE) have yet to be studied in fish. Therefore rainbow trout, which were irradiated as eggs at 48 h after fertilisation, eyed eggs, yolk sac larvae or first feeders, were bred to generate a F1 generation and these F1 fish were bred to generate a F2 generation. F1 and F2 fish were swam with non-irradiated bystander fish. Media from explants of F1 eyed eggs, F1 one year old fish gill and F1 two year old fish gill and spleen samples, and F2 two year old gill and spleen samples, as well as from bystander eggs/fish, was used to treat a reporter cell line, which was then assayed for changes in cellular survival/growth. The results were complex and dependent on irradiation history, age (in the case of the F1 generation), and were tissue specific. For example, irradiation of one parent often resulted in effects not seen with irradiation of both parents. This suggests that, unlike mammals, in certain circumstances maternal and paternal irradiation may be equally important. This study also showed that trout can induce a bystander effect 2 generations after irradiation, which further emphasises the importance of the bystander effect in aquatic radiobiology. Given the complex community structure in aquatic ecosystems, these results may have significant implications for environmental radiological protection. - Highlights: • We evaluated the transgenerational effect of early life irradiation in rainbow trout. • Trout irradiated as eggs, yolk sac larvae or first feeders were crossed. • A transgenerational effect was evident in two generations after irradiation. • F1 and F2 generation fish induced a bystander effect in non-irradiated fish. • The precise effects were tissue specific and dependent on

High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

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Thais de Castro Barbosa

2016-03-01

Conclusion: Our results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations.

Transgenerational changes in plant physiology and in transposon expression in response to UV-C stress in Arabidopsis thaliana.

Science.gov (United States)

Migicovsky, Zoe; Kovalchuk, Igor

2014-01-01

Stress has a negative impact on crop yield by altering a gain in biomass and affecting seed set. Recent reports suggest that exposure to stress also influences the response of the progeny. In this paper, we analyzed seed size, leaf size, bolting time and transposon expression in 2 consecutive generations of Arabidopsis thaliana plants exposed to moderate UV-C stress. Since previous reports suggested a potential role of Dicer-like (DCL) proteins in the establishment of transgenerational response, we used dcl2, dcl3 and dcl4 mutants in parallel with wild-type plants. These studies revealed that leaf number decreased in the progeny of UV-C stressed plants, and bolting occurred later. Transposons were also re-activated in the progeny of stressed plants. Changes in the dcl mutants were less prominent than in wild-type plants. DCL2 and DCL3 appeared to be more important in the transgenerational stress memory than DCL4 because transgenerational changes were less profound in the dcl2 and dcl3 mutants.

Transgenerational endpoints provide increased sensitivity and insight into multigenerational responses of Lymnaea stagnalis exposed to cadmium.

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Reátegui-Zirena, Evelyn G; Fidder, Bridgette N; Olson, Adric D; Dawson, Daniel E; Bilbo, Thomas R; Salice, Christopher J

2017-05-01

Ecotoxicology provides data to inform environmental management. Many testing protocols do not consider offspring fitness and toxicant sensitivity. Cadmium (Cd) is a well-studied and ubiquitous toxicant but little is known about the effects on offspring of exposed parents (transgenerational effects). This study had three objectives: to identify endpoints related to offspring performance; to determine whether parental effects would manifest as a change in Cd tolerance in offspring and how parental exposure duration influenced the manifestation of parental effects. Adult snails were exposed to Cd 0, 25, 50, 100, 200 and 400 μg Cd/L for eight weeks. There were effects on adult endpoints (e.g., growth, reproduction) but only at the highest concentrations (>100 μg/L). Alternatively, we observed significant transgenerational effects at all Cd concentrations. Surprisingly, we found increased Cd tolerance in hatchlings from all parental Cd exposure concentrations even though eggs and hatchlings were in Cd-free conditions for 6 weeks. Explicit consideration of offspring performance adds value to current toxicity testing protocols. Parental exposure duration has important implications for offspring effects and that contaminant concentrations that are not directly toxic to parents can cause transgenerational changes in resistance that have significant implications for toxicity testing and adaptive responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transgenerational Inheritance of Paternal Neurobehavioral Phenotypes: Stress, Addiction, Ageing and Metabolism.

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Yuan, Ti-Fei; Li, Ang; Sun, Xin; Ouyang, Huan; Campos, Carlos; Rocha, Nuno B F; Arias-Carrión, Oscar; Machado, Sergio; Hou, Gonglin; So, Kwok Fai

2016-11-01

Epigenetic modulation is found to get involved in multiple neurobehavioral processes. It is believed that different types of environmental stimuli could alter the epigenome of the whole brain or related neural circuits, subsequently contributing to the long-lasting neural plasticity of certain behavioral phenotypes. While the maternal influence on the health of offsprings has been long recognized, recent findings highlight an alternative way for neurobehavioral phenotypes to be passed on to the next generation, i.e., through the male germ line. In this review, we focus specifically on the transgenerational modulation induced by environmental stress, drugs of abuse, and other physical or mental changes (e.g., ageing, metabolism, fear) in fathers, and recapitulate the underlying mechanisms potentially mediating the alterations in epigenome or gene expression of offsprings. Together, these findings suggest that the inheritance of phenotypic traits through male germ-line epigenome may represent the unique manner of adaptation during evolution. Hence, more attention should be paid to the paternal health, given its equivalently important role in affecting neurobehaviors of descendants.

Adolescent opiate exposure in the female rat induces subtle alterations in maternal care and transgenerational effects on play behavior.

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Nicole L. Johnson

2011-06-01

Full Text Available The non-medical use of prescription opiates, such as Vicodin® and MSContin®, has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females’ spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1 demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e. social grooming and social exploration. Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal-offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

Ecdysone signaling underlies the pea aphid transgenerational wing polyphenism.

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Vellichirammal, Neetha Nanoth; Gupta, Purba; Hall, Tannice A; Brisson, Jennifer A

2017-02-07

The wing polyphenism of pea aphids is a compelling laboratory model with which to study the molecular mechanisms underlying phenotypic plasticity. In this polyphenism, environmental stressors such as high aphid density cause asexual, viviparous adult female aphids to alter the developmental fate of their embryos from wingless to winged morphs. This polyphenism is transgenerational, in that the pea aphid mother experiences the environmental signals, but it is her offspring that are affected. Previous research suggested that the steroid hormone ecdysone may play a role in this polyphenism. Here, we analyzed ecdysone-related gene expression patterns and found that they were consistent with a down-regulation of the ecdysone pathway being involved in the production of winged offspring. We therefore predicted that reduced ecdysone signaling would result in more winged offspring. Experimental injections of ecdysone or its analog resulted in a decreased production of winged offspring. Conversely, interfering with ecdysone signaling using an ecdysone receptor antagonist or knocking down the ecdysone receptor gene with RNAi resulted in an increased production of winged offspring. Our results are therefore consistent with the idea that ecdysone plays a causative role in the regulation of the proportion of winged offspring produced in response to crowding in this polyphenism. Our results also show that an environmentally regulated maternal hormone can mediate phenotype production in the next generation, as well as provide significant insight into the molecular mechanisms underlying the functioning of transgenerational phenotypic plasticity.

"Trans-generational immune priming": specific enhancement of the antimicrobial immune response in the mealworm beetle, Tenebrio molitor.

Science.gov (United States)

Moret, Yannick

2006-06-07

Encounters with parasites and pathogens are often unpredictable in time. However, experience of an infection may provide the host with reliable cues about the future risk of infection for the host itself or for its progeny. If the parental environment predicts the quality of the progeny's environment, then parents may further enhance their net reproductive success by differentially providing their offspring with phenotypes to cope with potential hazards such as pathogen infection. Here, I test for the occurrence of such an adaptive transgenerational phenotypic plasticity in the mealworm beetle, Tenebrio molitor. A pathogenic environment was mimicked by injection of bacterial lipopolysaccharides for two generations of insects. I found that parental challenge enhanced offspring immunity through the inducible production of antimicrobial peptides in the haemolymph.

Within- and Trans-Generational Effects of Variation in Dietary Macronutrient Content on Life-History Traits in the Moth Plodia interpunctella

Science.gov (United States)

Knell, Robert J.

2016-01-01

It is increasingly clear that parental environment can play an important role in determining offspring phenotype. These “transgenerational effects” have been linked to many different components of the environment, including toxin exposure, infection with pathogens and parasites, temperature and food quality. In this study, we focus on the latter, asking how variation in the quantity and quality of nutrition affects future generations. Previous studies have shown that artificial diets are a useful tool to examine the within-generation effects of variation in macronutrient content on life history traits, and could therefore be applied to investigations of the transgenerational effects of parental diet. Synthetic diets varying in total macronutrient content and protein: carbohydrate ratios were used to examine both within- and trans-generational effects on life history traits in a generalist stored product pest, the Indian meal moth Plodia interpunctella. The macronutrient composition of the diet was important for shaping within-generation life history traits, including pupal weight, adult weight, and phenoloxidase activity, and had indirect effects via maternal weight on fecundity. Despite these clear within-generation effects on the biology of P. interpunctella, diet composition had no transgenerational effects on the life history traits of offspring. P. interpunctella mothers were able to maintain their offspring quality, possibly at the expense of their own somatic condition, despite high variation in dietary macronutrient composition. This has important implications for the plastic biology of this successful generalist pest. PMID:28033396

Within- and Trans-Generational Effects of Variation in Dietary Macronutrient Content on Life-History Traits in the Moth Plodia interpunctella.

Directory of Open Access Journals (Sweden)

Joanne E Littlefair

Full Text Available It is increasingly clear that parental environment can play an important role in determining offspring phenotype. These "transgenerational effects" have been linked to many different components of the environment, including toxin exposure, infection with pathogens and parasites, temperature and food quality. In this study, we focus on the latter, asking how variation in the quantity and quality of nutrition affects future generations. Previous studies have shown that artificial diets are a useful tool to examine the within-generation effects of variation in macronutrient content on life history traits, and could therefore be applied to investigations of the transgenerational effects of parental diet. Synthetic diets varying in total macronutrient content and protein: carbohydrate ratios were used to examine both within- and trans-generational effects on life history traits in a generalist stored product pest, the Indian meal moth Plodia interpunctella. The macronutrient composition of the diet was important for shaping within-generation life history traits, including pupal weight, adult weight, and phenoloxidase activity, and had indirect effects via maternal weight on fecundity. Despite these clear within-generation effects on the biology of P. interpunctella, diet composition had no transgenerational effects on the life history traits of offspring. P. interpunctella mothers were able to maintain their offspring quality, possibly at the expense of their own somatic condition, despite high variation in dietary macronutrient composition. This has important implications for the plastic biology of this successful generalist pest.

Within- and Trans-Generational Effects of Variation in Dietary Macronutrient Content on Life-History Traits in the Moth Plodia interpunctella.

Science.gov (United States)

Littlefair, Joanne E; Knell, Robert J

2016-01-01

It is increasingly clear that parental environment can play an important role in determining offspring phenotype. These "transgenerational effects" have been linked to many different components of the environment, including toxin exposure, infection with pathogens and parasites, temperature and food quality. In this study, we focus on the latter, asking how variation in the quantity and quality of nutrition affects future generations. Previous studies have shown that artificial diets are a useful tool to examine the within-generation effects of variation in macronutrient content on life history traits, and could therefore be applied to investigations of the transgenerational effects of parental diet. Synthetic diets varying in total macronutrient content and protein: carbohydrate ratios were used to examine both within- and trans-generational effects on life history traits in a generalist stored product pest, the Indian meal moth Plodia interpunctella. The macronutrient composition of the diet was important for shaping within-generation life history traits, including pupal weight, adult weight, and phenoloxidase activity, and had indirect effects via maternal weight on fecundity. Despite these clear within-generation effects on the biology of P. interpunctella, diet composition had no transgenerational effects on the life history traits of offspring. P. interpunctella mothers were able to maintain their offspring quality, possibly at the expense of their own somatic condition, despite high variation in dietary macronutrient composition. This has important implications for the plastic biology of this successful generalist pest.

Developmental systems of plasticity and trans-generational epigenetic inheritance in nematodes.

Science.gov (United States)

Serobyan, Vahan; Sommer, Ralf J

2017-08-01

Several decades of research provided detailed insight into how genes control development and evolution, whereas recent studies have expanded this purely genetic perspective by presenting strong evidence for environmental and epigenetic influences. We summarize examples of phenotypic plasticity and trans-generational epigenetic inheritance in the nematode model organisms Pristionchus pacificus and Caenorhabditis elegans, which indicate that the response of developmental systems to environmental influences is hardwired into the organismś genome. We argue that genetic programs regulating these organismal-environmental interactions are themselves subject to natural selection. Indeed, macro-evolutionary studies of nematode feeding structures indicate evolutionary trajectories in which plasticity followed by genetic assimilation results in extreme diversity highlighting the role of plasticity as major facilitator of phenotypic diversification. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adiposopathy and epigenetics: an introduction to obesity as a transgenerational disease.

Science.gov (United States)

Bays, Harold; Scinta, Wendy

2015-11-01

To examine the contribution of generational epigenetic dysregulation to the inception of obesity and its adiposopathic consequences. Sources for this review included searches of PubMed, Google Scholar, and international government/major association websites using terms including adiposity, adiposopathy, epigenetics, genetics, and obesity. Excessive energy storage in adipose tissue often results in fat cell and fat organ dysfunction, which may cause metabolic and fat mass disorders. The adverse clinical manifestations of obesity are not solely due to the amount of body fat (adiposity), but are also dependent on anatomical and functional perturbations (adiposopathy or 'sick fat'). This review describes extragenetic factors and genetic conditions that promote obesity. It also serves as an introduction to epigenetic dysregulation (i.e., abnormalities in gene expression that occur without alteration in the genetic code itself), which may contribute to obesity and adiposopathic metabolic health outcomes in offspring. Within the epigenetic paradigm, obesity is a transgenerational disease, with weight lost or gained by either parent potentially impacting generational risk for obesity and its complications. Epigenetics may be an important contributor to the emergence of obesity and its complications as global epidemics. Although transgenerational epigenetic influences present challenges, they may also present interventional opportunities, via justifying weight management for individuals before, during, and after pregnancy and for future generations.

Trans-generational effect of radiation. Finding a tomorrow guide by the past lessons

International Nuclear Information System (INIS)

Yamauchi, Masatake

2004-01-01

This review describes findings concerning the trans-generational effect of radiation in animals and man. In experimental animals, there are findings of the effect in Drosophila irradiated by X-ray in 1927 and in mice by X- and gamma rays in 1982. Thereafter, many studies have been done on genetic stability of hypervariable minisatellite locus Ms6-hm in mice. In man, epidemiological findings are related with the effect. Although many studies are conducted on the epidemiology of people living in the high background radiation areas in China, of leukemia in radiation-exposed father's children, of Japanese A-bomb survivors and their descendants, and of people after Chernobyl accident, a possible trans-generational effect has been seen only in one of reports concerned with Chernobyl accident. Dynamic mutations of regions of hypervariable repeated sequence in man are discussed in relation with its genetic instability associated with hereditary diseases like fragile X syndrome. The author mentions that findings of the effect should provide answers for people's anxiety and questions. (N.I.)

Transgenerational effects of radiation and chemicals in mice and humans

International Nuclear Information System (INIS)

Nomura, Taisei

2006-01-01

Parental exposure of mice to radiation and chemicals causes a variety of adverse effects (e.g., tumors, congenital malformations and embryonic deaths) in the progeny and the tumor-susceptibility phenotype is transmissible beyond the first post-radiation generation. The induced rates of tumors were 100-fold higher than those known for mouse specific locus mutations. There were clear strain differences in the types of naturally-occurring and induced tumors and most of the latter were malignant. Another important finding was that germ-line exposure elicited very weak tumorigenic responses, but caused persistent hypersensitivity in the offspring for the subsequent development of cancer by the postnatal environment. Activations of oncogenes, ras, mos, abl, etc. and mutations in tumor suppressor genes such as p53 were also detected in specific tumors in cancer-prone descendants. However, the majority of tumors observed in the progeny were those commonly observed in the strains that were used and oncogene activations were rarely observed in these tumors. It can be hypothesized that genetic instability modifies tumor occurrence in a transgenerational manner, but so far no links could be established between chromosomal and molecular changes and transmissible tumor risks. Our data are consistent with the hypothesis that cumulative changes in many normal but cancer-related genes affecting immunological, biochemical and physiological functions may slightly elevate the incidence of tumors or fasten the tumor development. This hypothesis is supported by our GeneChip analyses which showed suppression and/or over-expression of many such genes in the offspring of mice exposed to radiation. In humans, a higher risk of leukemia and birth defects has been reported in the children of fathers who had been exposed to radionuclides in the nuclear reprocessing plants and to diagnostic radiation. These findings have not been supported in the children of atomic bomb survivors in Hiroshima

Transgenerational plasticity following a dual pathogen and stress challenge in fruit flies

OpenAIRE

Nystrand, M.; Cassidy, E. J.; Dowling, D. K.

2016-01-01

Background Phenotypic plasticity operates across generations, when the parental environment affects phenotypic expression in the offspring. Recent studies in invertebrates have reported transgenerational plasticity in phenotypic responses of offspring when the mothers had been previously exposed to either live or heat-killed pathogens. Understanding whether this plasticity is adaptive requires a factorial design in which both mothers and their offspring are subjected to either the pathogen ch...

Ingestional and transgenerational effects of the Fukushima nuclear accident on the pale grass blue butterfly

International Nuclear Information System (INIS)

Taira, Wataru; Hiyama, Atsuki; Nohara, Chiyo; Sakauchi, Ko; Otaki, Joji M.

2015-01-01

One important public concern in Japan is the potential health effects on animals and humans that live in the Tohoku-Kanto districts associated with the ingestion of foods contaminated with artificial radionuclides from the collapsed Fukushima Dai-ichi Nuclear Power Plant. Additionally, transgenerational or heritable effects of radiation exposure are also important public concerns because these effects could cause long-term changes in animal and human populations. Here, we concisely review our findings and implications related to the ingestional and transgenerational effects of radiation exposure on the pale grass blue butterfly, Zizeeria maha, which coexists with humans. The butterfly larval ingestion of contaminated leaves found in areas of human habitation, even at low doses, resulted in morphological abnormalities and death for some individuals, whereas other individuals were not affected, at least morphologically. This variable sensitivity serves as a basis for the adaptive evolution of radiation resistance. The distribution of abnormality and mortality rates from low to high doses fits well with a Weibull function model or a power function model. The offspring generated by morphologically normal individuals that consumed contaminated leaves exhibited high mortality rates when fed contaminated leaves; importantly, low mortality rates were restored when they were fed non-contaminated leaves. Our field monitoring over 3 years (2011–2013) indicated that abnormality and mortality rates peaked primarily in the fall of 2011 and decreased afterwards to normal levels. These findings indicate high impacts of early exposure and transgenerationally accumulated radiation effects over a specific period; however, the population regained normality relatively quickly after ∼15 generations within 3 years

Transgenerational effects persist down the maternal line in marine sticklebacks: gene expression matches physiology in a warming ocean.

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Shama, Lisa N S; Mark, Felix C; Strobel, Anneli; Lokmer, Ana; John, Uwe; Mathias Wegner, K

2016-10-01

Transgenerational effects can buffer populations against environmental change, yet little is known about underlying mechanisms, their persistence or the influence of environmental cue timing. We investigated mitochondrial respiratory capacity (MRC) and gene expression of marine sticklebacks that experienced acute or developmental acclimation to simulated ocean warming (21°C) across three generations. Previous work showed that acute acclimation of grandmothers to 21°C led to lower (optimized) offspring MRCs. Here, developmental acclimation of mothers to 21°C led to higher, but more efficient offspring MRCs. Offspring with a 21°C × 17°C grandmother-mother environment mismatch showed metabolic compensation: their MRCs were as low as offspring with a 17°C thermal history across generations. Transcriptional analyses showed primarily maternal but also grandmaternal environment effects: genes involved in metabolism and mitochondrial protein biosynthesis were differentially expressed when mothers developed at 21°C, whereas 21°C grandmothers influenced genes involved in hemostasis and apoptosis. Genes involved in mitochondrial respiration all showed higher expression when mothers developed at 21° and lower expression in the 21°C × 17°C group, matching the phenotypic pattern for MRCs. Our study links transcriptomics to physiology under climate change, and demonstrates that mechanisms underlying transgenerational effects persist across multiple generations with specific outcomes depending on acclimation type and environmental mismatch between generations.

Brief Communication: Sexual dimorphic expression of myostatin and follistatin like-3 in a rat trans-generational under-nutrition model

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Mitchell Murray D

2010-05-01

Full Text Available Abstract The detrimental effects of maternal under-nutrition during gestation on fetal development are well known with an increased propensity of metabolic disorders identified in the adult offspring. Understanding exactly how and by which molecular pathways inadequate nutrition can impact upon offspring phenotype is critical and necessary for the development of treatment methods and ultimately prevention of any negative health effects. Myostatin, a negative regulator of muscle development, has recently been shown to effect glucose homeostasis and fat deposition. The involvement of myostatin in glucose metabolism and adipogenesis thus supports its ability to act in the continued alterations to the postnatal phenotype of the offspring. This hypothesis was examined in the current study using a trans-generational gestationally under-nourished rat model exposed to a high-fat (HF diet post-weaning. The body weight, body fat, plasma glucose and insulin concentrations of the offspring, both male and female, were investigated in relation to the protein expression of myostatin and its main inhibitor; follistatin like-3 (FSTL-3, in skeletal muscle of mature offspring. Sexual dimorphism was clearly evident in the majority of these measures, including myostatin and FSTL-3 expression. Generally males displayed higher (P myostatin precursor and dimer expression than females, which was especially apparent (P in both chow and HF trans-generationally undernourished (UNAD groups. In females only, myostatin precursor and dimer expression was altered by both trans-generational under-nutrition and postnatal diet. Overall FSTL-3 expression did not differ between sexes, although difference between sexes within certain treatments and diets were evident. Most notably, HF fed UNAD females had higher (P FSTL-3 expression than HF fed UNAD males. The former group also displayed higher (P FSTL-3 expression compared to all other female groups. In summary, myostatin may prove

Transgenerational effects of prenatal bisphenol A on social recognition.

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Wolstenholme, Jennifer T; Goldsby, Jessica A; Rissman, Emilie F

2013-11-01

Bisphenol A (BPA) is a man-made endocrine disrupting compound used to manufacture polycarbonate plastics. It is found in plastic bottles, canned food linings, thermal receipts and other commonly used items. Over 93% of people have detectable BPA levels in their urine. Epidemiological studies report correlations between BPA levels during pregnancy and activity, anxiety, and depression in children. We fed female mice control or BPA-containing diets that produced plasma BPA concentrations similar to concentrations in humans. Females were mated and at birth, pups were fostered to control dams to limit BPA exposure to gestation in the first generation. Sibling pairs were bred to the third generation with no further BPA exposure. First (F1) and third (F3) generation juveniles were tested for social recognition and in the open field. Adult F3 mice were tested for olfactory discrimination. In both generations, BPA exposed juvenile mice displayed higher levels of investigation than controls in a social recognition task. In F3 BPA exposed mice, dishabituation to a novel female was impaired. In the open field, no differences were noted in F1 mice, while in F3, BPA lineage mice were more active than controls. No impairments were detected in F3 mice, all were able to discriminate different male urine pools and urine from water. No sex differences were found in any task. These results demonstrate that BPA exposure during gestation has long lasting, transgenerational effects on social recognition and activity in mice. These findings show that BPA exposure has transgenerational actions on behavior and have implications for human neurodevelopmental behavioral disorders. © 2013.

Can transgenerational plasticity contribute to the invasion success of annual plant species?

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Fenesi, Annamária; Dyer, Andrew R; Geréd, Júliánna; Sándor, Dorottya; Ruprecht, Eszter

2014-09-01

Adaptive transgenerational plasticity (TGP), i.e., significantly higher fitness when maternal and offspring conditions match, might contribute to the population growth of non-native species in highly variable environments. However, comparative studies that directly test this hypothesis are lacking. Therefore, we performed a reciprocal split-brood experiment to compare TGP in response to N and water availability in single populations of two invasive (Amaranthus retroflexus, Galinsoga parviflora) and two congeneric non-invasive introduced species (Amaranthus albus, Galinsoga ciliata). We hypothesized that the transgenerational effect is adaptive: (1) in invasive species compared with non-invasive adventives, and (2) in stressful conditions compared with resource-rich environments. The phenotypic variation among offspring was generated, in large part, by our experimental treatments in the maternal generation; therefore, we demonstrated a direct TGP effect on the offspring's adult fitness. We found evidence, for the first time, that invasive and non-invasive adventive species differ regarding the expression of TGP in the adult stage, as adaptive responses were found exclusively in the invasive species. The manifestation of TGP was more explicit under resource-rich conditions; therefore, it might contribute to the population dynamics of non-native species in resource-rich sites rather than to their ecological tolerance spectra.

Transgenerational effects of mild heat in Arabidopsis thaliana show strong genotype specificity that is explained by climate at origin.

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Groot, Maartje P; Kubisch, Alexander; Ouborg, N Joop; Pagel, Jörn; Schmid, Karl J; Vergeer, Philippine; Lampei, Christian

2017-08-01

Transgenerational environmental effects can trigger strong phenotypic variation. However, it is unclear how cues from different preceding generations interact. Also, little is known about the genetic variation for these life history traits. Here, we present the effects of grandparental and parental mild heat, and their combination, on four traits of the third-generation phenotype of 14 Arabidopsis thaliana genotypes. We tested for correlations of these effects with climate and constructed a conceptual model to identify the environmental conditions that favour the parental effect on flowering time. We observed strong evidence for genotype-specific transgenerational effects. On average, A. thaliana accustomed to mild heat produced more seeds after two generations. Parental effects overruled grandparental effects in all traits except reproductive biomass. Flowering was generally accelerated by all transgenerational effects. Notably, the parental effect triggered earliest flowering in genotypes adapted to dry summers. Accordingly, this parental effect was favoured in the model when early summer heat terminated the growing season and environments were correlated across generations. Our results suggest that A. thaliana can partly accustom to mild heat over two generations and genotype-specific parental effects show non-random evolutionary divergence across populations that may support climate change adaptation in the Mediterranean. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Stress transgenerationally programs metabolic pathways linked to altered mental health.

Science.gov (United States)

Kiss, Douglas; Ambeskovic, Mirela; Montina, Tony; Metz, Gerlinde A S

2016-12-01

Stress is among the primary causes of mental health disorders, which are the most common reason for disability worldwide. The ubiquity of these disorders, and the costs associated with them, lends a sense of urgency to the efforts to improve prediction and prevention. Down-stream metabolic changes are highly feasible and accessible indicators of pathophysiological processes underlying mental health disorders. Here, we show that remote and cumulative ancestral stress programs central metabolic pathways linked to mental health disorders. The studies used a rat model consisting of a multigenerational stress lineage (the great-great-grandmother and each subsequent generation experienced stress during pregnancy) and a transgenerational stress lineage (only the great-great-grandmother was stressed during pregnancy). Urine samples were collected from adult male F4 offspring and analyzed using 1 H NMR spectroscopy. The results of variable importance analysis based on random variable combination were used for unsupervised multivariate principal component analysis and hierarchical clustering analysis, as well as metabolite set enrichment analysis (MSEA) and pathway analysis. We identified distinct metabolic profiles associated with the multigenerational and transgenerational stress phenotype, with consistent upregulation of hippurate and downregulation of tyrosine, threonine, and histamine. MSEA and pathway analysis showed that these metabolites are involved in catecholamine biosynthesis, immune responses, and microbial host interactions. The identification of metabolic signatures linked to ancestral programming assists in the discovery of gene targets for future studies of epigenetic regulation in pathogenic processes. Ultimately, this research can lead to biomarker discovery for better prediction and prevention of mental health disorders.

ALTERATIONS IN THE DEVELOPING TESTIS TRANSCRIPTOME FOLLOWING EMBRYONIC VINCLOZOLIN EXPOSURE

OpenAIRE

Clement, Tracy M.; Savenkova, Marina I.; Settles, Matthew; Anway, Matthew D.; Skinner, Michael K.

2010-01-01

The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 di...

Multigenerational contaminant exposures produce non-monotonic, transgenerational responses in Daphnia magna

International Nuclear Information System (INIS)

Kimberly, David A.; Salice, Christopher J.

2015-01-01

Generally, ecotoxicologists rely on short-term tests that assume populations to be static. Conversely, natural populations may be exposed to the same stressors for many generations, which can alter tolerance to the same (or other) stressors. The objective of this study was to improve our understanding of how multigenerational stressors alter life history traits and stressor tolerance. After continuously exposing Daphnia magna to cadmium for 120 days, we assessed life history traits and conducted a challenge at higher temperature and cadmium concentrations. Predictably, individuals exposed to cadmium showed an overall decrease in reproductive output compared to controls. Interestingly, control D. magna were the most cadmium tolerant to novel cadmium, followed by those exposed to high cadmium. Our data suggest that long-term exposure to cadmium alter tolerance traits in a non-monotonic way. Because we observed effects after one-generation removal from cadmium, transgenerational effects may be possible as a result of multigenerational exposure. - Highlights: • Daphnia magna exposed to cadmium for 120 days. • D. magna exposed to cadmium had decreased reproductive output. • Control D. magna were most cadmium tolerant to novel cadmium stress. • Long-term exposure to cadmium alter tolerance traits in a non-monotonic way. • Transgenerational effects observed as a result of multigenerational exposure. - Adverse effects of long-term cadmium exposure persist into cadmium free conditions, as seen by non-monotonic responses when exposed to novel stress one generation removed.

The effects of maternal irradiation during adulthood on mutation induction and transgenerational instability in mice

International Nuclear Information System (INIS)

Abouzeid Ali, Hamdy E.; Barber, Ruth C.; Dubrova, Yuri E.

2012-01-01

The long-term genetic effects of maternal irradiation remain poorly understood. To establish the effects of radiation exposure on mutation induction in the germline of directly exposed females and the possibility of transgenerational effects in their non-exposed offspring, adult female BALB/c and CBA/Ca mice were given 1 Gy of acute X-rays and mated with control males. The frequency of mutation at expanded simple tandem repeat (ESTR) loci in the germline of directly exposed females did not differ from that of controls. Using a single-molecule PCR approach, ESTR mutation frequency was also established for both germline and somatic tissues in the first-generation offspring of irradiated parents. While the frequency of ESTR mutation in the offspring of irradiated males was significantly elevated, maternal irradiation did not affect stability in their F 1 offspring. Considering these data and the results of our previous study, we propose that, in sharp contrast to paternal exposure to ionising radiation, the transgenerational effects of maternal high-dose acute irradiation are likely to be negligible.

Transgenerational epigenetics: Inheritance of global cytosine methylation and methylation-related epigenetic markers in the shrub Lavandula latifolia.

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Herrera, Carlos M; Alonso, Conchita; Medrano, Mónica; Pérez, Ricardo; Bazaga, Pilar

2018-04-01

The ecological and evolutionary significance of natural epigenetic variation (i.e., not based on DNA sequence variants) variation will depend critically on whether epigenetic states are transmitted from parents to offspring, but little is known on epigenetic inheritance in nonmodel plants. We present a quantitative analysis of transgenerational transmission of global DNA cytosine methylation (= proportion of all genomic cytosines that are methylated) and individual epigenetic markers (= methylation status of anonymous MSAP markers) in the shrub Lavandula latifolia. Methods based on parent-offspring correlations and parental variance component estimation were applied to epigenetic features of field-growing plants ('maternal parents') and greenhouse-grown progenies. Transmission of genetic markers (AFLP) was also assessed for reference. Maternal parents differed significantly in global DNA cytosine methylation (range = 21.7-36.7%). Greenhouse-grown maternal families differed significantly in global methylation, and their differences were significantly related to maternal origin. Methylation-sensitive amplified polymorphism (MSAP) markers exhibited significant transgenerational transmission, as denoted by significant maternal variance component of marker scores in greenhouse families and significant mother-offspring correlations of marker scores. Although transmission-related measurements for global methylation and MSAP markers were quantitatively lower than those for AFLP markers taken as reference, this study has revealed extensive transgenerational transmission of genome-wide global cytosine methylation and anonymous epigenetic markers in L. latifolia. Similarity of results for global cytosine methylation and epigenetic markers lends robustness to this conclusion, and stresses the value of considering both types of information in epigenetic studies of nonmodel plants. © 2018 Botanical Society of America.

Environmentally induced transgenerational changes in seed longevity: maternal and genetic influence.

Science.gov (United States)

Mondoni, A; Orsenigo, S; Donà, M; Balestrazzi, A; Probert, R J; Hay, F R; Petraglia, A; Abeli, T

2014-06-01

Seed longevity, a fundamental plant trait for ex situ conservation and persistence in the soil of many species, varies across populations and generations that experience different climates. This study investigates the extent to which differences in seed longevity are due to genetic differences and/or modified by adaptive responses to environmental changes. Seeds of two wild populations of Silene vulgaris from alpine (wA) and lowland (wL) locations and seeds originating from their cultivation in a lowland common garden for two generations (cA1, cL1, cA2 and cL2) were exposed to controlled ageing at 45 °C, 60 % relative humidity and regularly sampled for germination and relative mRNA quantification (SvHSP17.4 and SvNRPD12). The parental plant growth environment affected the longevity of seeds with high plasticity. Seeds of wL were significantly longer lived than those of wA. However, when alpine plants were grown in the common garden, longevity doubled for the first generation of seeds produced (cA1). Conversely, longevity was similar in all lowland seed lots and did not increase in the second generation of seeds produced from alpine plants grown in the common garden (cA2). Analysis of parental effects on mRNA seed provisioning indicated that the accumulation of gene transcripts involved in tolerance to heat stress was highest in wL, cL1 and cL2, followed by cA1, cA2 and wA. Seed longevity has a genetic basis, but may show strong adaptive responses, which are associated with differential accumulation of mRNA via parental effects. Adaptive adjustments of seed longevity due to transgenerational plasticity may play a fundamental role in the survival and persistence of the species in the face of future environmental challenges. The results suggest that regeneration location may have important implications for the conservation of alpine plants held in seed banks. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All

Perception of transgenerational family relationships: Comparison of eating-disordered patients and their parents

OpenAIRE

Pilecki, Maciej Wojciech; J?zefik, Barbara

2013-01-01

Background Disturbances in various elements of transgenerational family functioning patterns are not uncommon in studies of eating disorders. We examined the relationship between patients? perception of autonomy and intimacy in their families of origin and that of their parents in their own families of origin. Material/Methods The sample consisted of 112 girls who had a diagnosis of an eating disoder and their parents; 54 of the girls were diagnosed with anorexia nervosa restrictive subtype, ...

Roads Leading to Self-Employment: Comparing Transgenerational Entrepreneurs and Self-Made Start-Ups

OpenAIRE

Blumberg, Boris; Pfann, Gerard Antonie

2015-01-01

This paper studies the event history of business foundation and distinguishes between transgenerational entrepreneurship and self-made start-ups. Three theoretical concepts of human, financial and social capital are linked to investigate variations over time in the decision process to become self-employed. Data from a cohort of Dutch inhabitants born in 1939/1940 who have been interviewed three times during their lives in 1952, 1983, and 1993 allows testing theoretical hypotheses that state c...

Transgenerational stress memory is not a general response in Arabidopsis.

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Ales Pecinka

Full Text Available Adverse conditions can trigger DNA damage as well as DNA repair responses in plants. A variety of stress factors are known to stimulate homologous recombination, the most accurate repair pathway, by increasing the concentration of necessary enzymatic components and the frequency of events. This effect has been reported to last into subsequent generations not exposed to the stress. To establish a basis for a genetic analysis of this transgenerational stress memory, a broad range of treatments was tested for quantitative effects on homologous recombination in the progeny. Several Arabidopsis lines, transgenic for well-established recombination traps, were exposed to 10 different physical and chemical stress treatments, and scored for the number of somatic homologous recombination (SHR events in the treated generation as well as in the two subsequent generations that were not treated. These numbers were related to the expression level of genes involved in homologous recombination and repair. SHR was enhanced after the majority of treatments, confirming previous data and adding new effective stress types, especially interference with chromatin. Compounds that directly modify DNA stimulated SHR to values exceeding previously described induction rates, concomitant with an induction of genes involved in SHR. In spite of the significant stimulation in the stressed generations, the two subsequent non-treated generations only showed a low and stochastic increase in SHR that did not correlate with the degree of stimulation in the parental plants. Transcripts coding for SHR enzymes generally returned to pre-treatment levels in the progeny. Thus, transgenerational effects on SHR frequency are not a general response to abiotic stress in Arabidopsis and may require special conditions.

Natural dissolved humic substances increase the lifespan and promote transgenerational resistance to salt stress in the cladoceran Moina macrocopa.

Science.gov (United States)

Suhett, Albert L; Steinberg, Christian E W; Santangelo, Jayme M; Bozelli, Reinaldo L; Farjalla, Vinicius F

2011-07-01

Evidence has accumulated that humic substances (HS) are not inert biogeochemicals. Rather, they cause stress symptoms and may modulate the life history of aquatic organisms. Nevertheless, it is still not clear how HS interact with additional stressors and if their effects are transgenerational. We tested the interactive effects of HS and salt to cladocerans, discussing their consequences for the persistence in fluctuating environments, such as coastal lagoons. We used life-table experiments to test the effects of natural HS from a polyhumic coastal lagoon (0, 5, 10, 20, 50, and 100 mg dissolved organic carbon (DOC) L(-1)) on the life-history of the cladoceran Moina macrocopa. We further tested the effects of HS (10 mg DOC L(-1)), within and across generations, on the resistance of M. macrocopa to salt stress (5.5 g L(-1)). HS at 5-20 mg DOC L(-1) extended the mean lifespan of M. macrocopa by ~30%. HS also increased body length at maturity by ~4% at 5-50 mg DOC L(-1) and stimulated male offspring production at all tested concentrations. Exposure to HS (even maternal only) alleviated the salt-induced reduction of somatic growth. Co-exposure to HS increased body volume by 12-22% relative to salt-only treatments, while pre-exposure to HS increased body volume by 40-56% in treatments with salt presence, when compared to non-pre-exposed animals. HS at environmentally realistic concentrations, by acting as mild chemical stressors, modify crucial life-history traits of M. macrocopa, favoring its persistence in fluctuating environments. Some of the effects of HS are even transgenerational.

Long-Term Overgrazing-Induced Memory Decreases Photosynthesis of Clonal Offspring in a Perennial Grassland Plant.

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Ren, Weibo; Hu, Ningning; Hou, Xiangyang; Zhang, Jize; Guo, Huiqin; Liu, Zhiying; Kong, Lingqi; Wu, Zinian; Wang, Hui; Li, Xiliang

2017-01-01

Previous studies of transgenerational plasticity have demonstrated that long-term overgrazing experienced by Leymus chinensis , an ecologically dominant, rhizomatous grass species in eastern Eurasian temperate grassland, significantly affects its clonal growth in subsequent generations. However, there is a dearth of information on the reasons underlying this overgrazing-induced memory effect in plant morphological plasticity. We characterized the relationship between a dwarf phenotype and photosynthesis function decline of L. chinensis from the perspective of leaf photosynthesis by using both field measurement and rhizome buds culture cultivated in a greenhouse. Leaf photosynthetic functions (net photosynthetic rate, stomatal conductance, intercellular carbon dioxide concentration, and transpiration rate) were significantly decreased in smaller L. chinensis individuals that were induced to have a dwarf phenotype by being heavily grazed in the field. This decreased photosynthetic function was maintained a generation after greenhouse tests in which grazing was excluded. Both the response of L. chinensis morphological traits and photosynthetic functions in greenhouse were deceased relative to those in the field experiment. Further, there were significant decreases in leaf chlorophyll content and Rubisco enzyme activities of leaves between bud-cultured dwarf and non-dwarf L. chinensis in the greenhouse. Moreover, gene expression patterns showed that the bud-cultured dwarf L. chinensis significantly down-regulated (by 1.86- to 5.33-fold) a series of key genes that regulate photosynthetic efficiency, stomata opening, and chloroplast development compared with the non-dwarf L. chinensis . This is among the first studies revealing a linkage between long-term overgrazing affecting the transgenerational morphological plasticity of clonal plants and physiologically adaptive photosynthesis function. Overall, clonal transgenerational effects in L. chinensis phenotypic traits

Long-Term Overgrazing-Induced Memory Decreases Photosynthesis of Clonal Offspring in a Perennial Grassland Plant

Directory of Open Access Journals (Sweden)

Xiangyang Hou

2017-04-01

Full Text Available Previous studies of transgenerational plasticity have demonstrated that long-term overgrazing experienced by Leymus chinensis, an ecologically dominant, rhizomatous grass species in eastern Eurasian temperate grassland, significantly affects its clonal growth in subsequent generations. However, there is a dearth of information on the reasons underlying this overgrazing-induced memory effect in plant morphological plasticity. We characterized the relationship between a dwarf phenotype and photosynthesis function decline of L. chinensis from the perspective of leaf photosynthesis by using both field measurement and rhizome buds culture cultivated in a greenhouse. Leaf photosynthetic functions (net photosynthetic rate, stomatal conductance, intercellular carbon dioxide concentration, and transpiration rate were significantly decreased in smaller L. chinensis individuals that were induced to have a dwarf phenotype by being heavily grazed in the field. This decreased photosynthetic function was maintained a generation after greenhouse tests in which grazing was excluded. Both the response of L. chinensis morphological traits and photosynthetic functions in greenhouse were deceased relative to those in the field experiment. Further, there were significant decreases in leaf chlorophyll content and Rubisco enzyme activities of leaves between bud-cultured dwarf and non-dwarf L. chinensis in the greenhouse. Moreover, gene expression patterns showed that the bud-cultured dwarf L. chinensis significantly down-regulated (by 1.86- to 5.33-fold a series of key genes that regulate photosynthetic efficiency, stomata opening, and chloroplast development compared with the non-dwarf L. chinensis. This is among the first studies revealing a linkage between long-term overgrazing affecting the transgenerational morphological plasticity of clonal plants and physiologically adaptive photosynthesis function. Overall, clonal transgenerational effects in L. chinensis

Disease load at conception predicts survival in later epidemics in a historical French-Canadian cohort, suggesting functional trans-generational effects in humans.

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Kai Willführ

Full Text Available OBJECTIVE: Functional trans-generational and parental effects are potentially important determinants of health in several mammals. For humans, the existing evidence is weak. We investigate whether disease exposure triggers functional trans-generational response effects among humans by analyzing siblings who were conceived under different disease loads, and comparing their mortality in later epidemics. Under functional trans-generational response mechanisms, we expect that those who were conceived under high pathogenic stress load will have relatively low mortality during a later epidemic. METHODS: We use data from the Registre de la Population du Québec Ancien, which covers the historical population living in St. Lawrence Valley, Québec, Canada. Children born in 1705-1724 were grouped according to their exposure during conception to the measles 1714-15 epidemic. The 1714-15 epidemic was followed by two mortality crises in 1729-1734. The cause of the first crises in 1729 is not exactly known. The second crisis in 1732 was caused by a smallpox epidemic. Using proportional hazard Cox regression models with multivariate adjustment and with fixed-effects approach that compare siblings, we analyze whether mortality in 1729-1734 is affected by exposure to the 1714-15 epidemic. RESULTS: Children who were conceived during the peak of the measles epidemic of 1714-15 exhibited significantly lower mortality during the 1729-1734 crisis than those who were born before the 1714-15 epidemic (mortality hazard ratio 0.106, p<.05 in multivariate adjusted models; 0.142 p<.1 in sibling comparison models. CONCLUSIONS: The results are consistent with a trans-generational mechanism that functionally responds to pathogen stress and suggest that early disease exposure may be protective later in life. Alternative explanations for the mortality patterns are discussed and shown to be problematic.

The influence of DNA sequence on epigenome-induced pathologies

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Meagher Richard B

2012-07-01

Full Text Available Abstract Clear cause-and-effect relationships are commonly established between genotype and the inherited risk of acquiring human and plant diseases and aberrant phenotypes. By contrast, few such cause-and-effect relationships are established linking a chromatin structure (that is, the epitype with the transgenerational risk of acquiring a disease or abnormal phenotype. It is not entirely clear how epitypes are inherited from parent to offspring as populations evolve, even though epigenetics is proposed to be fundamental to evolution and the likelihood of acquiring many diseases. This article explores the hypothesis that, for transgenerationally inherited chromatin structures, “genotype predisposes epitype”, and that epitype functions as a modifier of gene expression within the classical central dogma of molecular biology. Evidence for the causal contribution of genotype to inherited epitypes and epigenetic risk comes primarily from two different kinds of studies discussed herein. The first and direct method of research proceeds by the examination of the transgenerational inheritance of epitype and the penetrance of phenotype among genetically related individuals. The second approach identifies epitypes that are duplicated (as DNA sequences are duplicated and evolutionarily conserved among repeated patterns in the DNA sequence. The body of this article summarizes particularly robust examples of these studies from humans, mice, Arabidopsis, and other organisms. The bulk of the data from both areas of research support the hypothesis that genotypes predispose the likelihood of displaying various epitypes, but for only a few classes of epitype. This analysis suggests that renewed efforts are needed in identifying polymorphic DNA sequences that determine variable nucleosome positioning and DNA methylation as the primary cause of inherited epigenome-induced pathologies. By contrast, there is very little evidence that DNA sequence directly

Transgenerational Social Stress, Immune Factors, Hormones, and Social Behavior

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Christopher Anthony Murgatroyd

2016-01-01

Full Text Available A social signal transduction theory of depression has been proposed that states that exposure to social adversity alters the immune response and these changes mediate symptoms of depression such as anhedonia and impairments in social behavior. The exposure of maternal rats to the chronic social stress (CSS of a male intruder depresses maternal care and impairs social behavior in the F1 and F2 offspring of these dams. The objective of the present study was to characterize basal peripheral levels of several immune factors and related hormone levels in the adult F2 offspring of CSS exposed dams and assess whether changes in these factors are associated with previously reported deficits in allogrooming behavior. CSS decreased acid glycoprotein (α1AGP and intercellular adhesion molecule-1 (ICAM-1 in F2 females, and increased granulocyte macrophage-colony stimulating factor (GM-CSF in F2 males. There were also sex dependent changes in IL-18, tissue inhibitors of metalloproteinases 1 (TIMP-1, and vascular endothelial growth factor (VEGF. Progesterone was decreased and alpha melanocyte stimulating hormone (α-MSH was increased in F2 males, and brain-derived neurotrophic factor (BDNF was decreased in F2 females. Changes in α1AGP, GM-CSF, progesterone and α-MSH were correlated with decreased allogrooming in the F2 offspring of stressed dams. These results support the hypothesis that transgenerational social stress affects both the immune system and social behavior, and also support previous studies on the adverse effects of early life stress on immune functioning and stress associated immunological disorders, including the increasing prevalence of asthma. The immune system may represent an important transgenerational etiological factor in disorders which involve social and/or early life stress associated changes in social behavior, such as depression, anxiety, and autism, as well as comorbid immune disorders. Future studies involving immune and

Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma.

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Gapp, Katharina; Bohacek, Johannes; Grossmann, Jonas; Brunner, Andrea M; Manuella, Francesca; Nanni, Paolo; Mansuy, Isabelle M

2016-10-01

Adverse experiences in early life are risk factors for the development of behavioral and physiological symptoms that can lead to psychiatric and cognitive disorders later in life. Some of these symptoms can be transmitted to the offspring, in some cases by non-genomic mechanisms involving germ cells. Using a mouse model of unpredictable maternal separation and maternal stress, we show that postnatal trauma alters coping behaviors in adverse conditions in exposed males when adult and in their adult male progeny. The behavioral changes are accompanied by increased glucocorticoid receptor (GR) expression and decreased DNA methylation of the GR promoter in the hippocampus. DNA methylation is also decreased in sperm cells of exposed males when adult. Transgenerational transmission of behavioral symptoms is prevented by paternal environmental enrichment, an effect associated with the reversal of alterations in GR gene expression and DNA methylation in the hippocampus of the male offspring. These findings highlight the influence of both negative and positive environmental factors on behavior across generations and the plasticity of the epigenome across life.

Errors, uncertainties and other problems associated with the interpretation of transgenerational epidemiological studies with special reference to postulated ionising radiation effects

International Nuclear Information System (INIS)

Slovak, A.J.M.

2000-01-01

The transgenerational effects debate of recent years can, in the light of current knowledge, be seen as a working example of the operation of a powerful range of errors, biases and confounders. These have often helped to obfuscate the issues addressed to the disbenefit of interested parties such as vicinity populations and workforces. The possibility of transgenerational effects has been entertained as a theoretical constant throughout the history of radiation science being given particular direction and focus by the work of Mueller in the 1920's. The absence of such effect in bomb survivors was therefore somewhat surprising to researchers even though this relative radio resistance was confirmed by later animal studies, such as by Russell and Selby. For emotive and situational reasons the renewed transgenerational debate of the last couple of decades has focused largely on childhood leukaemia, a very late, even remote-manifesting putative, transgenerational effect. This effect has now been demonstrated to be mainly due to confounding, most likely by population mixing, even in the sentinel study population of Seascale, near Sellafield. Little attention had been paid to the nature of the biological plausibility of putative transgenerational effects of ionizing radiation in terms of likelihood and closeness of fit. Thus there is a likelihood gradient of expected magnitude of effect which may be predicted to run from early to late manifesting defects. This would be expected to be high for pre-implantation loss and low for stillbirths or childhood cancer. Cited biological concordance also seldom takes regard of dose and dose rate. This is a particular problem because many epidemiological studies use more or less crude surrogate of dose such as monitored/never monitored or mechanical proportionalisation of annual dose summaries to shorter critical periods (such as spermatogenesis). In questionnaire studies, which are often regarded as inescapable in reproductive

Transgenerational inheritance of heart disorders caused by paternal bisphenol A exposure

International Nuclear Information System (INIS)

Lombó, Marta; Fernández-Díez, Cristina; González-Rojo, Silvia; Navarro, Claudia; Robles, Vanesa; Herráez, María Paz

2015-01-01

Bisphenol A (BPA) is an endocrine disruptor used in manufacturing of plastic devices, resulting in an ubiquitous presence in the environment linked to human infertility, obesity or cardiovascular diseases. Both transcriptome and epigenome modifications lie behind these disorders that might be inherited transgenerationally when affecting germline. To assess potential effects of paternal exposure on offspring development, adult zebrafish males were exposed to BPA during spermatogenesis and mated with non-treated females. Results showed an increase in the rate of heart failures of progeny up to the F2, as well as downregulation of 5 genes involved in cardiac development in F1 embryos. Moreover, BPA causes a decrease in F0 and F1 sperm remnant mRNAs related to early development. Results reveal a paternal inheritance of changes in the insulin signaling pathway due to downregulation of insulin receptor β mRNAs, suggesting a link between BPA male exposure and disruption of cardiogenesis in forthcoming generations. - Highlights: • We examine the effects of adult male exposure to BPA on the progeny (F1 and F2). • Paternal exposure promotes similar cardiac malformations to those caused by direct exposure. • BPA applied during spermatogenesis decrease the insra and insrb transcripts in spermatozoa. • Sperm insrb transcript controls embryonic expression being the downregulation inherited by F1. • Paternal BPA exposure impairs heart development in F1 and F2 disrupting insulin signaling pathway. - Paternal bisphenol A exposure impairs cardiac development throughout generations.

[The transgenerational transmission of traumatic experiences of the Second World War over three generations--a psychoanalytical perspective].

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Silke, Wiegand-Grefe; Möller, Birgit

2012-01-01

The paper presents some reflections on the transgenerational transmission of traumatic experiences of war and in particular bombing during Second World War. These theoretical considerations are based on a case study (family interview) deriving from the research project "Kriegskindheit im Hamburger Feuersturm" additionally illustrated and complemented with impressions based on interviews with three generations in context of the project.

Trans-generational responses to low pH depend on parental gender in a calcifying tubeworm.

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Lane, Ackley; Campanati, Camilla; Dupont, Sam; Thiyagarajan, Vengatesen

2015-06-03

The uptake of anthropogenic CO2 emissions by oceans has started decreasing pH and carbonate ion concentrations of seawater, a process called ocean acidification (OA). Occurring over centuries and many generations, evolutionary adaptation and epigenetic transfer will change species responses to OA over time. Trans-generational responses, via genetic selection or trans-generational phenotypic plasticity, differ depending on species and exposure time as well as differences between individuals such as gender. Males and females differ in reproductive investment and egg producing females may have less energy available for OA stress responses. By crossing eggs and sperm from the calcareous tubeworm Hydroides elegans (Haswell, 1883) raised in ambient (8.1) and low (7.8) pH environments, we observed that paternal and maternal low pH experience had opposite and additive effects on offspring. For example, when compared to offspring with both parents from ambient pH, growth rates of offspring of fathers or mothers raised in low pH were higher or lower respectively, but there was no difference when both parents were from low pH. Gender differences may result in different selection pressures for each gender. This may result in overestimates of species tolerance and missed opportunities of potentially insightful comparisons between individuals of the same species.

No evidence for thermal transgenerational plasticity in metabolism when minimizing the potential for confounding effects.

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Kielland, Ø N; Bech, C; Einum, S

2017-01-11

Environmental change may cause phenotypic changes that are inherited across generations through transgenerational plasticity (TGP). If TGP is adaptive, offspring fitness increases with an increasing match between parent and offspring environment. Here we test for adaptive TGP in somatic growth and metabolic rate in response to temperature in the clonal zooplankton Daphnia pulex Animals of the first focal generation experienced thermal transgenerational 'mismatch' (parental and offspring temperatures differed), whereas conditions of the next two generations matched the (grand)maternal thermal conditions. Adjustments of metabolic rate occurred during the lifetime of the first generation (i.e. within-generation plasticity). However, no further change was observed during the subsequent two generations, as would be expected under TGP. Furthermore, we observed no tendency for increased juvenile somatic growth (a trait highly correlated with fitness in Daphnia) over the three generations when reared at new temperatures. These results are inconsistent with existing studies of thermal TGP, and we describe how previous experimental designs may have confounded TGP with within-generation plasticity and selective mortality. We suggest that the current evidence for thermal TGP is weak. To increase our understanding of the ecological and evolutionary role of TGP, future studies should more carefully identify possible confounding factors. © 2017 The Author(s).

A Decade of Exploring the Mammalian Sperm Epigenome: Paternal Epigenetic and Transgenerational Inheritance

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Alexandre Champroux

2018-05-01

Full Text Available The past decade has seen a tremendous increase in interest and progress in the field of sperm epigenetics. Studies have shown that chromatin regulation during male germline development is multiple and complex, and that the spermatozoon possesses a unique epigenome. Its DNA methylation profile, DNA-associated proteins, nucleo-protamine distribution pattern and non-coding RNA set up a unique epigenetic landscape which is delivered, along with its haploid genome, to the oocyte upon fertilization, and therefore can contribute to embryogenesis and to the offspring health. An emerging body of compelling data demonstrates that environmental exposures and paternal lifestyle can change the sperm epigenome and, consequently, may affect both the embryonic developmental program and the health of future generations. This short review will attempt to provide an overview of what is currently known about sperm epigenome and the existence of transgenerational epigenetic inheritance of paternally acquired traits that may contribute to the offspring phenotype.

Transgenerational exposure of North Atlantic bivalves to ocean acidification renders offspring more vulnerable to low pH and additional stressors.

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Griffith, Andrew W; Gobler, Christopher J

2017-09-12

While early life-stage marine bivalves are vulnerable to ocean acidification, effects over successive generations are poorly characterized. The objective of this work was to assess the transgenerational effects of ocean acidification on two species of North Atlantic bivalve shellfish, Mercenaria mercenaria and Argopecten irradians. Adults of both species were subjected to high and low pCO 2 conditions during gametogenesis. Resultant larvae were exposed to low and ambient pH conditions in addition to multiple, additional stressors including thermal stress, food-limitation, and exposure to a harmful alga. There were no indications of transgenerational acclimation to ocean acidification during experiments. Offspring of elevated pCO 2 -treatment adults were significantly more vulnerable to acidification as well as the additional stressors. Our results suggest that clams and scallops are unlikely to acclimate to ocean acidification over short time scales and that as coastal oceans continue to acidify, negative effects on these populations may become compounded and more severe.

[E. M. Jellinek's silenced and silencing transgenerational story].

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Kelemen, Gábor; Márk, Mónika

2013-01-01

Jellinek is a kind of archetypal character for future generations in the field of addiction studies. His implosion in the arena of alcoholism around the age of 50 was an unexpected challenge to medical science. We know very little about his own role models giving an intellectual and moral compass to his pragmatic creativity. More than 30 years has passed since Jellinek's death when an American sociologist Ron Roizen started unearthing his silent story. Roizen discerned that there are a lot of unsaid and muted issues in his personal Hungarian past. Our paper, based on the authors' research in Hungarian archives and other sources reveals that not just Jellinek's personal but his transgenerational narrative has been not-yet-said. This silenced and silencing history appears an unfinished business of acculturation of the family, which started prior to four generations. Authors have been concluding that the issue of religious conversion is a critical point in the process of acculturation. They examine the counter move of loyalty to family values and driving force of assimilation making their story unspeakable.

Trans-generational Immune Priming Protects the Eggs Only against Gram-Positive Bacteria in the Mealworm Beetle.

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Aurore Dubuffet

2015-10-01

Full Text Available In many vertebrates and invertebrates, offspring whose mothers have been exposed to pathogens can exhibit increased levels of immune activity and/or increased survival to infection. Such phenomena, called "Trans-generational immune priming" (TGIP are expected to provide immune protection to the offspring. As the offspring and their mother may share the same environment, and consequently similar microbial threats, we expect the immune molecules present in the progeny to be specific to the microbes that immune challenged the mother. We provide evidence in the mealworm beetle Tenebrio molitor that the antimicrobial activity found in the eggs is only active against Gram-positive bacteria, even when females were exposed to Gram-negative bacteria or fungi. Fungi were weak inducers of TGIP while we obtained similar levels of anti-Gram-positive activity using different bacteria for the maternal challenge. Furthermore, we have identified an antibacterial peptide from the defensin family, the tenecin 1, which spectrum of activity is exclusively directed toward Gram-positive bacteria as potential contributor to this antimicrobial activity. We conclude that maternal transfer of antimicrobial activity in the eggs of T. molitor might have evolved from persistent Gram-positive bacterial pathogens between insect generations.

Nicotine during pregnancy: changes induced in neurotransmission, which could heighten proclivity to addict and induce maladaptive control of attention.

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Kohlmeier, K A

2015-06-01

Prenatal exposure to nicotine, occurring either via maternal smoking or via use of transdermal nicotine patches to facilitate cigarette abstinence by pregnant women, is associated with ∼ 13% of pregnancies worldwide. Nicotine exposure during gestation has been correlated with several negative physiological and psychosocial outcomes, including heightened risk for aberrant behaviors involving alterations in processing of attention as well as an enhanced liability for development of drug dependency. Nicotine is a terotogen, altering neuronal development of various neurotransmitter systems, and it is likely these alterations participate in postnatal deficits in attention control and facilitate development of drug addiction. This review discusses the alterations in neuronal development within the brain's major neurotransmitter systems, with special emphasis placed on alterations within the laterodorsal tegmental nucleus, in light of the role this cholinergic nucleus plays in attention and addiction. Changes induced within this nucleus by gestational exposure to nicotine, in combination with changes induced in other brain regions, are likely to contribute to the transgenerational burden imposed by nicotine. Although neuroplastic changes induced by nicotine are not likely to act in isolation, and are expected to interact with epigenetic changes induced by preconception exposure to drugs of abuse, unraveling these changes within the developing brain will facilitate eventual development of targeted treatments for the unique vulnerability for arousal disorders and development of addiction within the population of individuals who have been prenatally exposed to nicotine.

Transgenerational epigenetic effects on animal behaviour.

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Jensen, Per

2013-12-01

Over the last decade a shift in paradigm has occurred with respect to the interaction between environment and genes. It is now clear that animal genomes are regulated to a large extent as a result of input from environmental events and experiences, which cause short- and long-term modifications in epigenetic markings of DNA and histones. In this review, the evidence that such epigenetic modifications can affect the behaviour of animals is explored, and whether such acquired behaviour alterations can transfer across generation borders. First, the mechanisms by which experiences cause epigenetic modifications are examined. This includes, for example, methylation of cytosine in CpG positions and acetylation of histones, and studies showing that this can be modified by early experiences. Secondly, the evidence that specific modifications in the epigenome can be the cause of behaviour variation is reviewed. Thirdly, the extent to which this phenotypically active epigenetic variants can be inherited either through the germline or through reoccurring environmental conditions is examined. A particularly interesting observation is that epigenetic modifications are often linked to stress, and may possibly be mediated by steroid effects. Finally, the idea that transgenerationally stable epigenetic variants may serve as substrates for natural selection is explored, and it is speculated that they may even predispose for directed, non-random mutations. Copyright © 2013 Elsevier Ltd. All rights reserved.

Trans-generational maternal effect: temperature influences egg size of the offspring in Atlantic salmon Salmo salar.

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Jonsson, B; Jonsson, N

2016-08-01

Effect of increased temperature during egg maturation on the mass of single eggs produced by the offspring was investigated experimentally in Atlantic salmon Salmo salar. Mass of eggs produced by next-generation females was larger when their mothers experienced warmer water during the last two months of egg maturation, relative to those that experienced unheated river water. There was no similar trans-generational paternal effect on offspring egg mass. © 2016 The Fisheries Society of the British Isles.

Contrasting gene expression programs correspond with predator-induced phenotypic plasticity within and across generations in Daphnia.

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Hales, Nicole R; Schield, Drew R; Andrew, Audra L; Card, Daren C; Walsh, Matthew R; Castoe, Todd A

2017-10-01

Research has shown that a change in environmental conditions can alter the expression of traits during development (i.e., "within-generation phenotypic plasticity") as well as induce heritable phenotypic responses that persist for multiple generations (i.e., "transgenerational plasticity", TGP). It has long been assumed that shifts in gene expression are tightly linked to observed trait responses at the phenotypic level. Yet, the manner in which organisms couple within- and TGP at the molecular level is unclear. Here we tested the influence of fish predator chemical cues on patterns of gene expression within- and across generations using a clone of Daphnia ambigua that is known to exhibit strong TGP but weak within-generation plasticity. Daphnia were reared in the presence of predator cues in generation 1, and shifts in gene expression were tracked across two additional asexual experimental generations that lacked exposure to predator cues. Initial exposure to predator cues in generation 1 was linked to ~50 responsive genes, but such shifts were 3-4× larger in later generations. Differentially expressed genes included those involved in reproduction, exoskeleton structure and digestion; major shifts in expression of genes encoding ribosomal proteins were also identified. Furthermore, shifts within the first-generation and transgenerational shifts in gene expression were largely distinct in terms of the genes that were differentially expressed. Such results argue that the gene expression programmes involved in within- vs. transgeneration plasticity are fundamentally different. Our study provides new key insights into the plasticity of gene expression and how it relates to phenotypic plasticity in nature. © 2017 John Wiley & Sons Ltd.

Extended evolutionary psychology: the importance of transgenerational developmental plasticity

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Karola eStotz

2014-08-01

Full Text Available What kind mechanisms one deems central for the evolutionary process deeply influences one’s understanding of the nature of organisms, including cognition. Reversely, adopting a certain approach to the nature of life and cognition and the relationship between them or between the organism and its environment should affect one’s view of evolutionary theory. This paper explores this reciprocal relationship in more detail. In particular it argues that the view of living and cognitive systems, especially humans, as deeply integrated beings embedded in and transformed by their genetic, epigenetic (molecular and cellular, behavioral, ecological, socio-cultural and cognitive-symbolic legacies calls for an extended evolutionary synthesis that goes beyond either a theory of genes juxtaposed against a theory of cultural evolution and or even more sophisticated theories of gene-culture coevolution and niche construction. Environments, particularly in the form of developmental environments, do not just select for variation, they also create new variation by influencing development through the reliable transmission of non-genetic but heritable information. This paper stresses particularly views of embodied, embedded, enacted and extended cognition, and their relationship to those aspects of extended inheritance that lie between genetic and cultural inheritance, the still grey area of epigenetic and behavioral inheritance systems that play a role in parental effect. These are the processes that can be regarded as transgenerational developmental plasticity and that I think can most fruitfully contribute to, and be investigated by, developmental psychology.

Extended evolutionary psychology: the importance of transgenerational developmental plasticity.

Science.gov (United States)

Stotz, Karola

2014-01-01

What kind mechanisms one deems central for the evolutionary process deeply influences one's understanding of the nature of organisms, including cognition. Reversely, adopting a certain approach to the nature of life and cognition and the relationship between them or between the organism and its environment should affect one's view of evolutionary theory. This paper explores this reciprocal relationship in more detail. In particular it argues that the view of living and cognitive systems, especially humans, as deeply integrated beings embedded in and transformed by their genetic, epigenetic (molecular and cellular), behavioral, ecological, socio-cultural and cognitive-symbolic legacies calls for an extended evolutionary synthesis that goes beyond either a theory of genes juxtaposed against a theory of cultural evolution and or even more sophisticated theories of gene-culture coevolution and niche construction. Environments, particularly in the form of developmental environments, do not just select for variation, they also create new variation by influencing development through the reliable transmission of non-genetic but heritable information. This paper stresses particularly views of embodied, embedded, enacted and extended cognition, and their relationship to those aspects of extended inheritance that lie between genetic and cultural inheritance, the still gray area of epigenetic and behavioral inheritance systems that play a role in parental effect. These are the processes that can be regarded as transgenerational developmental plasticity and that I think can most fruitfully contribute to, and be investigated by, developmental psychology.

Politics, doctors, assisted reproductive technologies & religion: Transgenerational understandings and experiences of single motherhood in Spain.

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Bravo-Moreno, Ana

2017-10-01

The aim is to achieve a transgenerational view of single motherhood in Spain, to look at which contexts it arises in, how it changes with the introduction of assisted reproduction, and how the role of religion in Spanish society permeates medical practice and affects the lives of women patients. I examine single motherhood and investigate two interconnected themes: (a) being a mother and being mothered are both permeated with sociocultural, political, religious, economic and psychological significance; (b) Spain led Europe in multiple births due to assisted reproduction, thus ethical conflicts and patient rights are analyzed.

Next-generation systemic acquired resistance.

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Luna, Estrella; Bruce, Toby J A; Roberts, Michael R; Flors, Victor; Ton, Jurriaan

2012-02-01

Systemic acquired resistance (SAR) is a plant immune response to pathogen attack. Recent evidence suggests that plant immunity involves regulation by chromatin remodeling and DNA methylation. We investigated whether SAR can be inherited epigenetically following disease pressure by Pseudomonas syringae pv tomato DC3000 (PstDC3000). Compared to progeny from control-treated Arabidopsis (Arabidopsis thaliana; C(1)), progeny from PstDC3000-inoculated Arabidopsis (P(1)) were primed to activate salicylic acid (SA)-inducible defense genes and were more resistant to the (hemi)biotrophic pathogens Hyaloperonospora arabidopsidis and PstDC3000. This transgenerational SAR was sustained over one stress-free generation, indicating an epigenetic basis of the phenomenon. Furthermore, P(1) progeny displayed reduced responsiveness of jasmonic acid (JA)-inducible genes and enhanced susceptibility to the necrotrophic fungus Alternaria brassicicola. This shift in SA- and JA-dependent gene responsiveness was not associated with changes in corresponding hormone levels. Instead, chromatin immunoprecipitation analyses revealed that SA-inducible promoters of PATHOGENESIS-RELATED GENE1, WRKY6, and WRKY53 in P(1) plants are enriched with acetylated histone H3 at lysine 9, a chromatin mark associated with a permissive state of transcription. Conversely, the JA-inducible promoter of PLANT DEFENSIN1.2 showed increased H3 triple methylation at lysine 27, a mark related to repressed gene transcription. P(1) progeny from the defense regulatory mutant non expressor of PR1 (npr1)-1 failed to develop transgenerational defense phenotypes, demonstrating a critical role for NPR1 in expression of transgenerational SAR. Furthermore, the drm1drm2cmt3 mutant that is affected in non-CpG DNA methylation mimicked the transgenerational SAR phenotype. Since PstDC3000 induces DNA hypomethylation in Arabidopsis, our results suggest that transgenerational SAR is transmitted by hypomethylated genes that direct priming

Evidence of constitutional MLH1 epimutation associated to transgenerational inheritance of cancer susceptibility.

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Crépin, Michel; Dieu, Marie-Claire; Lejeune, Sophie; Escande, Fabienne; Boidin, Denis; Porchet, Nicole; Morin, Gilles; Manouvrier, Sylvie; Mathieu, Michèle; Buisine, Marie-Pierre

2012-01-01

Constitutional epimutations of DNA mismatch repair (MMR) genes have been recently reported as a possible cause of Lynch syndrome. However, little is known about their prevalence, the risk of transmission through the germline and the risk for carriers to develop cancers. In this study, we evaluated the contribution of constitutional epimutations of MMR genes in Lynch syndrome. A cohort of 134 unrelated Lynch syndrome-suspected patients without MMR germline mutation was screened for constitutional epimutations of MLH1 and MSH2 by quantitative bisulfite pyrosequencing. Patients were also screened for the presence of EPCAM deletions, a possible cause of MSH2 methylation. Tumors from patients with constitutional epimutations were extensively analyzed. We identified a constitutional MLH1 epimutation in two proband patients. For one of them, we report for the first time evidence of transmission to two children who also developed early colonic tumors, indicating that constitutional MLH1 epimutations are associated to a real risk of transgenerational inheritance of cancer susceptibility. Moreover, a somatic BRAF mutation was detected in one affected child, indicating that tumors from patients carrying constitutional MLH1 epimutation can mimic MSI-high sporadic tumors. These findings may have important implications for future diagnostic strategies and genetic counseling. © 2011 Wiley Periodicals, Inc.

Ionising radiation and trans-generational instability

International Nuclear Information System (INIS)

Vrhovac, I.; Niksic, G.

2007-01-01

Indirect monitoring of the impact posed by ionising radiation to the genome instability of the descendants, consequent to the irradiation of one of their parents, boils down to the investigation of changes occurring exclusively in the mini-satellite loci of the cells constituting the gametal developmental line. The resultant mini-satellite mutations are expressed in their percentages, and equal to the ratio of the number of mutated alleles in that particular generation over the total number of alleles present. The impact of ionising radiation to the irradiated parent's offspring was first noticed on haematopoietic mouse stem-cells. Even though an irradiated cell of a female parent lacks any mutations whatsoever, daughter cells present with the increased mutation rates. The observed phenomenon of the so called trans-generational instability has been defined as the occurrence of mutations in the genome of individuals originating from the irradiated ancestors. Due to the aforementioned, one can conclude that these mutations need not be present in the irradiated parental cells, and do not necessarily vanish in the next few generations, but may result in the increase in mutation rates observed in the latter. The results of the investigations performed on the animal model, as well as of those carried out in human population, point to the occurrence of significant changes to be found on mini-satellite loci of the descending generation, while the mechanism underlying those changes hasn't been completely clarified yet, and, therefore, calls for the further investigation. (author)

Assessing triclosan-induced ecological and trans-generational effects in natural phytoplankton communities: a trait-based field method.

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Pomati, Francesco; Nizzetto, Luca

2013-07-01

We exposed replicated phytoplankton communities confined in semi-permeable membrane-based mesocosms to 0, 0.1, 1 and 10 μg L(-1) triclosan (TCS) and placed them back in their original environment to investigate the occurrence of trans-generational responses at individual, population and community levels. TCS diffused out of mesocosms with a half-life of less than 8 h, so that only the parental generation was directly stressed. At the beginning of the experiment and after 7 days (approximately 2 generations) we analysed responses in the phytoplankton using scanning flow-cytometry. We acquired information on several individually expressed phenotypic traits, such as size, biovolume, pigment fluorescence and packaging, for thousands of individuals per replicated population and derived population and community aggregated traits. We found significant changes in community functioning (increased productivity in terms of biovolume and total fluorescence), with maximal effects at 1 μg L(-1) TCS. We detected significant and dose-dependent responses on population traits, such as changes in abundance for several populations, increased average size and fluorescence of cells, and strong changes in within-population trait mean and variance (suggesting micro-evolutionary effects). We applied the Price equation approach to partition community effects (changes in biovolume or fluorescence) in their physiological and ecological components, and quantified the residual component (including also evolutionary responses). Our results suggested that evolutionary or inheritable phenotypic plasticity responses may represent a significant component of the total observed change following exposure and over relatively small temporal scales.

Trans-generational effects of mild heat stress on the life history traits of an aphid parasitoid.

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Ismaeil, Ibrahim; Doury, Géraldine; Desouhant, Emmanuel; Dubois, Françoise; Prevost, Geneviève; Couty, Aude

2013-01-01

Temperature changes are common in nature and insects are particularly exposed and sensitive to such variations which can be potential stresses, ultimately affecting life history traits and overall fitness. Braconids have been widely used to study the effects of temperature on host-parasitoid interactions and the present work focused on the solitary endoparasitoid Aphidius ervi Haliday (Hymenoptera: Braconidae Aphidiidae), an efficient biological control agent commercially used against aphids such as the potato aphid Macrosiphum euphorbiae Thomas (Sternorrhyncha: Aphididae). Contrary to previous studies using heat shocks at extreme temperatures, we evaluated the effects of mild heat stresses by transferring young parasitoid adults from the constant temperature of 20°C to either a warm (25°C) or hot (28°C) temperature, for either 1 h or 48 h. Such treatments are consistent with situations commonly experienced by parasitoids when moved from their rearing conditions to greenhouses or field conditions. The effects were evaluated both on the heat stressed A. ervi adults (G0) (immediate effects) and on their first generation (G1) progeny (trans-generational effects). G0 wasps' mortality was significantly affected by the temperature in interaction with the duration of the stress. Longevity of G0 wasps surviving the heat stress was negatively affected by the temperature and females lived longer than males. Heat stress applied to A. ervi parents also had consequences on their G1 progeny whose developmental time, rates of mummification and percentage of parasitoid completing total development were negatively affected. Surprisingly, the egg load at emergence of the G1 female progeny was increased when their mothers had been submitted to a mild heat stress of 25°C or 28°C. These results clearly demonstrate trans-generational phenotypic plasticity, showing that adaptation to thermal stresses may be achieved via maternal effects. This study also sheds light on the complexity

Why is parental lifespan linked to children's chances of reaching a high age? A transgenerational hypothesis.

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Vågerö, Denny; Aronsson, Vanda; Modin, Bitte

2018-04-01

Transgenerational determinants of longevity are poorly understood. We used data from four linked generations (G0, G1, G2 and G3) of the Uppsala Birth Cohort Multigeneration Study to address this issue. Mortality in G1 (N = 9565) was followed from 1961-2015 and analysed in relation to tertiles of their parents' (G0) age-at-death using Cox regression. Parental social class and marital status were adjusted for in the analyses, as was G1's birth order and adult social class. For an almost entirely deceased segment of G1 (n = 1149), born 1915-1917, we compared exact age-at-death with G0 parents' age-at-death. Finally, we explored 'resilience' as a potentially important mechanism for intergenerational transmission of longevity, using conscript information from psychological interviews of G2 and G3 men. G0 men's and women's ages-at-death were independently associated with G1 midlife and old age mortality. This association was robust and minimally reduced when G0 and G1 social class were adjusted for. We observed an increased lifespan in all social groups. Median difference in age-at-death for sons compared to fathers was + 3.9 years, and + 6.9 years for daughters compared to mothers.Parents' and maternal grandmother's longevity were associated with resilience in subsequent generations. Resilience scores of G2 men were also associated with those of their G3 sons and with their own mortality in midlife. The chance of reaching a high age is transmitted from parents to children in a modest, but robust way. Longevity inheritance is paralleled by the inheritance of individual resilience. Individual resilience, we propose, develops in the first part of life as a response to adversity and early experience in general. This gives rise to a transgenerational pathway, distinct from social class trajectories. A theory of longevity inheritance should bring together previous thinking around general susceptibility, frailty and resilience with new insights from epigenetics and social

Trans-generational effects of mild heat stress on the life history traits of an aphid parasitoid.

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Ibrahim Ismaeil

Full Text Available Temperature changes are common in nature and insects are particularly exposed and sensitive to such variations which can be potential stresses, ultimately affecting life history traits and overall fitness. Braconids have been widely used to study the effects of temperature on host-parasitoid interactions and the present work focused on the solitary endoparasitoid Aphidius ervi Haliday (Hymenoptera: Braconidae Aphidiidae, an efficient biological control agent commercially used against aphids such as the potato aphid Macrosiphum euphorbiae Thomas (Sternorrhyncha: Aphididae. Contrary to previous studies using heat shocks at extreme temperatures, we evaluated the effects of mild heat stresses by transferring young parasitoid adults from the constant temperature of 20°C to either a warm (25°C or hot (28°C temperature, for either 1 h or 48 h. Such treatments are consistent with situations commonly experienced by parasitoids when moved from their rearing conditions to greenhouses or field conditions. The effects were evaluated both on the heat stressed A. ervi adults (G0 (immediate effects and on their first generation (G1 progeny (trans-generational effects. G0 wasps' mortality was significantly affected by the temperature in interaction with the duration of the stress. Longevity of G0 wasps surviving the heat stress was negatively affected by the temperature and females lived longer than males. Heat stress applied to A. ervi parents also had consequences on their G1 progeny whose developmental time, rates of mummification and percentage of parasitoid completing total development were negatively affected. Surprisingly, the egg load at emergence of the G1 female progeny was increased when their mothers had been submitted to a mild heat stress of 25°C or 28°C. These results clearly demonstrate trans-generational phenotypic plasticity, showing that adaptation to thermal stresses may be achieved via maternal effects. This study also sheds light on

Transgenerational hormonal imprinting caused by vitamin A and vitamin D treatment of newborn rats. Alterations in the biogenic amine contents of the adult brain.

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Tekes, Kornélia; Gyenge, Melinda; Hantos, Mónika; Csaba, György

2009-10-01

Biogenic amines (norepinephrine, dopamine, homovanillic acid, serotonin and 5-hyroxyindole acetic acid) were measured by HPLC method in adult F1 generation rats' brain regions (brainstem, hypothalamus, hippocampus, striatum and frontal cortex), whose mothers (P generation) were treated with vitamin A or vitamin D neonatally (hormonal imprinting). Many significant differences were found, related to the maternally untreated controls. In the earlier studied P generation females, vitamin A consistently influenced the serotonerg system (5HIAA), while vitamin D the dopaminerg system (DA or HVA). Vitamin A imprinting always resulted in reduced, while that by vitamin D always in increased tissue levels. In the present case (directly untreated F1 generation) the transgenerational effect was not unidirectional, however biogenic amine tissue levels were strongly disturbed and brain-area dependent. The results call attention to the transgenerational effect of hormonal imprinting in the case of receptor level acting vitamins which are frequently used in the most imprinting-sensitive period (perinatally) of human life and suggests that caution is warranted.

[Revival of transgenerational traumas (TGT) in psychotherapeutic context. Some possibilities of interpretation in four cases].

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Vas, Pál József; Zseni, Annamária

2007-01-01

The authors think that the destructive factors that influence one's destiny in life could be the transmissions of collective, familial, and other factors coming from the clan system. This transmission is described by the concept of transgenerational trauma. A burdensome heritage can either directly, or indirectly, be passed on, even through several generations, as it can be seen in the presented cases. Also cases of intrauterine catastrophes are presented. A catastrophe like this is the case of vanishing twins. Four psychotherapy cases are analyzed in which the patients' sufferings may be attributed to the intrauterine death of their twin. In two of the cases the loss of a twin sibling is a proven biological fact. In the other two cases there is a high probability that the same has happened. A novel element introduced by the authors in the interpretation of this phenomenon is the concept that the fetus and the embrio may be able to preserve the memories of the experienced catastrophes, which as state-dependent memories will be revived in stress situations in the form of physical symptoms and feelings connected to the trauma. However, at this point in time traditional medical thinking is unable to explain the process through which a burdensome heritage is taken over from previous generations. The authors present Bert Hellinger's family constellation and Rupert Sheldrake's theory of morphic resonance as well as the uncertainty principle of quantum psychology. All these consider the multi-dimensional, topological reality that is beyond time and not the four-dimensional geometrical space as the medium in which transgenerational pieces of information spread.

Plasticity to salinity and transgenerational effects in the nonnative shrub Baccharis halimifolia: Insights into an estuarine invasion.

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Caño, Lidia; Fuertes-Mendizabal, Teresa; García-Baquero, Gonzalo; Herrera, Mercedes; González-Moro, M Begoña

2016-05-01

Abiotic constraints act as selection filters for plant invasion in stressful habitats. Adaptive phenotypic plasticity and transgenerational effects play a major role in colonization of heterogeneous habitats when the scale of environmental variation is smaller than that of gene flow. We investigated how plasticity and parental salinity conditions influence the performance of the invasive dioecious shrub Baccharis halimifolia, which replaces heterogeneous estuarine communities in Europe with monospecific and continuous stands. In two greenhouse experiments, we grew plants derived from seeds and cuttings collected through interspersed patches differing in edaphic salinity from an invasive population. We estimated parental environmental salinity from leaf Na(+) content in parental plants, and we measured fitness and ion homeostasis of the offspring grown in contrasting salinity conditions. Baccharis halimifolia tolerates high salinity but experiences drastic biomass reduction at moderate salinity. At moderate salinity, responses to salinity are affected by the parental salinity: flowering initiation in seedlings and male cuttings is positively correlated with parental leaf Na(+) content, and biomass is positively correlated with maternal leaf Na(+) in female cuttings and seedlings. Plant height, leaf production, specific leaf area, and ionic homeostasis at the low part of the gradient are also affected by parental salinity, suggesting enhanced shoot growth as parental salinity increases. Our results support plasticity to salinity and transgenerational effects as factors with great potential to contribute to the invasive ability of B. halimifolia through estuarine communities of high conservation value. © 2016 Botanical Society of America.

The secret language of destiny: stress imprinting and transgenerational origins of disease

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Zucchi, Fabiola C. R.; Yao, Youli; Metz, Gerlinde A.

2012-01-01

Epigenetic regulation modulates gene expression without altering the DNA sequence to facilitate rapid adjustments to dynamically changing environmental conditions. The formation of an epigenetic memory allows passing on this information to subsequent generations. Here we propose that epigenetic memories formed by adverse environmental conditions and stress represent a critical determinant of health and disease in the F3 generation and beyond. Transgenerational programming of epigenetic regulation may represent a key to understand adult-onset complex disease pathogenesis and cumulative effects of life span and familial disease etiology. Ultimately, the mechanisms of generating an epigenetic memory may become of potentially promising diagnostic and therapeutic relevance due to their reversible nature. Exploring the role of environmental factors, such as stress, in causing variations in epigenetic profiles may lead to new avenues of personalized, preventive medicine based on epigenetic signatures and interventions. PMID:22675331

A genome-wide survey of transgenerational genetic effects in autism.

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Kathryn M Tsang

Full Text Available Effects of parental genotype or parent-offspring genetic interaction are well established in model organisms for a variety of traits. However, these transgenerational genetic models are rarely studied in humans. We have utilized an autism case-control study with 735 mother-child pairs to perform genome-wide screening for maternal genetic effects and maternal-offspring genetic interaction. We used simple models of single locus parent-child interaction and identified suggestive results (P<10(-4 that cannot be explained by main effects, but no genome-wide significant signals. Some of these maternal and maternal-child associations were in or adjacent to autism candidate genes including: PCDH9, FOXP1, GABRB3, NRXN1, RELN, MACROD2, FHIT, RORA, CNTN4, CNTNAP2, FAM135B, LAMA1, NFIA, NLGN4X, RAPGEF4, and SDK1. We attempted validation of potential autism association under maternal-specific models using maternal-paternal comparison in family-based GWAS datasets. Our results suggest that further study of parental genetic effects and parent-child interaction in autism is warranted.

The transgenerational effects of heat stress in the nematode Caenorhabditis remanei are negative and rapidly eliminated under direct selection for increased stress resistance in larvae.

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Sikkink, Kristin L; Ituarte, Catherine M; Reynolds, Rose M; Cresko, William A; Phillips, Patrick C

2014-12-01

Parents encountering stress environments can influence the phenotype of their offspring in a form of transgenerational phenotypic plasticity that has the potential to be adaptive if offspring are thereby better able to deal with future stressors. Here, we test for the existence of anticipatory parental effects in the heat stress response in the highly polymorphic nematode Caenorhabditis remanei. Rather providing an anticipatory response, parents subject to a prior heat stress actually produce offspring that are less able to survive a severe heat shock. Selection on heat shock resistance within the larvae via experimental evolution leads to a loss of sensitivity (robustness) to environmental variation during both the parental and larval periods. Whole genome transcriptional analysis of both ancestor and selected lines shows that there is weak correspondence between genetic pathways induced via temperature shifts during parental and larval periods. Parental effects can evolve very rapidly via selection acting directly on offspring. Copyright © 2014 Elsevier Inc. All rights reserved.

Vinclozolin Exposure in Utero Induces Postpubertal Prostatitis and Reduces Sperm Production via a Reversible Hormone-Regulated Mechanism

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Cowin, Prue A.; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K.; Foster, Paul M. D.; Scott, Hamish S.; Risbridger, Gail P.

2010-01-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-κB activat...

Trans-generational inheritance of herbivory-induced phenotypic changes in Brassica rapa

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Biotic stress can induce plastic changes in fitness-relevant plant traits. Recently, it has been shown that such changes can be transmitted to subsequent generations. However, the occurrence and extent of transmission across different types of traits is still unexplored. Here, we assessed the emerge...

Transgenerational plasticity in the sea: context-dependent maternal effects across the life history.

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Marshall, Dustin J

2008-02-01

Maternal effects can have dramatic influences on the phenotype of offspring. Maternal effects can act as a conduit by which the maternal environment negatively affects offspring fitness, but they can also buffer offspring from environmental change by altering the phenotype of offspring according to local environmental conditions and as such, are a form of transgenerational plasticity. The benefits of maternal effects can be highly context dependent, increasing performance in one life-history stage but reducing it in another. While maternal effects are increasingly well understood in terrestrial systems, studies in the marine environment are typically restricted to a single, early life-history stage. Here, I examine the role of maternal effects across the life history of the bryozoan Bugula neritina. I exposed maternal colonies to a common pollution stress (copper) in the laboratory and then placed them in the field for one week to brood offspring. I then examined the resistance of offspring to copper from toxicant-exposed and toxicant-naïve mothers and found that offspring from toxicant-exposed mothers were larger, more dispersive, and more resistant to copper stress than offspring from naïve mothers. However, maternal exposure history had pervasive, negative effects on the post-metamorphic performance (particularly survival) of offspring: offspring from toxicant-exposed mothers had poorer performance after six weeks in the field, especially when facing high levels of intraspecific competition. Maternal experience can have complex effects on offspring phenotype, enhancing performance in one life-history stage while decreasing performance in another. The context-dependent costs and benefits associated with maternally derived pollution resistance may account for why such resistance is induced rather than continually expressed: mothers must balance the benefits of producing pollution-resistant larvae with the costs of producing poorer performing adults (in the

Gestational Exposure to Sidestream (Secondhand) Cigarette Smoke Promotes Transgenerational Epigenetic Transmission of Exacerbated Allergic Asthma and Bronchopulmonary Dysplasia.

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Singh, Shashi P; Chand, Hitendra S; Langley, Raymond J; Mishra, Neerad; Barrett, Ted; Rudolph, Karin; Tellez, Carmen; Filipczak, Piotr T; Belinsky, Steve; Saeed, Ali I; Sheybani, Aryaz; Exil, Vernat; Agarwal, Hemant; Sidhaye, Venkataramana K; Sussan, Thomas; Biswal, Shyam; Sopori, Mohan

2017-05-15

Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice. Recently, perinatal nicotine injections in rats were reported to induce peroxisome proliferator-activated receptor γ-dependent transgenerational transmission of asthma. Herein, we show that first generation and second generation progeny from gestationally SS-exposed mice exhibit exacerbated AA and BPD that is not dependent on the decrease in peroxisome proliferator-activated receptor γ levels. Lungs from these mice show strong eosinophilic infiltration, excessive Th2 polarization, marked airway hyperresponsiveness, alveolar simplification, decreased lung compliance, and decreased lung angiogenesis. At the molecular level, these changes are associated with increased RUNX3 expression, alveolar cell apoptosis, and the antiangiogenic factor GAX, and decreased expression of HIF-1α and proangiogenic factors NF-κB and VEGFR2 in the 7-d first generation and second generation lungs. Moreover, the lungs from these mice exhibit lower levels of microRNA (miR)-130a and increased levels of miR-16 and miR-221. These miRs regulate HIF-1α-regulated apoptotic, angiogenic, and immune pathways. Thus the intergenerational effects of gestational SS involve epigenetic regulation of HIF-1α through specific miRs contributing to increased incidence of AA and BPD in the progenies. Copyright © 2017 by The American Association of Immunologists, Inc.

Transcriptomics reveal transgenerational effects in purple sea urchin embryos: Adult acclimation to upwelling conditions alters the response of their progeny to differential pCO2 levels.

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Wong, Juliet M; Johnson, Kevin M; Kelly, Morgan W; Hofmann, Gretchen E

2018-03-01

Understanding the mechanisms with which organisms can respond to a rapidly changing ocean is an important research priority in marine sciences, especially in the light of recent predictions regarding the pace of ocean change in the coming decades. Transgenerational effects, in which the experience of the parental generation can shape the phenotype of their offspring, may serve as such a mechanism. In this study, adult purple sea urchins, Strongylocentrotus purpuratus, were conditioned to regionally and ecologically relevant pCO 2 levels and temperatures representative of upwelling (colder temperature and high pCO 2 ) and nonupwelling (average temperature and low pCO 2 ) conditions typical of coastal upwelling regions in the California Current System. Following 4.5 months of conditioning, adults were spawned and offspring were raised under either high or low pCO 2 levels, to examine the role of maternal effects. Using RNA-seq and comparative transcriptomics, our results indicate that differential conditioning of the adults had an effect on the gene expression patterns of the progeny during the gastrula stage of early development. For example, maternal conditioning under upwelling conditions intensified the transcriptomic response of the progeny when they were raised under high versus low pCO 2 conditions. Additionally, mothers that experienced upwelling conditions produced larger progeny. The overall findings of this study are complex, but do suggest that transgenerational plasticity in situ could act as an important mechanism by which populations might keep pace with rapid environmental change. © 2018 John Wiley & Sons Ltd.

Trans-generational desensitization and within-generational resensitization of a sucrose-best neuron in the polyphagous herbivore Helicoverpa armigera (Lepidoptera: Noctuidae).

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Ma, Ying; Li, Jingjing; Tang, Qingbo; Zhang, Xuening; Zhao, Xincheng; Yan, Fengming; van Loon, Joop J A

2016-12-14

Dietary exposure of insects to a feeding deterrent substance for hours to days can induce habituation and concomitant desensitization of the response of peripheral gustatory neurons to such a substance. In the present study, larvae of the herbivore Helicoverpa armigera were fed on diets containing either a high, medium or low concentration of sucrose, a major feeding stimulant. The responsiveness of the sucrose-best neuron in the lateral sensilla styloconica on the galea was quantified. Results showed the response of the sucrose-best neuron exposed to high-sucrose diets decreased gradually over successive generations, resulting in complete desensitization in the 5 th and subsequent generations. However, the sensitivity was completely restored in the ninth generation after neonate larvae were exposed to low-sucrose diet. These findings demonstrate phenotypic plasticity and exclude inadvertent artificial selection for low sensitivity to sucrose. No significant changes were found in the sensitivity of caterpillars which experienced low- or medium-sucrose diets over the same generations. Such desensitization versus re-sensitization did not generalise to the phagosimulant myo-inositol-sensitive neuron or the feeding deterrent-sensitive neuron. Our results demonstrate that under conditions of high sucrose availability trans-generational desensitization of a neuron sensitive to this feeding stimulant becomes more pronounced whereas re-sensitization occurs within one generation.

Reproductive and transgenerational toxicities of phenanthrene on female marine medaka (Oryzias melastigma).

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Sun, Lingbin; Zuo, Zhenghong; Chen, Meng; Chen, Yixin; Wang, Chonggang

2015-05-01

Phenanthrene (PHE) is one of the most abundant polycyclic aromatic hydrocarbons in the aquatic environment and often results from oil spills. To assess the effects of PHE on fish, marine medaka (Oryzias melastigma) was exposed to PHE at 0.06, 0.6, 6 and 60 μg/L. The reproductive functions and transgenerational effects were investigated. After 80 days exposure, the percentage of previtellogenic and vitellogenic oocytes in the ovary showed a significant decrease in the 0.06 and 60 μg/L groups. The mRNA levels of salmon-type gonadotropin releasing hormone, the follicle-stimulating hormone FSHβ, and the luteinizing hormone LHβ in the brain; the cytochrome P450 aromatase gene CYP19A and the estrogen receptor α (ERα) in the ovary; and ERα and vitellogenin VTG1 and 2 in the liver all exhibited significant down-regulation in the 0.06 and 60 μg/L groups, but did not significantly change in the 6 μg/L group compared to the control, which was quite consistent with development of the oocytes. A significant elevation of PHE accumulation in the brain in the 0.06 and 60 μg/L groups gave a reasonable explanation for the nonmonotonic dose-response and also elucidated the action pathway via the brain-pituitary-gonadal axis. The reduction of the time to hatch and the increased cardiac rhythm of embryos were in accord with the PHE accumulative levels in the eggs. The results demonstrated that exposure to PHE at both low and high concentrations can inhibit ovary development. In addition, PHE can be maternally transferred to embryos and influence the health and sustainability of the next generation. Copyright © 2015 Elsevier B.V. All rights reserved.

Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells.

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Babica, Pavel; Zurabian, Rimma; Kumar, Esha R; Chopra, Rajus; Mianecki, Maxwell J; Park, Joon-Suk; Jaša, Libor; Trosko, James E; Upham, Brad L

2016-09-01

Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC50 values for GJIC inhibition being 10 µM for MXC and 126 µM for VIN. MXC inhibited GJIC for at least 24 h, while VIN effects were transient and GJIC recovered after 4 h. VIN induced rapid hyperphosphorylation and internalization of gap junction protein connexin43, and both chemicals also activated MAPK ERK1/2 and p38. Effects on GJIC were not prevented by MEK1/2 inhibitor, but by an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), resveratrol, and in the case of VIN, also, by a p38 inhibitor. Estrogen (ER) and androgen receptor (AR) modulators (estradiol, ICI 182,780, HPTE, testosterone, flutamide, VIN M2) did not attenuate MXC or VIN effects on GJIC. Our data also indicate that the effects were elicited by the parental compounds of MXC and VIN. Our study provides new evidence that MXC and VIN dysregulate GJIC via mechanisms involving rapid activation of PC-PLC occurring independently of ER- or AR-dependent genomic signaling. Such alterations of rapid intercellular and intracellular signaling events involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Transgenerational effects and impact of compensatory responses to changes in breeding phenology on antipredator defenses.

Science.gov (United States)

Orizaola, Germán; Richter-Boix, Alex; Laurila, Anssi

2016-09-01

As organisms living in temperate environments often have only a short time window for growth and reproduction, their life-history strategies are expected to be influenced by these time constraints. Parents may alter the pace of offspring life-history as a response to changes in breeding phenology. However, the responses to changes in time constraints must be balanced with those against other stressors, such as predation, one of the strongest and more ubiquitous selective factors in nature. Here, after experimentally modifying the timing of breeding and hatching in the moor frog (Rana arvalis), we studied how compensatory responses to delayed breeding and hatching affect antipredator strategies in amphibian larvae. We examined the activity patterns, morphology and life-history responses in tadpoles exposed to different combinations of breeding and hatching delays in the presence and absence of predators. We found clear evidence of adaptive transgenerational effects since tadpoles from delayed breeding treatments increased growth and development independently of predation risk. The presence of predators reduced tadpole activity, tadpoles from delayed breeding treatments maintaining lower activity than non-delayed ones also in the absence of predators. Tadpoles reared with predators developed deeper tails and bodies, however, tadpoles from breeding delay treatments had reduced morphological defenses as compared to non-delayed individuals. No significant effects of hatching delay were detected in this study. Our study reveals that amphibian larvae exposed to breeding delay develop compensatory life-history responses even under predation risk, but these responses trade-off with the development of morphological antipredator defenses. These results suggest that under strong time constraints organisms are selected to develop fast growth and development responses, and rely on lower activity rates as their main antipredator defense. Examining how responses to changes in

Transgenerational developmental effects and genomic instability after X-irradiation of preimplantation embryos: Studies on two mouse strains

International Nuclear Information System (INIS)

Jacquet, P.; Buset, J.; Neefs, M.; Vankerkom, J.; Benotmane, M.A.; Derradji, H.; Hildebrandt, G.; Baatout, S.

2010-01-01

Recent results have shown that irradiation of a single cell, the zygote or 1-cell embryo of various mouse strains, could lead to congenital anomalies in the fetuses. In the Heiligenberger strain, a link between the radiation-induced congenital anomalies and the development of a genomic instability was also suggested. Moreover, further studies showed that in that strain, both congenital anomalies and genomic instability could be transmitted to the next generation. The aim of the experiments described in this paper was to investigate whether such non-targeted transgenerational effects could also be observed in two other radiosensitive mouse strains (CF1 and ICR), using lower radiation doses. Irradiation of the CF1 and ICR female zygotes with 0.2 or 0.4 Gy did not result in a decrease of their fertility after birth, when they had reached sexual maturity. Moreover, females of both strains that had been X-irradiated with 0.2 Gy exhibited higher rates of pregnancy, less resorptions and more living fetuses. Additionally, the mean weight of living fetuses in these groups had significantly increased. Exencephaly and dwarfism were observed in CF1 fetuses issued from control and X-irradiated females. In the control group of that strain, polydactyly and limb deformity were also found. The yields of abnormal fetuses did not differ significantly between the control and X-irradiated groups. Polydactyly, exencephaly and dwarfism were observed in fetuses issued from ICR control females. In addition to these anomalies, gastroschisis, curly tail and open eye were observed at low frequencies in ICR fetuses issued from X-irradiated females. Again, the frequencies of abnormal fetuses found in the different groups did not differ significantly. In both CF1 and ICR mouse strains, irradiation of female zygotes did not result in the development of a genomic instability in the next generation embryos. Overall, our results suggest that, at the moderate doses used, developmental defects

Transgenerational developmental effects and genomic instability after X-irradiation of preimplantation embryos: Studies on two mouse strains

Energy Technology Data Exchange (ETDEWEB)

Jacquet, P., E-mail: pjacquet@sckcen.be [Molecular and Cellular Biology, Institute for Environment, Health and Safety, SCK.CEN, Boeretang 200, B-2400 Mol (Belgium); Buset, J.; Neefs, M. [Molecular and Cellular Biology, Institute for Environment, Health and Safety, SCK.CEN, Boeretang 200, B-2400 Mol (Belgium); Vankerkom, J. [Division of Environmental Research, VITO, Boeretang 200, B-2400 Mol (Belgium); Benotmane, M.A.; Derradji, H. [Molecular and Cellular Biology, Institute for Environment, Health and Safety, SCK.CEN, Boeretang 200, B-2400 Mol (Belgium); Hildebrandt, G. [Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 9a, D-04103 Leipzig (Germany); Department of Radiotherapy, University of Rostock, Suedring 75, D-18059 Rostock (Germany); Baatout, S. [Molecular and Cellular Biology, Institute for Environment, Health and Safety, SCK.CEN, Boeretang 200, B-2400 Mol (Belgium)

2010-05-01

Recent results have shown that irradiation of a single cell, the zygote or 1-cell embryo of various mouse strains, could lead to congenital anomalies in the fetuses. In the Heiligenberger strain, a link between the radiation-induced congenital anomalies and the development of a genomic instability was also suggested. Moreover, further studies showed that in that strain, both congenital anomalies and genomic instability could be transmitted to the next generation. The aim of the experiments described in this paper was to investigate whether such non-targeted transgenerational effects could also be observed in two other radiosensitive mouse strains (CF1 and ICR), using lower radiation doses. Irradiation of the CF1 and ICR female zygotes with 0.2 or 0.4 Gy did not result in a decrease of their fertility after birth, when they had reached sexual maturity. Moreover, females of both strains that had been X-irradiated with 0.2 Gy exhibited higher rates of pregnancy, less resorptions and more living fetuses. Additionally, the mean weight of living fetuses in these groups had significantly increased. Exencephaly and dwarfism were observed in CF1 fetuses issued from control and X-irradiated females. In the control group of that strain, polydactyly and limb deformity were also found. The yields of abnormal fetuses did not differ significantly between the control and X-irradiated groups. Polydactyly, exencephaly and dwarfism were observed in fetuses issued from ICR control females. In addition to these anomalies, gastroschisis, curly tail and open eye were observed at low frequencies in ICR fetuses issued from X-irradiated females. Again, the frequencies of abnormal fetuses found in the different groups did not differ significantly. In both CF1 and ICR mouse strains, irradiation of female zygotes did not result in the development of a genomic instability in the next generation embryos. Overall, our results suggest that, at the moderate doses used, developmental defects

Transgenerational Effects of Trauma in Midlife: Evidence for Resilience and Vulnerability in Offspring of Holocaust Survivors

Science.gov (United States)

Shrira, Amit; Palgi, Yuval; Ben-Ezra, Menachem; Shmotkin, Dov

2010-01-01

Despite abundant research on offspring of Holocaust survivors (OHS), it is relatively unknown how they function in middle-age. Transgenerational effects of the Holocaust may be stronger among middle-aged OHS as they previously suffered from early inclement natal and postnatal environment and now face age-related decline. Yet, middle-aged OHS may successfully maintain the resilience they demonstrated at younger age. This study performed a wide-spectrum functional assessment of middle-aged OHS and comparisons (N = 364) drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe (SHARE-Israel). OHS, and especially those with two survivor parents, reported a higher sense of well-being, but more physical health problems than comparisons. The discussion provides possible explanations for this mixed functional profile. PMID:22267975

Alterations in the developing testis transcriptome following embryonic vinclozolin exposure.

Science.gov (United States)

Clement, Tracy M; Savenkova, Marina I; Settles, Matthew; Anway, Matthew D; Skinner, Michael K

2010-11-01

The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic days 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Categorization by major known functions of altered genes was performed. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin. Copyright © 2010 Elsevier Inc. All rights reserved.

Trans-generational parasite protection associated with paternal diet.

Science.gov (United States)

Sternberg, Eleanore D; de Roode, Jacobus C; Hunter, Mark D

2015-01-01

Multiple generations of hosts are often exposed to the same pathogens, favouring the evolution of trans-generational defences. Because females have more opportunities to transfer protective molecules to offspring, many studies have focused on maternally derived protection. However, males of many species can transfer compounds along with sperm, including chemicals that could provide protection. Here, we assess maternally and paternally derived protection in a monarch butterfly-protozoan parasite system where parasite resistance is heavily influenced by secondary plant chemicals, known as cardenolides, present in the larval diet of milkweed plants. We reared monarch butterflies on medicinal and non-medicinal milkweed species and then measured resistance of their offspring to infection. We also measured cardenolide content in adult monarchs reared on the two species, and in the eggs that they produced. We found that offspring were more resistant to infection when their fathers were reared on medicinal milkweed, while maternal diet had less of an effect. We also found that eggs contained the highest levels of cardenolides when both parents were reared on the medicinal species. Moreover, females reared on non-medicinal milkweed produced eggs with significantly higher levels of cardenolides if they mated with males reared on the medicinal milkweed species. However, we found an equivocal relationship between the cardenolides present in eggs and parasite resistance in the offspring. Our results demonstrate that males reared on medicinal plants can transfer protection to their offspring, but the exact mechanism remains unresolved. This suggests that paternal protection from parasitism might be important, particularly when there are environmental sources of parasite resistance and when males transfer spermatophores during mating. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

Transgenerational healing: Educating children in genesis of healthy children, with focus on nutrition, emotion, and epigenetic effects on brain development.

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House, Simon H

2013-01-01

Although our continuing evolution can never achieve our perfection, we long for our children's birth and health to be near-perfect. Many children are born healthy, though fewer than is possible. Birthing and health rapidly improved generally due to modern housing, sanitation and medicine, as well as birth interventions. Arguably interventions have exceeded the optimal level, without enough regard for natural physical and intuitive resources. Conception, often too easy, receives too little personal preparation unless a couple has problems. Nurturing the health of sperm and ovum seems hard to focus on, yet is needed by both parents - and even by the four grandparents. What are the key factors? Positive: The fields of hormones/emotions and of nutrition/metabolism. Negative: stress, poor nutrition, toxins, diseases; much being due to poverty. Positive and negative both have structural and also epigenetic effects. Interventions, essential or inessential, are seldom without negative side effects. Health can best, and most economically, be generated at the beginning of life, through healthy conception, gestation and birth. Understanding prime needs improves initial health. It also informs therapy of any early-life problems. Healing is therefore more efficient when transgenerational, and much more powerful than individual healing. My vision of healing is safeguarding our evolution in progress. Children's choices - eating, exercise, emotional attitudes and relationships - are already profoundly affecting any children they may have, their mental and physical health. The most practical starting point seems to be educating boys as well as girls. Childhood is therefore the time to educate them in choices. The correction of often unnoticed problems- nutrient deficits, toxins, uro-genital disease - has enabled nearly nine out of ten couples to bear fully healthy babies, even following severe problems - infertility, miscarriages, stillbirths and malformations. Correcting problems

Geographic structuring and transgenerational maternal effects shape germination in native, but not introduced, populations of a widespread plant invader.

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Alba, Christina; Moravcová, Lenka; Pyšek, Petr

2016-05-01

Germination is critical in determining species distributions and invasion dynamics. However, is it unclear how often invasive populations evolve germination characteristics different from native populations, because few studies have isolated genetic variation by using seed from garden-grown plants. Additionally, while herbivore-induced transgenerational effects are common, it is unknown whether maternal herbivory differentially shapes germination in native and introduced offspring. We explored germination in native and introduced populations of the North American invader Verbascum thapsus using seed from garden-grown maternal plants, half of which were protected from herbivores. To elucidate (1) germination niche breadth and (2) whether germination conditions affected expression of genetic structuring among populations, we germinated seed under four ecologically relevant temperature regimes. Native populations had a wide germination niche breadth, germinating as well as or better than introduced populations. At cooler temperatures, native populations exhibited a genetically based environmental cline indicative of local adaptation, with populations from warmer locales germinating better than populations from cooler locales. However, this cline was obscured when maternal plants were attacked by herbivores, revealing that local stressors can override the expression of geographic structuring. Introduced populations did not exhibit clinal variation, suggesting its disruption during the introduction process. Native and introduced populations have evolved genetic differences in germination. The result of this difference manifests in a wider germination niche breadth in natives, suggesting that the invasive behavior of V. thapsus in North America is attributable to other factors. © 2016 Botanical Society of America.

Environmentally toxicant exposures induced intragenerational transmission of liver abnormalities in mice

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Mohamed A. Al-Griw

2017-08-01

Full Text Available Environmental toxicants such as chemicals, heavy metals, and pesticides have been shown to promote transgenerational inheritance of abnormal phenotypes and/or diseases to multiple subsequent generations following parental and/ or ancestral exposures. This study was designed to examine the potential transgenerational action of the environmental toxicant trichloroethane (TCE on transmission of liver abnormality, and to elucidate the molecular etiology of hepatocyte cell damage. A total of thirty two healthy immature female albino mice were randomly divided into three equal groups as follows: a sham group, which did not receive any treatment; a vehicle group, which received corn oil alone, and TCE treated group (3 weeks, 100 μg/kg i.p., every 4th day. The F0 and F1 generation control and TCE populations were sacrificed at the age of four months, and various abnormalities histpathologically investigated. Cell death and oxidative stress indices were also measured. The present study provides experimental evidence for the inheritance of environmentally induced liver abnormalities in mice. The results of this study show that exposure to the TCE promoted adult onset liver abnormalities in F0 female mice as well as unexposed F1 generation offspring. It is the first study to report a transgenerational liver abnormalities in the F1 generation mice through maternal line prior to gestation. This finding was based on careful evaluation of liver histopathological abnormalities, apoptosis of hepatocytes, and measurements of oxidative stress biomarkers (lipid peroxidation, protein carbonylation, and nitric oxide in control and TCE populations. There was an increase in liver histopathological abnormalities, cell death, and oxidative lipid damage in F0 and F1 hepatic tissues of TCE treated group. In conclusion, this study showed that the biological and health impacts of environmental toxicant TCE do not end in maternal adults, but are passed on to offspring

Maternal antecedents of adiposity and studying the transgenerational role of hyperglycemia and insulin (MAASTHI): a prospective cohort study : Protocol of birth cohort at Bangalore, India.

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Babu, Giridhara R; Murthy, Gvs; Deepa, R; Yamuna; Prafulla; Kumar, H Kiran; Karthik, Maithili; Deshpande, Keerti; Benjamin Neelon, Sara E; Prabhakaran, D; Kurpad, Anura; Kinra, Sanjay

2016-10-14

India is experiencing an epidemic of obesity-hyperglycaemia, which coincides with child bearing age for women. The epidemic can be sustained and augmented through transgenerational transmission of adiposity and glucose intolerance in women. This presents an opportunity for exploring a clear strategy for the control of this epidemic in India. We conducted a study between November 2013 and May 2015 to inform the design of a large pregnancy cohort study. Based on the findings of this pilot, we developed the protocol for the proposed birth cohort of 5000 women, the recruitment for which will start in April 2016. The protocol of the study documents the processes which aim at advancing the available knowledge, linking several steps in the evolution of obesity led hyperglycemia. Maternal Antecedents of Adiposity and Studying the Transgenerational role of Hyperglycemia and Insulin (MAASTHI) is a cohort study in the public health facilities in Bangalore, India. The objective of MAASTHI is to prospectively assess the effects of glucose levels in pregnancy on the risk of adverse infant outcomes, especially in predicting the possible risk markers of later chronic diseases. The primary objective of the proposed study is to investigate the effect of glucose levels in pregnancy on skinfold thickness (adiposity) in infancy as a marker of future obesity and diabetes in offspring. The secondary objective is to assess the association between psychosocial environment of mothers and adverse neonatal outcomes including adiposity. The study aims to recruit 5000 pregnant women and follow them and their offspring for a period of 4 years. The institutional review board at The Indian Institute of Public Health (IIPH)-H, Bangalore, Public Health Foundation of India has approved the protocol. All participants are required to provide written informed consent. The findings from this study may help to address important questions on screening and management of high blood sugar in pregnancy. It

The role of adaptive trans-generational plasticity in biological invasions of plants.

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Dyer, Andrew R; Brown, Cynthia S; Espeland, Erin K; McKay, John K; Meimberg, Harald; Rice, Kevin J

2010-03-01

High-impact biological invasions often involve establishment and spread in disturbed, high-resource patches followed by establishment and spread in biotically or abiotically stressful areas. Evolutionary change may be required for the second phase of invasion (establishment and spread in stressful areas) to occur. When species have low genetic diversity and short selection history, within-generation phenotypic plasticity is often cited as the mechanism through which spread across multiple habitat types can occur. We show that trans-generational plasticity (TGP) can result in pre-adapted progeny that exhibit traits associated with increased fitness both in high-resource patches and in stressful conditions. In the invasive sedge, Cyperus esculentus, maternal plants growing in nutrient-poor patches can place disproportional number of propagules into nutrient-rich patches. Using the invasive annual grass, Aegilops triuncialis, we show that maternal response to soil conditions can confer greater stress tolerance in seedlings in the form of greater photosynthetic efficiency. We also show TGP for a phenological shift in a low resource environment that results in greater stress tolerance in progeny. These lines of evidence suggest that the maternal environment can have profound effects on offspring success and that TGP may play a significant role in some plant invasions.

Transgenerational plasticity and climate change experiments: Where do we go from here?

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Donelson, Jennifer M; Salinas, Santiago; Munday, Philip L; Shama, Lisa N S

2018-01-01

Phenotypic plasticity, both within and across generations, is an important mechanism that organisms use to cope with rapid climate change. While an increasing number of studies show that plasticity across generations (transgenerational plasticity or TGP) may occur, we have limited understanding of key aspects of TGP, such as the environmental conditions that may promote it, its relationship to within-generation plasticity (WGP) and its role in evolutionary potential. In this review, we consider how the detection of TGP in climate change experiments is affected by the predictability of environmental variation, as well as the timing and magnitude of environmental change cues applied. We also discuss the need to design experiments that are able to distinguish TGP from selection and TGP from WGP in multigenerational experiments. We conclude by suggesting future research directions that build on the knowledge to date and admit the limitations that exist, which will depend on the way environmental change is simulated and the type of experimental design used. Such an approach will open up this burgeoning area of research to a wider variety of organisms and allow better predictive capacity of the role of TGP in the response of organisms to future climate change. © 2017 John Wiley & Sons Ltd.

Chronic transgenerational vitamin B12 deficiency of severe and moderate magnitudes modulates adiposity-probable underlying mechanisms.

Science.gov (United States)

Ghosh, Shampa; Sinha, Jitendra Kumar; Muralikrishna, Bojanapalli; Putcha, Uday Kumar; Raghunath, Manchala

2017-05-06

We have demonstrated previously that severe but not moderate vitamin B12 deficiency altered body composition and induced adiposity in female C57BL/6 mice. This study aims to elucidate the effects of chronic transgenerational dietary vitamin B12 restriction on body composition and various biochemical parameters in the F1 generation offspring of our mouse models of severe and moderate vitamin B12 deficiency established earlier. Female weanling C57BL/6 mice received, ad libitum, for 4 weeks a (i) control diet, (ii) vitamin B12-restricted diet with pectin as dietary fiber (severely deficient diet), or (iii) vitamin B12-restricted diet with cellulose as dietary fiber (moderately deficient diet) and then mated with control males. The offspring of control and severely deficient dams continued on the respective diets of their mothers. Few moderately deficient dams were rehabilitated to control diet from parturition and their pups were weaned to control diet. Also, some offspring born to moderately B12 deficient dams were weaned to control diet, while others continued on the same diet as their mothers. Various parameters were determined in the F1 offspring after 12 and 36 weeks of feeding. The results indicate that both severe and moderate maternal vitamin B12 restrictions were associated with accelerated catch-up growth, increased body fat percentage, visceral adiposity, dyslipidemia, fasting hyperglycemia and insulin resistance in the F1 offspring. Inflammation, increased glucocorticoid and oxidative stress and poor antioxidant defence probably underlie these adverse effects. Rehabilitation from parturition but not weaning was beneficial in delaying the onset of the adverse outcomes in the offspring. © 2016 BioFactors, 43(3):400-414, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

The C. elegans CSR-1 argonaute pathway counteracts epigenetic silencing to promote germline gene expression.

Science.gov (United States)

Seth, Meetu; Shirayama, Masaki; Gu, Weifeng; Ishidate, Takao; Conte, Darryl; Mello, Craig C

2013-12-23

Organisms can develop adaptive sequence-specific immunity by reexpressing pathogen-specific small RNAs that guide gene silencing. For example, the C. elegans PIWI-Argonaute/piwi-interacting RNA (piRNA) pathway recruits RNA-dependent RNA polymerase (RdRP) to foreign sequences to amplify a transgenerational small-RNA-induced epigenetic silencing signal (termed RNAe). Here, we provide evidence that, in addition to an adaptive memory of silenced sequences, C. elegans can also develop an opposing adaptive memory of expressed/self-mRNAs. We refer to this mechanism, which can prevent or reverse RNAe, as RNA-induced epigenetic gene activation (RNAa). We show that CSR-1, which engages RdRP-amplified small RNAs complementary to germline-expressed mRNAs, is required for RNAa. We show that a transgene with RNAa activity also exhibits accumulation of cognate CSR-1 small RNAs. Our findings suggest that C. elegans adaptively acquires and maintains a transgenerational CSR-1 memory that recognizes and protects self-mRNAs, allowing piRNAs to recognize foreign sequences innately, without the need for prior exposure

Grandparental effects in marine sticklebacks: transgenerational plasticity across multiple generations.

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Shama, L N S; Wegner, K M

2014-11-01

Nongenetic inheritance mechanisms such as transgenerational plasticity (TGP) can buffer populations against rapid environmental change such as ocean warming. Yet, little is known about how long these effects persist and whether they are cumulative over generations. Here, we tested for adaptive TGP in response to simulated ocean warming across parental and grandparental generations of marine sticklebacks. Grandparents were acclimated for two months during reproductive conditioning, whereas parents experienced developmental acclimation, allowing us to compare the fitness consequences of short-term vs. prolonged exposure to elevated temperature across multiple generations. We found that reproductive output of F1 adults was primarily determined by maternal developmental temperature, but carry-over effects from grandparental acclimation environments resulted in cumulative negative effects of elevated temperature on hatching success. In very early stages of growth, F2 offspring reached larger sizes in their respective paternal and grandparental environment down the paternal line, suggesting that other factors than just the paternal genome may be transferred between generations. In later growth stages, maternal and maternal granddam environments strongly influenced offspring body size, but in opposing directions, indicating that the mechanism(s) underlying the transfer of environmental information may have differed between acute and developmental acclimation experienced by the two generations. Taken together, our results suggest that the fitness consequences of parental and grandparental TGP are highly context dependent, but will play an important role in mediating some of the impacts of rapid climate change in this system. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Effect of the transgenerational exposure to elevated CO2 on the drought response of winter wheat

DEFF Research Database (Denmark)

Li, Yafei; Li, Xiangnan; Yu, Jingjie

2017-01-01

Abstract Climate change predicts more frequent drought spells along with an elevation in atmospheric CO2 concentration (e[CO2]). Although the responses of winter wheat (Triticum aestivum L.) plants to drought or a single generation exposure to e[CO2] have been well documented, the transgenerational...... effect of e[CO2] in combination of drought on stomatal behavior, plant water consumption and water use efficiency (WUE) have not been investigated. Seeds harvested from plants after two generations (2014–2015) continuously grown in ambient CO2 (a[CO2], 400 μmol L−1) and e[CO2] (800 μmol L−1) were sown...... in 4 L pots, and the plants were grown separately in greenhouse cells with either a[CO2] or e[CO2]. At stem elongation stage, in each of the cells half of the plants were subjected to progressive drought stress until all the plant available soil water was depleted, and the other half were well-watered...

Chromatin resetting mechanisms preventing trangenerational inheritance of epigenetic states

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Mayumi eIwasaki

2015-05-01

Full Text Available Epigenetic regulation can be altered by environmental cues including abiotic and biotic stresses. In most cases, environmentally-induced epigenetic changes are transient, but in some cases they are maintained for extensive periods of time and may even be transmitted to the next generation. However, the underlying mechanisms of transgenerational transmission of environmentally-induced epigenetic states remain largely unknown. Such traits can be adaptive, but also can have negative consequences if the parentally inherited epigenetic memory interferes with canonical environmental responses of the progeny. This review highlights recent insights into the mechanisms preventing transgenerational transmission of environmentally-induced epigenetic states in plants, which resemble those of germline reprogramming in mammals.

Preconception paternal bisphenol A exposure induces sex-specific anxiety and depression behaviors in adult rats.

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Ying Fan

Full Text Available Bisphenol A (BPA, an environmental endocrine-disrupting compound, has drawn a great attention for its adverse effect on behavioral development. Maternal exposure to this compound has been reported to induce anxiety and depression in offspring, but the effect of its paternal exposure is rarely discussed. This study investigated whether preconception paternal BPA exposure can affect the emotions of male rats and their offspring. Eighteen adult male rats (F0 received either a vehicle or 50 μg/kg/day BPA diet for 21 weeks and were then mated with non-exposed females to produce offspring (F1. The affective behaviors of F0 and F1 rats were evaluated in the open-field test, the elevated-plus maze and the forced swimming test, and their serum corticosterone were then examined. BPA exposure induced increased anxiety behaviors along with increased serum corticosterone in F0 rats. This paternal exposure also led to increased anxiety behaviors in F1 females and aggravated depression behaviors in both sexes of F1 rats. Furthermore, only F1 females exhibited increased serum corticosterone. Overall, these data indicate that preconception paternal exposure to a low dose of BPA may induce transgenerational sex-specific impairments in the affection of adult rats.

Transgenerational shifts in reproduction hormesis in green peach aphid exposed to low concentrations of imidacloprid.

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Murali-Mohan Ayyanath

Full Text Available Hormesis is a biphasic phenomenon that in toxicology is characterized by low-dose stimulation and high-dose inhibition. It has been observed in a wide range of organisms in response to many chemical stressors, including insects exposed to pesticides, with potential repercussions for agriculture and pest management. To address questions related to the nature of the dose-response and potential consequences on biological fitness, we examined transgenerational hormesis in the green peach aphid, Myzus persicae, when exposed to sublethal concentrations of the insecticide imidacloprid. A hormetic response in the form of increased reproduction was consistently observed and a model previously developed to test for hormesis adequately fit some of our data. However, the nature of the dose-response differed within and across generations depending upon the duration and mode of exposure. Decreased reproduction in intermediate generations confirmed that fitness tradeoffs were a consequence of the hormetic response. However, recovery to levels of reproduction equal to that of controls in subsequent generations and significantly greater total reproduction after four generations suggested that biological fitness was increased by exposure to low concentrations of the insecticide, even when insects were continuously exposed to the stressor. This was especially evident in a greenhouse experiment where the instantaneous rate of population increase almost doubled and total aphid production more than quadrupled when aphids were exposed to potato plants systemically treated with low amounts of imidacloprid. Our results show that although fitness tradeoffs do occur with hormetic responses, this does not necessarily compromise overall biological fitness.

Individual-specific transgenerational marking of fish populations based on a barium dual-isotope procedure.

Science.gov (United States)

Huelga-Suarez, Gonzalo; Moldovan, Mariella; Garcia-Valiente, America; Garcia-Vazquez, Eva; Alonso, J Ignacio Garcia

2012-01-03

The present study focuses on the development and evaluation of an individual-specific transgenerational marking procedure using two enriched barium isotopes, (135)Ba and (137)Ba, mixed at a given and selectable molar ratio. The method is based on the deconvolution of the isotope patterns found in the sample into four molar contribution factors: natural xenon (Xe nat), natural barium (Ba nat), Ba135, and Ba137. The ratio of molar contributions between Ba137 and Ba135 is constant and independent of the contribution of natural barium in the sample. This procedure was tested in brown trout ( Salmo trutta ) kept in captivity. Trout were injected with three different Ba137/Ba135 isotopic signatures ca. 7 months and 7 days before spawning to compare the efficiency of the marking procedure at long and short term, respectively. The barium isotopic profiles were measured in the offspring by means of inductively coupled plasma mass spectrometry. Each of the three different isotopic signatures was unequivocally identified in the offspring in both whole eggs and larvae. For 9 month old offspring, the characteristic barium isotope signatures could also be detected in the otoliths even in the presence of a high and variable amount of barium of natural isotope abundance. In conclusion, it can be stated that the proposed dual-isotope marking is inheritable and can be detected after both long-term and short-term marking. Furthermore, the dual-isotope marking can be made individual-specific, so that it allows identification of offspring from a single individual or a group of individuals within a given fish group. © 2011 American Chemical Society

Transgenerational programming of longevity and reproduction by post-eclosion dietary manipulation in Drosophila

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Xia, Brian; de Belle, Steven

2016-01-01

Accumulating evidence suggests that early-life diet may program one's health status by causing permanent alternations in specific organs, tissues, or metabolic or homeostatic pathways, and such programming effects may propagate across generations through heritable epigenetic modifications. However, it remains uninvestigated whether postnatal dietary changes may program longevity across generations. To address this question of important biological and public health implications, newly-born flies (F0) were collected and subjected to various post-eclosion dietary manipulations (PDMs) with different protein-carbohydrate (i.e., LP, IP or HP for low-, intermediate- or high-protein) contents or a control diet (CD). Longevity and fecundity analyses were performed with these treated F0 flies and their F1, F2 and F3 offspring, while maintained on CD at all times. The LP and HP PDMs shortened longevity, while the IP PDM extended longevity significantly up to the F3 generation. Furthermore, the LP reduced while the IP PDM increased lifetime fecundity across the F0-F2 generations. Our observations establish the first animal model for studying transgenerational inheritance of nutritional programming of longevity, making it possible to investigate the underlying epigenetic mechanisms and identify gene targets for drug discovery in future studies. PMID:27025190

Preconditioning in the reef-building coral Pocillopora damicornis and the potential for trans-generational acclimatization in coral larvae under future climate change conditions.

Science.gov (United States)

Putnam, Hollie M; Gates, Ruth D

2015-08-01

Coral reefs are globally threatened by climate change-related ocean warming and ocean acidification (OA). To date, slow-response mechanisms such as genetic adaptation have been considered the major determinant of coral reef persistence, with little consideration of rapid-response acclimatization mechanisms. These rapid mechanisms such as parental effects that can contribute to trans-generational acclimatization (e.g. epigenetics) have, however, been identified as important contributors to offspring response in other systems. We present the first evidence of parental effects in a cross-generational exposure to temperature and OA in reef-building corals. Here, we exposed adults to high (28.9°C, 805 µatm P(CO2)) or ambient (26.5°C, 417 µatm P(CO2)) temperature and OA treatments during the larval brooding period. Exposure to high treatment negatively affected adult performance, but their larvae exhibited size differences and metabolic acclimation when subsequently re-exposed, unlike larvae from parents exposed to ambient conditions. Understanding the innate capacity corals possess to respond to current and future climatic conditions is essential to reef protection and maintenance. Our results identify that parental effects may have an important role through (1) ameliorating the effects of stress through preconditioning and adaptive plasticity, and/or (2) amplifying the negative parental response through latent effects on future life stages. Whether the consequences of parental effects and the potential for trans-generational acclimatization are beneficial or maladaptive, our work identifies a critical need to expand currently proposed climate change outcomes for corals to further assess rapid response mechanisms that include non-genetic inheritance through parental contributions and classical epigenetic mechanisms. © 2015. Published by The Company of Biologists Ltd.

Transgenerational effects of nutrition are different for sons and daughters.

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Zizzari, Z V; van Straalen, N M; Ellers, J

2016-07-01

Food shortage is an important selective factor shaping animal life-history trajectories. Yet, despite its role, many aspects of the interaction between parental and offspring food environments remain unclear. In this study, we measured developmental plasticity in response to food availability over two generations and tested the relative contribution of paternal and maternal food availability to the performance of offspring reared under matched and mismatched food environments. We applied a cross-generational split-brood design using the springtail Orchesella cincta, which is found in the litter layer of temperate forests. The results show adverse effects of food limitation on several life-history traits and reproductive performance of both parental sexes. Food conditions of both parents contributed to the offspring phenotypic variation, providing evidence for transgenerational effects of diet. Parental diet influenced sons' age at maturity and daughters' weight at maturity. Specifically, being born to food-restricted parents allowed offspring to alleviate the adverse effects of food limitation, without reducing their performance under well-fed conditions. Thus, parents raised on a poor diet primed their offspring for a more efficient resource use. However, a mismatch between maternal and offspring food environments generated sex-specific adverse effects: female offspring born to well-fed mothers showed a decreased flexibility to deal with low-food conditions. Notably, these maternal effects of food availability were not observed in the sons. Finally, we found that the relationship between age and size at maturity differed between males and females and showed that offspring life-history strategies in O. cincta are primed differently by the parents. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Molecular signatures of transgenerational response to ocean acidification in a species of reef fish

KAUST Repository

Schunter, Celia Marei; Welch, Megan J.; Ryu, Tae Woo; Zhang, Huoming; Berumen, Michael L.; Nilsson, Gö ran E.; Munday, Philip L.; Ravasi, Timothy

2016-01-01

The impact of ocean acidification on marine ecosystems will depend on species capacity to adapt. Recent studies show that the behaviour of reef fishes is impaired at projected CO levels; however, individual variation exists that might promote adaptation. Here, we show a clear signature of parental sensitivity to high CO in the brain molecular phenotype of juvenile spiny damselfish, Acanthochromis polyacanthus, primarily driven by circadian rhythm genes. Offspring of CO -tolerant and CO -sensitive parents were reared at near-future CO (754 μatm) or present-day control levels (414 μatm). By integrating 33 brain transcriptomes and proteomes with a de novo assembled genome we investigate the molecular responses of the fish brain to increased CO and the expression of parental tolerance to high CO in the offspring molecular phenotype. Exposure to high CO resulted in differential regulation of 173 and 62 genes and 109 and 68 proteins in the tolerant and sensitive groups, respectively. Importantly, the majority of differences between offspring of tolerant and sensitive parents occurred in high CO conditions. This transgenerational molecular signature suggests that individual variation in CO sensitivity could facilitate adaptation of fish populations to ocean acidification.

Molecular signatures of transgenerational response to ocean acidification in a species of reef fish

KAUST Repository

Schunter, Celia Marei

2016-07-29

The impact of ocean acidification on marine ecosystems will depend on species capacity to adapt. Recent studies show that the behaviour of reef fishes is impaired at projected CO levels; however, individual variation exists that might promote adaptation. Here, we show a clear signature of parental sensitivity to high CO in the brain molecular phenotype of juvenile spiny damselfish, Acanthochromis polyacanthus, primarily driven by circadian rhythm genes. Offspring of CO -tolerant and CO -sensitive parents were reared at near-future CO (754 μatm) or present-day control levels (414 μatm). By integrating 33 brain transcriptomes and proteomes with a de novo assembled genome we investigate the molecular responses of the fish brain to increased CO and the expression of parental tolerance to high CO in the offspring molecular phenotype. Exposure to high CO resulted in differential regulation of 173 and 62 genes and 109 and 68 proteins in the tolerant and sensitive groups, respectively. Importantly, the majority of differences between offspring of tolerant and sensitive parents occurred in high CO conditions. This transgenerational molecular signature suggests that individual variation in CO sensitivity could facilitate adaptation of fish populations to ocean acidification.

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

Keywords. cytosine methylation; DNA methylation mechanisms; DNA demethylation mechanisms; Darwinian-cum-Lamarckian evolution; epialleles; epigenetic modifications; genetic recombination; heritable induced defence; mutational hotspots; transgenerational inheritance.

Influence the technogenic disaster at radionuclide contaminated Chernobyl zone on transgeneration changes of plants

International Nuclear Information System (INIS)

Rashydov, N.

2017-01-01

Some of the territories have naturally increased level of radiation as areas of native radioecological anomalies, but others were polluted as a result of nuclear weapon testing, nuclear waste leakage, and nuclear power plants disasters, such as Chernobyl nuclear power plant (CNPP) and Fukushima. Eventually, the large areas have been strong contaminated with radioactivity isotopes for long term. Despite more than thirty years aftermath the explosion of the CNPP accident, the problems coming from the high radionuclide contamination of the environment and the effects of chronic radiation on living organisms still remain relevant. Because the recent tragedy at the Fukushima Nuclear Power Plant in Japan is chillingly reminiscent of the world's worst nuclear disaster at Chernobyl, Ukraine in 1986. Our research addressing the effects of chronic ionizing radiation on plants, the ongoing success of plants adaptation and transgeneration changes in radio-contaminated Chernobyl area was revealed. The focus our investigation is on a role of the small dose chronic radiation due to plant biodiversity processes because it is a common adverse environmental toxicology factor. In order to characterize proteomes of plants adapting to biodiversity at radio-contaminated Chernobyl area we established non-radioactive and radio-contaminated experimental fields.

Stress-induced variation in evolution: from behavioural plasticity to genetic assimilation.

Science.gov (United States)

Badyaev, Alexander V

2005-05-07

Extreme environments are closely associated with phenotypic evolution, yet the mechanisms behind this relationship are poorly understood. Several themes and approaches in recent studies significantly further our understanding of the importance that stress-induced variation plays in evolution. First, stressful environments modify (and often reduce) the integration of neuroendocrinological, morphological and behavioural regulatory systems. Second, such reduced integration and subsequent accommodation of stress-induced variation by developmental systems enables organismal 'memory' of a stressful event as well as phenotypic and genetic assimilation of the response to a stressor. Third, in complex functional systems, a stress-induced increase in phenotypic and genetic variance is often directional, channelled by existing ontogenetic pathways. This accounts for similarity among individuals in stress-induced changes and thus significantly facilitates the rate of adaptive evolution. Fourth, accumulation of phenotypically neutral genetic variation might be a common property of locally adapted and complex organismal systems, and extreme environments facilitate the phenotypic expression of this variance. Finally, stress-induced effects and stress-resistance strategies often persist for several generations through maternal, ecological and cultural inheritance. These transgenerational effects, along with both the complexity of developmental systems and stressor recurrence, might facilitate genetic assimilation of stress-induced effects. Accumulation of phenotypically neutral genetic variance by developmental systems and phenotypic accommodation of stress-induced effects, together with the inheritance of stress-induced modifications, ensure the evolutionary persistence of stress-response strategies and provide a link between individual adaptability and evolutionary adaptation.

Detection of transgenerational barium dual-isotope marks in salmon otoliths by means of LA-ICP-MS.

Science.gov (United States)

Huelga-Suarez, Gonzalo; Fernández, Beatriz; Moldovan, Mariella; García Alonso, J Ignacio

2013-03-01

The present study evaluates the use of an individual-specific transgenerational barium dual-isotope procedure and its application to salmon specimens from the Sella River (Asturias, Spain). For such a purpose, the use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) in combination with multiple linear regression for the determination of the isotopic mark in the otoliths of the specimens is presented. In this sense, a solution in which two barium-enriched isotopes ((137)Ba and (135)Ba) were mixed at a molar ratio of ca. 1:3 (N Ba137/N Ba135) was administered to eight returning females caught during the spawning period. After injection, these females, as well as their offspring, were reared in a governmental hatchery located in the council of Cangas de Onís (Asturias, Spain). For comparison purposes, as well as for a time-monitoring control, egg and larva data obtained by solution analysis ICP-MS are also given. Otoliths (9-month-old juveniles) of marked offspring were analysed by LA-ICP-MS demonstrating a 100 % marking efficacy of this methodology. The capabilities of the molar fraction approach for 2D imaging of fish otoliths are also addressed.

Transgenerational soil-mediated differences between plants experienced or naïve to a grass invasion.

Science.gov (United States)

Deck, Anna; Muir, Adrianna; Strauss, Sharon

2013-10-01

Invasive species may undergo rapid change as they invade. Native species persisting in invaded areas may also experience rapid change over this short timescale relative to native populations in uninvaded areas. We investigated the response of the native Achillea millefolium to soil from Holcus lanatus-invaded and uninvaded areas, and we sought to determine whether differential responses between A. millefolium from invaded (invader experienced) and uninvaded (invader naïve) areas were mediated by soil community changes. Plants grown from seed from experienced and naïve areas responded differently to invaded and uninvaded soil with respect to germination time, biomass, and height. Overall, experienced plants grew faster and taller than their naïve counterparts. Naïve native plants showed negative feedbacks with their home soil and positive feedbacks with invaded soil; experienced plants were less responsive to soil differences. Our results suggest that native plants naïve to invasion may be more sensitive to soil communities than experienced plants, consistent with recent studies. While differences between naïve and experienced plants are transgenerational, our design cannot differentiate between differences that are genetically based, plastic, or both. Regardless, our results highlight the importance of seed source and population history in restoration, emphasizing the restoration potential of experienced seed sources.

Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation?

Science.gov (United States)

Morgan, William F.

2003-01-01

A number of nontargeted and delayed effects associated with radiation exposure have now been described. These include radiation-induced genomic instability, death-inducing and bystander effects, clastogenic factors and transgenerational effects. It is unlikely that these nontargeted effects are directly induced by cellular irradiation. Instead, it is proposed that some as yet to be identified secreted factor can be produced by irradiated cells that can stimulate effects in nonirradiated cells (death-inducing and bystander effects, clastogenic factors) and perpetuate genomic instability in the clonally expanded progeny of an irradiated cell. The proposed factor must be soluble and capable of being transported between cells by cell-to-cell gap junction communication channels. Furthermore, it must have the potential to stimulate cellular cytokines and/or reactive oxygen species. While it is difficult to imagine a role for such a secreted factor in contributing to transgenerational effects, the other nontargeted effects of radiation may all share a common mechanism.

Mechanisms of transgenerational inheritance of addictive-like behaviors.

Science.gov (United States)

Vassoler, F M; Sadri-Vakili, G

2014-04-04

Genetic factors are implicated in the heritability of drug abuse. However, even with advances in current technology no specific genes have been identified that are critical for the transmission of drug-induced phenotypes to subsequent generations. It is now evident that epigenetic factors contribute to disease heritability and represent a link between genes and the environment. Recently, epigenetic mechanisms have been shown to underlie drug-induced structural, synaptic, and behavioral plasticity by coordinating the expression of gene networks within the brain. Therefore, the epigenome provides a direct mechanism for drugs of abuse to influence the genetic events involved in the development of addiction as well as its heritability to subsequent generations. In this review we discuss the mechanisms underlying intergenerational epigenetic transmission, highlight studies that demonstrate this phenomenon with particular attention to the field of addiction, and identify gaps for future studies. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

THE ELUCIDATION OF STRESS MEMORY INHERITANCE IN BRASSICA RAPA PLANTS

Directory of Open Access Journals (Sweden)

Andriy eBilichak

2015-01-01

Full Text Available Plants are able to maintain the memory of stress exposure throughout their ontogenesis and faithfully propagate it into the next generation. Recent evidence argues for the epigenetic nature of this phenomenon. Small RNAs (smRNAs are one of the vital epigenetic factors because they can both affect gene expression at the place of their generation and maintain non-cell-autonomous gene regulation. Here, we have made an attempt to decipher the contribution of smRNAs to the heat-shock-induced transgenerational inheritance in Brassica rapa plants using sequencing technology. To do this, we have generated comprehensive profiles of a transcriptome and a small RNAome (smRNAome from somatic and reproductive tissues of stressed plants and their untreated progeny. We have demonstrated that the highest tissue-specific alterations in the transcriptome and smRNAome profile are detected in tissues that were not directly exposed to stress, namely, in the endosperm and pollen. Importantly, we have revealed that the progeny of stressed plants exhibit the highest fluctuations at the smRNAome level but not at the transcriptome level. Additionally, we have uncovered the existence of heat-inducible and transgenerationally transmitted tRNA-derived small RNA fragments in plants. Finally, we suggest that miR168 and braAGO1 are involved in the stress-induced transgenerational inheritance in plants.

Epigenetics in radiation biology: a new research frontier

International Nuclear Information System (INIS)

Agarwal, Sural

2014-01-01

The number of people that receive exposure to ionizing radiation (IR) via occupational, diagnostic, or treatment-related modalities is progressively rising. It is now accepted that the negative consequences of radiation exposure are not isolated to exposed cells or individuals. Exposure to IR can induce genome instability in the germ line, and is further associated with transgenerational genomic instability in the off spring of exposed males. The exact molecular mechanisms for transgenerational genome instability have yet to be elucidated, although there is support for it being an epigenetically induced phenomenon. This review is centered on the long-term biological effects associated with IR exposure, mainly focusing on the epigentic mechanisms and also some facts about whether dental radiology (IOPA, OPG, CT, MRI, CBCT) can lead to carcinogenesis. (author)

Transgenerational Inheritance of Increased Fat Depot Size, Stem Cell Reprogramming, and Hepatic Steatosis Elicited by Prenatal Exposure to the Obesogen Tributyltin in Mice

Science.gov (United States)

Chamorro-García, Raquel; Sahu, Margaret; Abbey, Rachelle J.; Laude, Jhyme; Pham, Nhieu

2013-01-01

Background: We have previously shown that exposure to tributyltin (TBT) modulates critical steps of adipogenesis through RXR/PPARγ and that prenatal TBT exposure predisposes multipotent mesenchymal stem cells (MSCs) to become adipocytes by epigenetic imprinting into the memory of the MSC compartment. Objective: We tested whether the effects of prenatal TBT exposure were heritable in F2 and F3 generations. Methods: We exposed C57BL/6J female mice (F0) to DMSO vehicle, the pharmaceutical obesogen rosiglitazone (ROSI), or TBT (5.42, 54.2, or 542 nM) throughout pregnancy via the drinking water. F1 offspring were bred to yield F2, and F2 mice were bred to produce F3. F1 animals were exposed in utero and F2 mice were potentially exposed as germ cells in the F1, but F3 animals were never exposed to the chemicals. We analyzed the effects of these exposures on fat depot weights, adipocyte number, adipocyte size, MSC programming, hepatic lipid accumulation, and hepatic gene expression in all three generations. Discussion: Prenatal TBT exposure increased most white adipose tissue (WAT) depot weights, adipocyte size, and adipocyte number, and reprogrammed MSCs toward the adipocyte lineage at the expense of bone in all three generations. Prenatal TBT exposure led to hepatic lipid accumulation and up-regulated hepatic expression of genes involved in lipid storage/transport, lipogenesis, and lipolysis in all three subsequent generations. Conclusions: Prenatal TBT exposure produced transgenerational effects on fat depots and induced a phenotype resembling nonalcoholic fatty liver disease through at least the F3 generation. These results show that early-life obesogen exposure can have lasting effects. PMID:23322813

Fetal growth and developmental programming.

Science.gov (United States)

Galjaard, Sander; Devlieger, Roland; Van Assche, Frans A

2013-01-01

The environment in utero and in early neonatal life may induce a permanent response in the fetus and the newborn, leading to enhanced susceptibility to later diseases. This review concentrates on the role and mechanisms of events during the antenatal and immediate postnatal period resulting in later life diseases, concentrating on abnormal growth patterns of the fetus. Fetal overgrowth is related to exposure to a diabetic intra uterine environment, increasing the vulnerability to transgenerational obesity and hence an increased sensitivity to more diabetic mothers. This effect has been supported by animal data. Fetal growth restriction is complex due to malnutrition in utero, catch up growth due to a high caloric intake and low physical activity in later life. Metabolic changes and a transgenerational effect of intra uterine malnutrition has been supported by animal data. In recent years the discovery of alterations of the genome due to different influences during embryonic life, called epigenetics, has led to the phenomenon of fetal programming resulting in changing transgenerational metabolic effects.

Irradiation of rainbow trout at early life stages results in trans-generational effects including the induction of a bystander effect in non-irradiated fish.

Science.gov (United States)

Smith, Richard W; Seymour, Colin B; Moccia, Richard D; Mothersill, Carmel E

2016-02-01

The bystander effect, a non-targeted effect (NTE) of radiation, which describes the response by non-irradiated organisms to signals emitted by irradiated organisms, has been documented in a number of fish species. However transgenerational effects of radiation (including NTE) have yet to be studied in fish. Therefore rainbow trout, which were irradiated as eggs at 48h after fertilisation, eyed eggs, yolk sac larvae or first feeders, were bred to generate a F1 generation and these F1 fish were bred to generate a F2 generation. F1 and F2 fish were swam with non-irradiated bystander fish. Media from explants of F1 eyed eggs, F1 one year old fish gill and F1 two year old fish gill and spleen samples, and F2 two year old gill and spleen samples, as well as from bystander eggs/fish, was used to treat a reporter cell line, which was then assayed for changes in cellular survival/growth. The results were complex and dependent on irradiation history, age (in the case of the F1 generation), and were tissue specific. For example, irradiation of one parent often resulted in effects not seen with irradiation of both parents. This suggests that, unlike mammals, in certain circumstances maternal and paternal irradiation may be equally important. This study also showed that trout can induce a bystander effect 2 generations after irradiation, which further emphasises the importance of the bystander effect in aquatic radiobiology. Given the complex community structure in aquatic ecosystems, these results may have significant implications for environmental radiological protection. Copyright © 2015 Elsevier Inc. All rights reserved.

Child is father of the man: child abuse and development of future psychopathology.

Science.gov (United States)

Lecic-Tosevski, D; Draganic-Gajic, S; Pejovic-Milovancevic, M; Popovic-Deusic, S; Christodoulou, N; Botbol, M

2014-01-01

Available epidemiological data indicate that the abuse of children within families is a very common phenomenon, and is still on the rise. Among others, abuse includes direct physical and emotional violence to the child, as well as the indirect emotional trauma of witnessing interparental violence. These early trauma experienced within the context of the family can influence the development of the child's personality as well as predispose towards the development of mental disorders in adulthood. There are some important factors influencing the occurrence of abuse, or the conditions predisposing it: certain parental personality traits appear to be instrumental, and the presence of individual psychopathology of parents is also connected with different forms of family dysfunction as a system, representing a variable which is interpolated in the quality of parenthood as the most important factor that determines long-term consequences on children and possible future psychopathology. The complex but tangible effects of parents' personality traits on the psychological development of children may contribute to the transgenerational transmission of abuse and violence. The phenomenon of domestic violence and abuse can be described from the perspective of the psychological and systemic theoretical postulates. According to systemic theory and practice, dysfunctional communication in the family is a significant predictor for domestic violence. Characteristics of dysfunctional communication include low levels of verbal expressiveness and emotional responsiveness, low tolerance to criticism and its interpretation as a threat or intimidation, and consequently increased anxiety and subsequent escalation of an argument into violence. Overall it seems that there may be a complex connection between parental personality and family interaction patterns, leading to dysfunctional communication which further amplifies the detrimental characteristics of family dynamics, and eventually

Subject-Author Index 989..1009

Indian Academy of Sciences (India)

Volume 38 2013. SUBJECT INDEX. 16S rRNA .... reticulum stress-induced neuronal death in rat brain after status ... of intestinal contraction and body size in rodents and rabbits. 391. Brain ...... Trans-generational immune memory. Plant innate ...

Dynamics of radioecological and genetic processes in populations of mammalian model species at contamination of ecosystems

International Nuclear Information System (INIS)

Ryabokon', N.I.; Goncharova, R.I.

2008-01-01

A short review of data on the time course of radiobiological and genetic processes in natural populations of mammalian model species inhabiting radiocontaminated ecosystems over many generations is presented here. The described time-courses of biological end-points in these populations do not reflect the time course of the whole-body dose rates, but do the outcome of multiple processes, including the direct response to individual irradiation, the transgeneration transmission and accumulation of induced damages and the development of adaptation. (authors)

Trans-generational plasticity in physiological thermal tolerance is modulated by maternal pre-reproductive environment in the polychaete Ophryotrocha labronica.

Science.gov (United States)

Massamba-N'Siala, Gloria; Prevedelli, Daniela; Simonini, Roberto

2014-06-01

Maternal temperature is known to affect many aspects of offspring phenotype, but its effect on offspring physiological thermal tolerance has received less attention, despite the importance of physiological traits in defining organismal ability to cope with temperature changes. To fill this gap, we used the marine polychaete Ophryotrocha labronica to investigate the influence of maternal temperature on offspring upper and lower thermal tolerance limits, and assess whether maternal influence changed according to the stage of offspring pre-zygotic development at which a thermal cue was provided. Measurements were taken on adult offspring acclimated to 18 or 30°C, produced by mothers previously reared at 24°C and then exposed to 18 or 30°C at an early and late stage of oogenesis. When the shift from 24°C was provided early during oogenesis, mothers produced offspring with greater cold and heat tolerance whenever mother-offspring temperatures did not match, with respect to when they matched, suggesting the presence of an anticipatory maternal effect triggered by the thermal variation. Conversely, when the cue was provided later during oogenesis, more tolerant offspring were observed when temperatures persisted across generations. In this case, maternal exposure to 18 or 30°C may have benefited offspring performance, while limitations in the transmission of the thermal cue may account for the lack of correlation between maternal experiences and offspring performance when mother-offspring environments did not match. Our results provided evidence for a trans-generational effect of temperature on physiological performance characterised by a high context dependency, and are discussed in the light of maternal pre-reproductive experiences. © 2014. Published by The Company of Biologists Ltd.

Social enrichment during postnatal development induces transgenerational effects on emotional and reproductive behavior in mice

Directory of Open Access Journals (Sweden)

James P Curley

2009-09-01

Full Text Available Across species there is evidence that the quality of the early social environment can have a profound impact on neurobiology and behavior. In the present study we explore the effect of communal rearing conditions (3 dams with 3 litters per cage during the postnatal period on offspring (F1 and grand-offspring (F2 anxiety-like and maternal behavior in Balb/c mice. Females rearing pups in communal nests exhibited increased levels of postpartum maternal care and communal rearing was found to abolish sex-differences in weaning weights. In adulthood, communally reared offspring were observed to display reduced anxiety-like behavior when placed in a novel environment. When rearing their own offspring under standard conditions, communally reared females demonstrated higher levels of motivation to retrieve pups, built higher quality nests, and exhibited higher levels of postpartum care compared to standard reared females. When exposed to an intruder male, communally reared females were more subordinate and less aggressive. F2 offspring of communally reared females were observed to engage in reduced anxiety-like behavior, have larger litter sizes and an increased frequency of nursing on day PND 1. Analysis of neuropeptide receptor levels suggest that a communal rearing environment may exert sustained effects on behavior through modification of oxytocin and vasopressin (V1a receptor densities. Though Balb-C mice are often considered “socially-incompetent” and high in anxiety-like behavior, our findings suggest that through enrichment of the postnatal environment, these behavioral and neuroendocrine deficits may be attenuated both within and across generations.

Realizing the Potential of Adolescence to Prevent Transgenerational Conditioning of Noncommunicable Disease Risk: Multi-Sectoral Design Frameworks

Directory of Open Access Journals (Sweden)

Jacquie L. Bay

2016-07-01

Full Text Available Evidence from the field of Developmental Origins of Health and Disease (DOHaD demonstrates that early life environmental exposures impact later-life risk of non-communicable diseases (NCDs. This has revealed the transgenerational nature of NCD risk, thus demonstrating that interventions to improve environmental exposures during early life offer important potential for primary prevention of DOHaD-related NCDs. Based on this evidence, the prospect of multi-sectoral approaches to enable primary NCD risk reduction has been highlighted in major international reports. It is agreed that pregnancy, lactation and early childhood offer significant intervention opportunities. However, the importance of interventions that establish positive behaviors impacting nutritional and non-nutritional environmental exposures in the pre-conceptual period in both males and females, thus capturing the full potential of DOHaD, must not be overlooked. Adolescence, a period where life-long health-related behaviors are established, is therefore an important life-stage for DOHaD-informed intervention. DOHaD evidence underpinning this potential is well documented. However, there is a gap in the literature with respect to combined application of theoretical evidence from science, education and public health to inform intervention design. This paper addresses this gap, presenting a review of evidence informing theoretical frameworks for adolescent DOHaD interventions that is accessible collectively to all relevant sectors.

Transgenerational variations in DNA methylation induced by drought stress in two rice varieties with distinguished difference to drought resistance.

Directory of Open Access Journals (Sweden)

Xiaoguo Zheng

Full Text Available Adverse environmental conditions have large impacts on plant growth and crop production. One of the crucial mechanisms that plants use in variable and stressful natural environments is gene expression modulation through epigenetic modification. In this study, two rice varieties with different drought resistance levels were cultivated under drought stress from tilling stage to seed filling stage for six successive generations. The variations in DNA methylation of the original generation (G0 and the sixth generation (G6 of these two varieties in normal condition (CK and under drought stress (DT at seedling stage were assessed by using Methylation Sensitive Amplification Polymorphism (MSAP method. The results revealed that drought stress had a cumulative effect on the DNA methylation pattern of both varieties, but these two varieties had different responses to drought stress in DNA methylation. The DNA methylation levels of II-32B (sensitive and Huhan-3 (resistant were around 39% and 32%, respectively. Genome-wide DNA methylation variations among generations or treatments accounted for around 13.1% of total MSAP loci in II-32B, but was only approximately 1.3% in Huhan-3. In II-32B, 27.6% of total differentially methylated loci (DML were directly induced by drought stress and 3.2% of total DML stably transmitted their changed DNA methylation status to the next generation. In Huhan-3, the numbers were 48.8% and 29.8%, respectively. Therefore, entrainment had greater effect on Huhan-3 than on II-32B. Sequence analysis revealed that the DML were widely distributed on all 12 rice chromosomes and that it mainly occurred on the gene's promoter and exon region. Some genes with DML respond to environmental stresses. The inheritance of epigenetic variations induced by drought stress may provide a new way to develop drought resistant rice varieties.

Dietary-induced hyperthyroidism marginally affects neonatal testicular development

NARCIS (Netherlands)

Rijntjes, Eddy; Wientjes, Anna T.; Swarts, Hans J. M.; de Rooij, Dirk G.; Teerds, Katja J.

2008-01-01

The objective of this study was to determine whether dietary-induced mild fetal/neonatal hyperthyroidism influenced the initiation of spermatogenesis and the development of the adult-type Leydig cell population. Previously, the effects of neonatally induced hyperthyroidism have been investigated in

A Virus-Induced Assay for Functional Dissection and Analysis of Monocot and Dicot Flowering Time Genes.

Science.gov (United States)

Qin, Cheng; Chen, Weiwei; Shen, Jiajia; Cheng, Linming; Akande, Femi; Zhang, Ke; Yuan, Chen; Li, Chunyang; Zhang, Pengcheng; Shi, Nongnong; Cheng, Qi; Liu, Yule; Jackson, Stephen; Hong, Yiguo

2017-06-01

Virus-induced flowering (VIF) uses virus vectors to express Flowering Locus T ( FT ) to induce flowering in plants. This approach has recently attracted wide interest for its practical applications in accelerating breeding in crops and woody fruit trees. However, the insight into VIF and its potential as a powerful tool for dissecting florigenic proteins remained to be elucidated. Here, we describe the mechanism and further applications of Potato virus X (PVX)-based VIF in the short-day Nicotiana tabacum cultivar Maryland Mammoth. Ectopic delivery of Arabidopsis ( Arabidopsis thaliana ) AtFT by PVX/AtFT did not induce the expression of the endogenous FT ortholog NtFT4 ; however, it was sufficient to trigger flowering in Maryland Mammoth plants grown under noninductive long-day conditions. Infected tobacco plants developed no systemic symptoms, and the PVX-based VIF did not cause transgenerational flowering. We showed that the PVX-based VIF is a much more rapid method to examine the impacts of single amino acid mutations on AtFT for floral induction than making individual transgenic Arabidopsis lines for each mutation. We also used the PVX-based VIF to demonstrate that adding a His- or FLAG-tag to the N or C terminus of AtFT could affect its florigenic activity and that this system can be applied to assay the function of FT genes from heterologous species, including tomato ( Solanum lycopersicum ) SFT and rice ( Oryza sativa ) Hd3a Thus, the PVX-based VIF represents a simple and efficient system to identify individual amino acids that are essential for FT-mediated floral induction and to test the ability of mono- and dicotyledonous FT genes and FT fusion proteins to induce flowering. © 2017 American Society of Plant Biologists. All Rights Reserved.

Intergenerational epigenetic inheritance in reef-building corals

KAUST Repository

Liew, Yi Jin

2018-02-22

The notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants and metazoans. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals). Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

Intergenerational epigenetic inheritance in reef-building corals

KAUST Repository

Liew, Yi Jin; Howells, Emily J.; Wang, Xin; Michell, Craig; Burt, John A.; Idaghdour, Youssef; Aranda, Manuel

2018-01-01

The notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants and metazoans. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals). Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

Programming of stress pathways: A transgenerational perspective.

Science.gov (United States)

Constantinof, Andrea; Moisiadis, Vasilis G; Matthews, Stephen G

2016-06-01

The embryo and fetus are highly responsive to the gestational environment. Glucocorticoids (GC) represent an important class of developmental cues and are crucial for normal brain development. Levels of GC in the fetal circulation are tightly regulated. They are maintained at low levels during pregnancy, and increase rapidly at the end of gestation. This surge in GC is critical for maturation of the organs, specifically the lungs, brain and kidney. There are extensive changes in brain epigenetic profiles that accompany the GC surge, suggesting that GC may drive regulation of gene transcription through altered epigenetic pathways. The epigenetic profiles produced by the GC surge can be prematurely induced as a result of maternal or fetal stress, as well as through exposure to synthetic glucocorticoids (sGC). This is highly clinically relevant as 10% of pregnant women are at risk for preterm labour and receive treatment with sGC to promote lung development in the fetus. Fetal overexposure to GC (including sGC) has been shown to cause lasting changes in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis leading to altered stress responses, and mood and anxiety disorders in humans and animals. In animal models, GC exposure is associated with transcriptomic and epigenomic changes that influence behaviour, HPA function and growth. Importantly, programming by GC results in sex-specific effects that can be inherited over multiple generations via paternal and maternal transmission. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of inducer-free expression plasmids based on IPTG-inducible promoters for Bacillus subtilis.

Science.gov (United States)

Tran, Dinh Thi Minh; Phan, Trang Thi Phuong; Huynh, Thanh Kieu; Dang, Ngan Thi Kim; Huynh, Phuong Thi Kim; Nguyen, Tri Minh; Truong, Tuom Thi Tinh; Tran, Thuoc Linh; Schumann, Wolfgang; Nguyen, Hoang Duc

2017-07-25

Besides Escherichia coli, Bacillus subtilis is an important bacterial species for the production of recombinant proteins. Recombinant genes are inserted into shuttle expression vectors which replicate in both E. coli and in B. subtilis. The ligation products are first transformed into E. coli cells, analyzed for correct insertions, and the correct recombinant plasmids are then transformed into B. subtilis. A major problem using E. coli cells can be the strong basal level of expression of the recombinant protein which may interfere with the stability of the cells. To minimize this problem, we developed strong expression vectors being repressed in E. coli and inducer-free in B. subtilis. In general, induction of IPTG-inducible expression vectors is determined by the regulatory lacI gene encoding the LacI repressor in combination with the lacO operator on the promoter. To investigate the inducer-free properties of the vectors, we constructed inducer-free expression plasmids by removing the lacI gene and characterized their properties. First, we examined the ability to repress a reporter gene in E. coli, which is a prominent property facilitating the construction of the expression vectors carrying a target gene. The β-galactosidase (bgaB gene) basal levels expressed from Pgrac01-bgaB could be repressed at least twice in the E. coli cloning strain. Second, the inducer-free production of BgaB from four different plasmids with the Pgrac01 promoter in B. subtilis was investigated. As expected, BgaB expression levels of inducer-free constructs are at least 37 times higher than that of the inducible constructs in the absence of IPTG, and comparable to those in the presence of the inducer. Third, using efficient IPTG-inducible expression vectors containing the strong promoter Pgrac100, we could convert them into inducer-free expression plasmids. The BgaB production levels from the inducer-free plasmid in the absence of the inducer were at least 4.5 times higher than that of

Effects of germination season on life history traits and on transgenerational plasticity in seed dormancy in a cold desert annual.

Science.gov (United States)

Lu, Juan J; Tan, Dun Y; Baskin, Carol C; Baskin, Jerry M

2016-04-27

The maternal environment can influence the intensity of seed dormancy and thus seasonal germination timing and post-germination life history traits. We tested the hypotheses that germination season influences phenotypic expression of post-germination life history traits in the cold desert annual Isatis violascens and that plants from autumn- and spring-germinating seeds produce different proportions of seeds with nondeep and intermediate physiological dormancy (PD). Seeds were sown in summer and flexibility in various life history traits determined for plants that germinated in autumn and in spring. A higher percentage of spring- than of autumn-germinating plants survived the seedling stage, and all surviving plants reproduced. Number of silicles increased with plant size (autumn- > spring-germinating plants), whereas percent dry mass allocated to reproduction was higher in spring- than in autumn-germinating plants. Autumn-germinating plants produced proportionally more seeds with intermediate PD than spring-germinating plants, while spring-germinating plants produced proportionally more seeds with nondeep PD than autumn-germinating plants. Flexibility throughout the life history and transgenerational plasticity in seed dormancy are adaptations of I. violascens to its desert habitat. Our study is the first to demonstrate that autumn- and spring-germinating plants in a species population differ in proportion of seeds produced with different levels of PD.

The influence of DNA sequence on epigenome-induced pathologies

OpenAIRE

Meagher, Richard B; Müssar, Kristofer J

2012-01-01

Abstract Clear cause-and-effect relationships are commonly established between genotype and the inherited risk of acquiring human and plant diseases and aberrant phenotypes. By contrast, few such cause-and-effect relationships are established linking a chromatin structure (that is, the epitype) with the transgenerational risk of acquiring a disease or abnormal phenotype. It is not entirely clear how epitypes are inherited from parent to offspring as populations evolve, even though epigenetics...

Involvement of activation-induced cytidine deaminase in skin cancer development.

Science.gov (United States)

Nonaka, Taichiro; Toda, Yoshinobu; Hiai, Hiroshi; Uemura, Munehiro; Nakamura, Motonobu; Yamamoto, Norio; Asato, Ryo; Hattori, Yukari; Bessho, Kazuhisa; Minato, Nagahiro; Kinoshita, Kazuo

2016-04-01

Most skin cancers develop as the result of UV light-induced DNA damage; however, a substantial number of cases appear to occur independently of UV damage. A causal link between UV-independent skin cancers and chronic inflammation has been suspected, although the precise mechanism underlying this association is unclear. Here, we have proposed that activation-induced cytidine deaminase (AID, encoded by AICDA) links chronic inflammation and skin cancer. We demonstrated that Tg mice expressing AID in the skin spontaneously developed skin squamous cell carcinoma with Hras and Trp53 mutations. Furthermore, genetic deletion of Aicda reduced tumor incidence in a murine model of chemical-induced skin carcinogenesis. AID was expressed in human primary keratinocytes in an inflammatory stimulus-dependent manner and was detectable in human skin cancers. Together, the results of this study indicate that inflammation-induced AID expression promotes skin cancer development independently of UV damage and suggest AID as a potential target for skin cancer therapeutics.

The Three Gorges: the unexamined toll of development-induced displacement

Directory of Open Access Journals (Sweden)

Martin Stein

1998-04-01

Full Text Available In China, the context of forced displacement in its broadest sense centres on four issues: (1 coercive displacement for development; (2 political persecution resulting in controlled displacement; (3 massive labour dislocations; and (4 disaster-induced displacement. This article looks at the role of the state in displacement, focusing on the first of these issues: development-induced displacement.

Phenotypic effects of salt and heat stress over three generations in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Léonie Suter

Full Text Available Current and predicted environmental change will force many organisms to adapt to novel conditions, especially sessile organisms such as plants. It is therefore important to better understand how plants react to environmental stress and to what extent genotypes differ in such responses. It has been proposed that adaptation to novel conditions could be facilitated by heritable epigenetic changes induced by environmental stress, independent of genetic variation. Here we assessed phenotypic effects of heat and salt stress within and across three generations using four highly inbred Arabidopsis thaliana genotypes (Col, Cvi, Ler and Sha. Salt stress generally decreased fitness, but genotypes were differently affected, suggesting that susceptibility of A. thaliana to salt stress varies among genotypes. Heat stress at an early rosette stage had less detrimental effects but accelerated flowering in three out of four accessions. Additionally, we found three different modes of transgenerational effects on phenotypes, all harboring the potential of being adaptive: heat stress in previous generations induced faster rosette growth in Sha, both under heat and control conditions, resembling a tracking response, while in Cvi, the phenotypic variance of several traits increased, resembling diversified bet-hedging. Salt stress experienced in earlier generations altered plant architecture of Sha under salt but not control conditions, similar to transgenerational phenotypic plasticity. However, transgenerational phenotypic effects depended on the type of stress as well as on genotype, suggesting that such effects may not be a general response leading to adaptation to novel environmental conditions in A. thaliana.

Transgenerational inheritance of susceptibility to diabetes-induced male subfertility

Czech Academy of Sciences Publication Activity Database

Pavlínková, Gabriela; Margaryan, Hasmik; Žatecká, Eva; Valášková, Eliška; Elzeinová, Fatima; Kubátová, Alena; Bohuslavová, Romana; Pěknicová, Jana

2017-01-01

Roč. 7, JUL 10 2017 (2017), č. článku 4940. ISSN 2045-2322 R&D Projects: GA MZd(CZ) NV15-30880A; GA ČR(CZ) GA16-06825S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : HIGH-FAT DIET * MALE-INFERTILITY * GENE-EXPRESSION * SPERM PARAMETERS Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 4.259, year: 2016

Transgenerational effects of maternal care interact with fetal growth and influence attention skills at 18 months of age.

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Neuwald, Marla F; Agranonik, Marilyn; Portella, André K; Fleming, Alison; Wazana, Ashley; Steiner, Meir; Levitan, Robert D; Meaney, Michael J; Silveira, Patrícia P

2014-05-01

Evidence suggests that there is an association between being born small for gestational age (SGA) and an increased risk of internalizing and externalizing problems, such as ADHD. Additionally, individuals who report having received a lower quality of maternal care show an increased prevalence of depression and anxiety, and they are generally worse caregivers of their offspring. Therefore, an interaction between the birth weight status and the quality of maternal care perceived by the mother could affect behavioral outcomes of the children. Evaluate the influence of being born SGA and parental bonding, as perceived by the mother during her infancy, on the children's behavior at 18 months of age. Nested cross-sectional study within a Canadian prenatal cohort (MAVAN, Maternal Adversity, Vulnerability and Neurodevelopment) recruited from 2003 to 2010. Data from 305 children who were evaluated at 18 months of age. Early Childhood Behavior Questionnaire--ECBQ and Infant-Toddler Social and Emotional Assessment--ITSEA) were included. Children born SGA whose mothers reported low maternal care during her infancy (using the Parental Bonding Instrument--PBI) showed lower scores in the attentional set shifting trait (ECBQ, p=0.002) and attention construct (ITSEA, p=0.05) at 18 months of age. We also found that SGA increases decreases cuddliness (p=0.011) and poor perceived maternal care decreases low intensity pleasure (p=0.016) on the ECBQ. These findings suggest a complex transgenerational transmission whereby mother's own care interacts with the fetal growth of her offspring to predict its attentional skills at 18 months of age. Copyright © 2014 Elsevier Ltd. All rights reserved.

Developing better mouse models to study cisplatin-induced kidney injury.

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Sharp, Cierra N; Siskind, Leah J

2017-10-01

Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer. However, its dose-limiting side effect is nephrotoxicity leading to acute kidney injury (AKI). Patients who develop AKI have an increased risk of mortality and are more likely to develop chronic kidney disease (CKD). Unfortunately, there are no therapeutic interventions for the treatment of AKI. It has been suggested that the lack of therapies is due in part to the fact that the established mouse model used to study cisplatin-induced AKI does not recapitulate the cisplatin dosing regimen patients receive. In recent years, work has been done to develop more clinically relevant models of cisplatin-induced kidney injury, with much work focusing on incorporation of multiple low doses of cisplatin administered over a period of weeks. These models can be used to recapitulate the development of CKD after AKI and, by doing so, increase the likelihood of identifying novel therapeutic targets for the treatment of cisplatin-induced kidney injury. Copyright © 2017 the American Physiological Society.

Development of a flood-induced health risk prediction model for Africa

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Lee, D.; Block, P. J.

2017-12-01

Globally, many floods occur in developing or tropical regions where the impact on public health is substantial, including death and injury, drinking water, endemic disease, and so on. Although these flood impacts on public health have been investigated, integrated management of floods and flood-induced health risks is technically and institutionally limited. Specifically, while the use of climatic and hydrologic forecasts for disaster management has been highlighted, analogous predictions for forecasting the magnitude and impact of health risks are lacking, as is the infrastructure for health early warning systems, particularly in developing countries. In this study, we develop flood-induced health risk prediction model for African regions using season-ahead flood predictions with climate drivers and a variety of physical and socio-economic information, such as local hazard, exposure, resilience, and health vulnerability indicators. Skillful prediction of flood and flood-induced health risks can contribute to practical pre- and post-disaster responses in both local- and global-scales, and may eventually be integrated into multi-hazard early warning systems for informed advanced planning and management. This is especially attractive for areas with limited observations and/or little capacity to develop flood-induced health risk warning systems.

Development of a collision induced dissociation ion cyclotron resonance spectrometer

International Nuclear Information System (INIS)

Fan, Y.N.

1982-01-01

A transient analysis ion cyclotron resonance spectrometer is developed to investigate the phenomena of collision induced dissociation. The Fourier transform method and the modified maximum entropy spectral analysis or covariance least square method are implemented in measuring the mass spectrum of the ion ensemble. The Fourier transform method can be used in quantitative analysis while the maximum entropy method as developed here is useful for qualitative analysis only. The cyclotron resonance frequency, relaxation time constant, and the relative ion population are observable from the Fourier transform spectrum. These parameters are very important in investigating collision induced dissociation process and other topics in gas phase chemistry. The ion cyclotron resonance spectrometer is not only developed to study fragments and their abundance from a parent ion, but also to determine the threshold energy and reaction cross section in the collision induced dissociation process. When hard sphere model is used in the ion-molecule collision, the radius of acetone ion measured from the reactive cross section is 2.2 angstrom which is very close to the physical dimension of acetone. The threshold energy for acetone ion in collision induced dissociation process is 1.8 eV which is similar to the result obtained by the angle-resolved mass spectrometer

Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism.

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Cowin, Prue A; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K; Foster, Paul M D; Scott, Hamish S; Risbridger, Gail P

2010-02-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-kappaB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-kappaB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression.

Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain

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Mariko Saito

2016-08-01

Full Text Available Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD. While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy. Previous literature indicates that acute binge-like ethanol exposure in postnatal day 7 (P7 mice induces apoptotic neurodegeneration, transient activation of microglia resulting in phagocytosis of degenerating neurons, and a prolonged increase in glial fibrillary acidic protein-positive astrocytes. In our present study, systemic administration of a moderate dose of lipopolysaccharides, which causes glial activation, attenuates ethanol-induced neurodegeneration. These studies suggest that activation of microglia and astrocytes by acute ethanol in the neonatal brain may provide neuroprotection. However, repeated or chronic ethanol can induce significant proinflammatory glial reaction and neurotoxicity. Further studies are necessary to elucidate whether acute or sustained glial activation caused by ethanol exposure in the developing brain can affect long-lasting cellular and behavioral abnormalities observed in the adult brain.

Maternal antioxidant provisioning mitigates pollutant-induced oxidative damage in embryos of the temperate sea urchin Evechinus chloroticus

OpenAIRE

Lister, Kathryn N.; Lamare, Miles D.; Burritt, David J.

2017-01-01

One mechanism of pollution resistance in marine populations is through transgenerational plasticity, whereby offspring capacity to resist pollution reflects parental exposure history. Our study aimed to establish correlations between oxidative stress biomarkers and key reproductive fitness parameters in the temperate sea urchin Evechinus chloroticus following exposure to dietary polycyclic aromatic hydrocarbons (PAHs). PAH-exposed adults exhibited total gonad tissue concentrations of PAHs in ...

Heparanase-1 activities in the development of laser induced choroidal neovascularization

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Bao-Ke Hou

2013-04-01

Full Text Available AIM:To investigate the role of heparanase-1 in laser-induced choroidal neovascularization (CNV.METHODS:Experimental CNV was induced by krypton laser photocoagulation in 15 male Brown Norway rats. Fundus fluorescein angiography and histopathological examination were performed in observing the CNV development. The expression and distribution of heparanase-1 protein in the laser lesions were determined by immunohistochemistry and western blotting analysis.RESULTS:The success rate of laser induced CNV was approximately 75% on 3-4 weeks after laser photocoagulation. The protein levels of heparanase-1 increased significantly in the retina-choroidal complex of CNV models when compared to normal rat eyes (P<0.01. Immunostaining confirmed strong heparanase-1 expressions in all laser lesions, and it displayed to be highest at the newly formed blood vessels within the fibrovascular complex in the subretinal space.CONCLUSION:Heparanase-1 is closely involved in the development of laser induced CNV.

Attenuation of a radiation-induced conditioned taste aversion after the development of ethanol tolerance

International Nuclear Information System (INIS)

Hunt, W.A.; Rabin, B.M.

1988-01-01

An attempt to reduce a radiation-induced conditioned taste aversion (CTA) was undertaken by rendering animals tolerant to ethanol. Ethanol tolerance, developed over 5 days, was sufficient to block a radiation-induced taste aversion, as well as an ethanol-induced CTA. Several intermittent doses of ethanol, which did not induce tolerance but removed the novelty of the conditioning stimulus, blocked an ethanol-induced CTA but not the radiation-induced CTA. A CTA induced by doses of radiation up to 500 rads was attenuated. These data suggest that radioprotection developing in association with ethanol tolerance is a result of a physiological response to the chronic presence of ethanol not to the ethanol itself

Public perceptions and acceptance of induced earthquakes related to energy development

International Nuclear Information System (INIS)

McComas, Katherine A.; Lu, Hang; Keranen, Katie M.; Furtney, Maria A.; Song, Hwansuck

2016-01-01

Growing awareness of the potential for some energy-related activities to induce earthquakes has created a need to understand how the public evaluates the risks of induced earthquakes versus the benefits of energy development. To address this need, this study presents a web survey that used a between-subjects factorial experimental design to explore the views of 325 U.S. adults, who were asked about their experiences with earthquakes; risk perceptions related to different causes of earthquakes (e.g., natural versus induced); and acceptability of earthquakes depending on the benefits, beneficiaries, and decision making process. The results found that participants had more negative feelings toward induced versus naturally occurring earthquakes. Although they judged no earthquake as “acceptable,” participants rated induced earthquakes significantly less acceptable than naturally occurring ones. Attributing the benefits to the provision of renewable energy or climate change mitigation did not increase induced earthquake acceptability, and no particular beneficiary made earthquakes more acceptable, although private companies as beneficiaries made earthquakes less acceptable. Finally, induced earthquake acceptability was significantly higher when people believed that people like them had a voice in the decision to implement the technology that caused the earthquake, underscoring the importance of public engagement in the development of energy technologies. - Highlights: • Human induced earthquakes were perceived as more negative than natural earthquakes. • Attributing benefits to renewable energy did not increase earthquake acceptability. • Acceptability was highest after a procedurally fair decision making process. • Acceptability was lowest following an expert-driven decision.

Influence of radiation-induced apoptosis on development brain in molecular regulation

International Nuclear Information System (INIS)

Gu Guixiong

2000-01-01

An outline of current status on the influence of radiation on the development brain was given. Some genes as immediate early gene, Bcl-2 family, p53, heat shock protein and AT gene play an important regulation role in ionizing radiation-induced development brain cells apoptosis. And such biological factor as nerve growth factor, interleukin-1, tumor necrosis factor, basic fibroblast growth factor, transforming growth factor and so on have a vital protection function against ionizing radiation-induced cells apoptosis

Sex-biased terminal investment in offspring induced by maternal immune challenge in the house wren (Troglodytes aedon).

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Bowers, E Keith; Smith, Rebecca A; Hodges, Christine J; Zimmerman, Laura M; Thompson, Charles F; Sakaluk, Scott K

2012-07-22

The reproductive costs associated with the upregulation of immunity have been well-documented and constitute a fundamental trade-off between reproduction and self-maintenance. However, recent experimental work suggests that parents may increase their reproductive effort following immunostimulation as a form of terminal parental investment as prospects for future reproduction decline. We tested the trade-off and terminal investment hypotheses in a wild population of house wrens (Troglodytes aedon) by challenging the immune system of breeding females with lipopolysaccharide, a potent but non-lethal antigen. Immunized females showed no evidence of reproductive costs; instead, they produced offspring of higher phenotypic quality, but in a sex-specific manner. Relative to control offspring, sons of immunized females had increased body mass and their sisters exhibited higher cutaneous immune responsiveness to phytohaemagglutinin injection, constituting an adaptive strategy of sex-biased allocation by immune-challenged females to enhance the reproductive value of their offspring. Thus, our results are consistent with the terminal investment hypothesis, and suggest that maternal immunization can induce pronounced transgenerational effects on offspring phenotypes.

Development-induced Displacement and Sustainable Development. The Case Study of Slezská Harta Dam in the Czech Republic

Czech Academy of Sciences Publication Activity Database

Cahlíková, Zuzana; Stojanov, Robert

2013-01-01

Roč. 8, č. 2 (2013), s. 75-84 ISSN 1895-6912 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073; GA MŠk(CZ) LD13032; GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : development -induced displacement * sustainable development * Czech Republic * Slezská Harta Dam * environmentally induced migration Subject RIV: AO - Sociology, Demography Impact factor: 1.510, year: 2013

Tunicamycin-induced unfolded protein response in the developing mouse brain

International Nuclear Information System (INIS)

Wang, Haiping; Wang, Xin; Ke, Zun-Ji; Comer, Ashley L.; Xu, Mei; Frank, Jacqueline A.; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

2015-01-01

Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific

Tunicamycin-induced unfolded protein response in the developing mouse brain

Energy Technology Data Exchange (ETDEWEB)

Wang, Haiping; Wang, Xin [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-Ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203 (China); Comer, Ashley L.; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Zhang, Zhuo; Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States)

2015-03-15

Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific.

Transgenerational effects of the endocrine disruptor vinclozolin on the methylation pattern of imprinted genes in the mouse sperm.

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Stouder, Christelle; Paoloni-Giacobino, Ariane

2010-02-01

Endocrine-disrupting chemicals (EDCs), among which is the antiandrogen vinclozolin (VCZ), have been reported to affect the male reproductive system. In this study, VCZ was administered to pregnant mice at the time of embryo sex determination, and its possible effects on the differentially methylated domains (DMDs) of two paternally (H19 and Gtl2) and three maternally (Peg1, Snrpn, and Peg3) imprinted genes were tested in the male offspring. The CpGs methylation status within the five gene DMDs was analyzed in the sperm, tail, liver, and skeletal muscle DNAs by pyrosequencing. In the sperm of controls, the percentages of methylated CpGs were close to the theoretical values of 100 and 0% in paternally or maternally imprinted genes respectively. VCZ decreased the percentages of methylated CpGs of H19 and Gtl2 (respective values 83.1 and 91.5%) and increased those of Peg1, Snrpn, and Peg3 (respective values 11.3, 18.3, and 11.2%). The effects of VCZ were transgenerational, but they disappeared gradually from F1 to F3. The mean sperm concentration of the VCZ-administered female offspring was only 56% of that of the controls in the F1 offspring, and it was back to normal values in the F2 and F3 offspring. In the somatic cells of controls, the percentages of methylated CpGs were close to the theoretical value of 50% and, surprisingly, VCZ altered the methylation of Peg3. We propose that the deleterious effects of VCZ on the male reproductive system are mediated by imprinting defects in the sperm. The reported effects of EDCs on human male spermatogenesis might be mediated by analogous imprinting alterations.

Development of a tensile-stress-induced anisotropy in amorphous magnetic thin films

International Nuclear Information System (INIS)

Mandal, K.; Vazquez, M.; Garcia, D.; Castano, F.J.; Prados, C.; Hernando, A.

2000-01-01

Magnetic anisotropy was induced in positive magnetostrictive Fe 80 B 20 and negative magnetostrictive Co 75 Si 15 B 10 thin films by developing a tensile stress within the samples. The films were grown on the concave surfaces of mechanically bowed glass substrates. On releasing the substrates from the substrate holders, a tensile stress was developed within the samples that modified the domain structure. As a result of it, a magnetic easy axis parallel to the direction of the stress was induced in FeB sample whereas in CoSiB sample the induced easy axis was perpendicular to the direction of the developed stress. To produce magnetic multilayers with crossed anisotropy, FeB/CoSiB bilayers and FeB/Cu/CoSiB trilayers were grown on bowed substrates. The study of magnetic properties of the multilayers indicates the development of crossed anisotropy within them, particularly when the magnetic layers are separated by a nonmagnetic Cu layer

Endotoxin induced chorioamnionitis prevents intestinal development during gestation in fetal sheep.

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Tim G A M Wolfs

Full Text Available Chorioamnionitis is the most significant source of prenatal inflammation and preterm delivery. Prematurity and prenatal inflammation are associated with compromised postnatal developmental outcomes, of the intestinal immune defence, gut barrier function and the vascular system. We developed a sheep model to study how the antenatal development of the gut was affected by gestation and/or by endotoxin induced chorioamnionitis.Chorioamnionitis was induced at different gestational ages (GA. Animals were sacrificed at low GA after 2d or 14d exposure to chorioamnionitis. Long term effects of 30d exposure to chorioamnionitis were studied in near term animals after induction of chorioamnionitis. The cellular distribution of tight junction protein ZO-1 was shown to be underdeveloped at low GA whereas endotoxin induced chorioamnionitis prevented the maturation of tight junctions during later gestation. Endotoxin induced chorioamnionitis did not induce an early (2d inflammatory response in the gut in preterm animals. However, 14d after endotoxin administration preterm animals had increased numbers of T-lymphocytes, myeloperoxidase-positive cells and gammadelta T-cells which lasted till 30d after induction of chorioamnionitis in then near term animals. At early GA, low intestinal TLR-4 and MD-2 mRNA levels were detected which were further down regulated during endotoxin-induced chorioamnionitis. Predisposition to organ injury by ischemia was assessed by the vascular function of third-generation mesenteric arteries. Endotoxin-exposed animals of low GA had increased contractile response to the thromboxane A2 mimetic U46619 and reduced endothelium-dependent relaxation in responses to acetylcholine. The administration of a nitric oxide (NO donor completely restored endothelial dysfunction suggesting reduced NO bioavailability which was not due to low expression of endothelial nitric oxide synthase.Our results indicate that the distribution of the tight

Global transgenerational gene expression dynamics in two newly synthesized allohexaploid wheat (Triticum aestivum lines

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Qi Bao

2012-01-01

Full Text Available Abstract Background Alteration in gene expression resulting from allopolyploidization is a prominent feature in plants, but its spectrum and extent are not fully known. Common wheat (Triticum aestivum was formed via allohexaploidization about 10,000 years ago, and became the most important crop plant. To gain further insights into the genome-wide transcriptional dynamics associated with the onset of common wheat formation, we conducted microarray-based genome-wide gene expression analysis on two newly synthesized allohexaploid wheat lines with chromosomal stability and a genome constitution analogous to that of the present-day common wheat. Results Multi-color GISH (genomic in situ hybridization was used to identify individual plants from two nascent allohexaploid wheat lines between Triticum turgidum (2n = 4x = 28; genome BBAA and Aegilops tauschii (2n = 2x = 14; genome DD, which had a stable chromosomal constitution analogous to that of common wheat (2n = 6x = 42; genome BBAADD. Genome-wide analysis of gene expression was performed for these allohexaploid lines along with their parental plants from T. turgidum and Ae. tauschii, using the Affymetrix Gene Chip Wheat Genome-Array. Comparison with the parental plants coupled with inclusion of empirical mid-parent values (MPVs revealed that whereas the great majority of genes showed the expected parental additivity, two major patterns of alteration in gene expression in the allohexaploid lines were identified: parental dominance expression and non-additive expression. Genes involved in each of the two altered expression patterns could be classified into three distinct groups, stochastic, heritable and persistent, based on their transgenerational heritability and inter-line conservation. Strikingly, whereas both altered patterns of gene expression showed a propensity of inheritance, identity of the involved genes was highly stochastic, consistent with the involvement of diverse Gene Ontology (GO

Development of microwave-enhanced spark-induced breakdown spectroscopy

International Nuclear Information System (INIS)

Ikeda, Yuji; Moon, Ahsa; Kaneko, Masashi

2010-01-01

We propose microwave-enhanced spark-induced breakdown spectroscopy with the same measurement and analysis processes as in laser-induced breakdown spectroscopy, but with a different plasma generation mechanism. The size and lifetime of the plasma generated can contribute to increased measurement accuracy and expand its applicability to industrial measurement, such as an exhaust gas analyzer for automobile engine development and its regulation, which has been hard to operate by laser at an engineering evaluation site. The use of microwaves in this application helps lower the cost, reduce the system size, and increase the ease of operation to make it commercially viable. A microwave frequency of 2.45 GHz was used to enhance the volume and lifetime of the plasma at atmospheric condition even at elevated pressure.

DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development.

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Yosuke Ichijima

Full Text Available During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploidy/aneuploidy generation in association with mitotic aberration. Although oncogene acceleration primarily induces DNA replication stress and the resulting lesions in the S phase, these lesions are carried over into the M phase and cause cytokinesis failure and genomic instability. Unlike directly induced DNA double-strand breaks, DNA replication stress-associated lesions are cryptogenic and pass through cell-cycle checkpoints due to limited and ineffective activation of checkpoint factors. Furthermore, since damaged M-phase cells still progress in mitotic steps, these cells result in chromosomal mis-segregation, cytokinesis failure and the resulting tetraploidy generation. Thus, our results reveal a process of genomic instability generation triggered by precancerous DNA replication stress.

Limitations of polyethylene glycol-induced precipitation as predictive tool for protein solubility during formulation development.

Science.gov (United States)

Hofmann, Melanie; Winzer, Matthias; Weber, Christian; Gieseler, Henning

2018-05-01

Polyethylene glycol (PEG)-induced protein precipitation is often used to extrapolate apparent protein solubility at specific formulation compositions. The procedure was used for several fields of application such as protein crystal growth but also protein formulation development. Nevertheless, most studies focused on applicability in protein crystal growth. In contrast, this study focuses on applicability of PEG-induced precipitation during high-concentration protein formulation development. In this study, solubility of three different model proteins was investigated over a broad range of pH. Solubility values predicted by PEG-induced precipitation were compared to real solubility behaviour determined by either turbidity or content measurements. Predicted solubility by PEG-induced precipitation was confirmed for an Fc fusion protein and a monoclonal antibody. In contrast, PEG-induced precipitation failed to predict solubility of a single-domain antibody construct. Applicability of PEG-induced precipitation as indicator of protein solubility during formulation development was found to be not valid for one of three model molecules. Under certain conditions, PEG-induced protein precipitation is not valid for prediction of real protein solubility behaviour. The procedure should be used carefully as tool for formulation development, and the results obtained should be validated by additional investigations. © 2017 Royal Pharmaceutical Society.

Microbial contributions to the persistence of coral reefs.

Science.gov (United States)

Webster, Nicole S; Reusch, Thorsten B H

2017-10-01

On contemplating the adaptive capacity of reef organisms to a rapidly changing environment, the microbiome offers significant and greatly unrecognised potential. Microbial symbionts contribute to the physiology, development, immunity and behaviour of their hosts, and can respond very rapidly to changing environmental conditions, providing a powerful mechanism for acclimatisation and also possibly rapid evolution of coral reef holobionts. Environmentally acquired fluctuations in the microbiome can have significant functional consequences for the holobiont phenotype upon which selection can act. Environmentally induced changes in microbial abundance may be analogous to host gene duplication, symbiont switching / shuffling as a result of environmental change can either remove or introduce raw genetic material into the holobiont; and horizontal gene transfer can facilitate rapid evolution within microbial strains. Vertical transmission of symbionts is a key feature of many reef holobionts and this would enable environmentally acquired microbial traits to be faithfully passed to future generations, ultimately facilitating microbiome-mediated transgenerational acclimatisation (MMTA) and potentially even adaptation of reef species in a rapidly changing climate. In this commentary, we highlight the capacity and mechanisms for MMTA in reef species, propose a modified Price equation as a framework for assessing MMTA and recommend future areas of research to better understand how microorganisms contribute to the transgenerational acclimatisation of reef organisms, which is essential if we are to reliably predict the consequences of global change for reef ecosystems.

No evidence for cumulative effects in a Dnmt3b hypomorph across multiple generations

Czech Academy of Sciences Publication Activity Database

Youngson, N.A.; Epp, Trevor; Roberts, A.R.; Daxinger, L.; Ashe, A.; Huang, E.; Lester, K.L.; Harten, S.K.; Kay, G.F.; Cox, T.; Matthews, J.M.; Chong, S.; Whitelaw, E.

2013-01-01

Roč. 24, 5-6 (2013), s. 206-217 ISSN 0938-8990 Institutional support: RVO:68378050 Keywords : epigenetic inheritance * mammalian development * transgenerational Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.883, year: 2013

IL-23 Is Essential for the Development of Elastase-Induced Pulmonary Inflammation and Emphysema.

Science.gov (United States)

Fujii, Utako; Miyahara, Nobuaki; Taniguchi, Akihiko; Waseda, Koichi; Morichika, Daisuke; Kurimoto, Etsuko; Koga, Hikari; Kataoka, Mikio; Gelfand, Erwin W; Cua, Daniel J; Yoshimura, Akihiko; Tanimoto, Mitsune; Kanehiro, Arihiko

2016-11-01

We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-23 -/- ) and wild-type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-23 -/- mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage fluid of WT mice was attenuated in IL-23 -/- mice, and the reduction was associated with decreased levels of keratinocyte-derived cytokine and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23/IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.

Radiation induced effects in the developing central nervous system

International Nuclear Information System (INIS)

Gisone, P.; Dubner, D.; Michelin, S.C.; Perez, M.R. Del

1997-01-01

The embryo and the human foetus are particularly sensitive to ionizing radiation and this sensitivity presents various qualitative and quantitative functional changes during intra-uterine development. Apart from radiation induced carcinogenesis, the most serious consequence of prenatal exposure in human beings is severe mental retardation. The principal data on radiation effects on human beings in the development of the central nervous system come form epidemiological studies carried out in individuals exposed in utero during the atomic explosion at Hiroshima and Nagasaki. These observations demonstrate the existence of a time of maximum radiosensitivity between the weeks 8 and 15 of the gestational period, a period in which the proliferation and neuronal migration takes place. Determination of the characteristics of dose-response relationship and the possible existence of a threshold dose of radiation effects on the development of the central nervous system is relevant to radiation protection against low dose radiation and the establishment of dose limits for occupational exposure and the public. Studies were conducted on the generation of nitrous-oxide and its relation with the production of active species of oxygen in brains of exposed rats in utero exposed to doses of up to 1 Gy during their maximum radiosensitivity. The possible role of the mechanism of radiation induced damage in the development of the central nervous system is discussed

Development of an animal model for heavy ion radiation-induced nausea and vomiting

International Nuclear Information System (INIS)

Yamatodani, Atsushi; Yamamoto, Kouichi; Nohara, Kyoko

2003-01-01

Emesis is one of the most characteristic side effects of radiation therapy. Clinical and pharmacological findings indicate that the peripheral serotonergic pathway is predominantly involved in the development of radiation-induced emesis, but the precise etiology is still unknown. We previously demonstrated that the activation of the histaminergic neuron system in the brain is essential for the development of motion-induced emesis (motion sickness). In this study, we studied the effects of heavy-ion irradiation on the hypothalamic histamine release measured in vivo with a microdialysis method in mice. Total body irradiation at dose of 8 Gy (carbon ion: 290 MeV/u, 6 cm spread-out Bragg peak (SOBP)) did not cause any significant changes in the histamine release in mice. These findings indicate that the central histaminergic activation is not involved in the development of radiation-induced emesis in mice. (author)

dNTP deficiency induced by HU via inhibiting ribonucleotide reductase affects neural tube development

International Nuclear Information System (INIS)

Guan, Zhen; Wang, Xiuwei; Dong, Yanting; Xu, Lin; Zhu, Zhiqiang; Wang, Jianhua; Zhang, Ting; Niu, Bo

2015-01-01

Highlights: • Murine NTDs were successfully induced by means of hydroxyurea (HU). • The impairment of dNTP was induced via inhibition of ribonucleotide reductase. • dNTP deficiency induced by HU caused defective DNA synthesis and repair. • Abnormal apoptosis and proliferation induced by HU affected neural tube development. - Abstract: Exposure to environmental toxic chemicals in utero during the neural tube development period can cause developmental disorders. To evaluate the disruption of neural tube development programming, the murine neural tube defects (NTDs) model was induced by interrupting folate metabolism using methotrexate in our previous study. The present study aimed to examine the effects of dNTP deficiency induced by hydroxyurea (HU), a specific ribonucleotide reductase (RNR) inhibitor, during murine neural tube development. Pregnant C57BL/6J mice were intraperitoneally injected with various doses of HU on gestation day (GD) 7.5, and the embryos were checked on GD 11.5. RNR activity and deoxynucleoside triphosphate (dNTP) levels were measured in the optimal dose. Additionally, DNA damage was examined by comet analysis and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. Cellular behaviors in NTDs embryos were evaluated with phosphorylation of histone H3 (PH-3) and caspase-3 using immunohistochemistry and western blot analysis. The results showed that NTDs were observed mostly with HU treatment at an optimal dose of 225 mg/kg b/w. RNR activity was inhibited and dNTP levels were decreased in HU-treated embryos with NTDs. Additionally, increased DNA damage, decreased proliferation, and increased caspase-3 were significant in NTDs embryos compared to the controls. Results indicated that HU induced murine NTDs model by disturbing dNTP metabolism and further led to the abnormal cell balance between proliferation and apoptosis

Pathogen-induced maternal effects result in enhanced immune responsiveness across generations.

Science.gov (United States)

Rosengaus, Rebeca B; Hays, Nicole; Biro, Colette; Kemos, James; Zaman, Muizz; Murray, Joseph; Gezahegn, Bruck; Smith, Wendy

2017-05-01

Parental investment theory postulates that adults can accurately perceive cues from their surroundings, anticipate the needs of future offspring based on those cues, and selectively allocate nongenetic resources to their progeny. Such context-dependent parental contributions can result in phenotypically variable offspring. Consistent with these predictions, we show that bacterially exposed Manduca sexta mothers oviposited significantly more variable embryos (as measured by mass, volume, hatching time, and hatching success) relative to naïve and control mothers. By using an in vivo "clearance of infection" assay, we also show that challenged larvae born to heat-killed- or live- Serratia -injected mothers, supported lower microbial loads and cleared the infection faster than progeny of control mothers. Our data support the notion that mothers can anticipate the future pathogenic risks and immunological needs of their unborn offspring, providing progeny with enhanced immune protection likely through transgenerational immune priming. Although the inclusion of live Serratia into oocytes does not appear to be the mechanism by which mothers confer protection to their young, other mechanisms, including epigenetic modifications in the progeny due to maternal pathogenic stress, may be at play. The adaptive nature of maternal effects in the face of pathogenic stress provides insights into parental investment, resource allocation, and life-history theories and highlights the significant role that pathogen-induced maternal effects play as generators and modulators of evolutionary change.

Adolescent education: an opportunity to create a Developmental Origins of Health and Disease (DOHaD) circuit breaker.

Science.gov (United States)

Bay, J L; Vickers, M H

2016-10-01

Health before conception, and periconceptional nutritional environments, contribute to conditioning of later-life health and disease. Health behaviors developed during adolescence continue into adulthood. Thus, even when the gap between pregnancy and adolescence is substantial, behaviors developed during adolescence influence later-life non-communicable disease (NCD) vulnerability in offspring. Consequently, adolescence is an important life phase where development of positive health behaviors can contribute to disruption of transgenerational cycles of NCD risk. Schooling is a core activity during adolescence. Modern curricula focus on development of capabilities associated with critical, engaged citizenship, empowering learning that supports action-based engagement in complex issues. Contexts relevant to adolescents and their communities, such as the NCD epidemic, are used to facilitate learning. Thus, engaging the education sector as participants in the work of the Developmental Origins of Health and Disease community offers an important strategy to capture the potential of adolescence as a life stage for transgenerational primary prevention of obesity and NCD risk.

The Development of Countermeasures for Space Radiation Induced Adverse Health Effects

Science.gov (United States)

Kennedy, Ann

The Development of Countermeasures for Space Radiation Induced Adverse Health Effects Ann R. Kennedy Department of Radiation Oncology, University of Pennsylvania School of Medicine, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA, United States 19104-6072 The development of countermeasures for radiation induced adverse health effects is a lengthy process, particularly when the countermeasure/drug has not yet been evaluated in human trials. One example of a drug developed from the bench to the clinic is the soybean-derived Bowman-Birk inhibitor (BBI), which has been developed as a countermeasure for radiation induced cancer. It was originally identified as a compound/drug that could prevent the radiation induced carcinogenic process in an in vitro assay system in 1975. The first observation that BBI could inhibit carcinogenesis in animals was in 1985. BBI received Investigational New Drug (IND) Status with the U.S. Food and Drug Administration (FDA) in 1992 (after several years of negotiation with the FDA about the potential IND status of the drug), and human trials began at that time. Phase I, II and III human trials utilizing BBI have been performed under several INDs with the FDA, and an ongoing Phase III trial will be ending in the very near future. Thus, the drug has been in development for 35 years at this point, and it is still not a prescription drug on the market which is available for human use. A somewhat less time-consuming process is to evaluate compounds that are on the GRAS (Generally Recognized as Safe) list. These compounds would include some over-the-counter medications, such as antioxidant vitamins utilized in human trials at the levels for which Recommended Dietary Allowances (RDAs) have been established. To determine whether GRAS substances are able to have beneficial effects on radiation induced adverse health effects, it is still likely to be a lengthy process involving many years to potentially decades of human trial work. The

Epigenomics, gestational programming and risk of metabolic syndrome.

Science.gov (United States)

Desai, M; Jellyman, J K; Ross, M G

2015-04-01

Epigenetic mechanisms are emerging as mediators linking early environmental exposures during pregnancy with programmed changes in gene expression that alter offspring growth and development. There is irrefutable evidence from human and animal studies that nutrient and environmental agent exposures (for example, endocrine disruptors) during pregnancy may affect fetal/newborn development resulting in offspring obesity and obesity-associated metabolic abnormalities (metabolic syndrome). This concept of 'gestational programming' is associated with alterations to the epigenome (nongenomic) rather than changes in the DNA sequence (genomic). Epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling and/or regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype. Recent studies have shown tissue-specific transcriptome patterns and phenotypes not only in the exposed individual, but also in subsequent progeny. Notably, the transmission of gestational programming effects to subsequent generations occurs in the absence of continued adverse environmental exposures, thus propagating the cycle of obesity and metabolic syndrome. This phenomenon may be attributed to an extrinsic process resulting from the maternal phenotype and the associated nutrient alterations occurring within each pregnancy. In addition, epigenetic inheritance may occur through somatic cells or through the germ line involving both maternal and paternal lineages. Since epigenetic gene modifications may be reversible, understanding how epigenetic mechanisms contribute to transgenerational transmission of obesity and metabolic dysfunction is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome. In this review we discuss the evidence in human and animal studies for the role of

Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring

Directory of Open Access Journals (Sweden)

Neil A Youngson

2016-01-01

Full Text Available There is now strong evidence that the paternal contribution to offspring phenotype at fertilisation is more than just DNA. However, the identity and mechanisms of this nongenetic inheritance are poorly understood. One of the more important questions in this research area is: do changes in sperm DNA methylation have phenotypic consequences for offspring? We have previously reported that offspring of obese male rats have altered glucose metabolism compared with controls and that this effect was inherited through nongenetic means. Here, we describe investigations into sperm DNA methylation in a new cohort using the same protocol. Male rats on a high-fat diet were 30% heavier than control-fed males at the time of mating (16-19 weeks old, n = 14/14. A small (0.25% increase in total 5-methyl-2Ͳ-deoxycytidine was detected in obese rat spermatozoa by liquid chromatography tandem mass spectrometry. Examination of the repetitive fraction of the genome with methyl-CpG binding domain protein-enriched genome sequencing (MBD-Seq and pyrosequencing revealed that retrotransposon DNA methylation states in spermatozoa were not affected by obesity, but methylation at satellite repeats throughout the genome was increased. However, examination of muscle, liver, and spermatozoa from male 27-week-old offspring from obese and control fathers (both groups from n = 8 fathers revealed that normal DNA methylation levels were restored during offspring development. Furthermore, no changes were found in three genomic imprints in obese rat spermatozoa. Our findings have implications for transgenerational epigenetic reprogramming. They suggest that postfertilization mechanisms exist for normalising some environmentally-induced DNA methylation changes in sperm cells.

Protective Effect of a Mitochondria-Targeted Peptide against the Development of Chemotherapy-Induced Peripheral Neuropathy in Mice.

Science.gov (United States)

Toyama, Satoshi; Shimoyama, Naohito; Szeto, Hazel H; Schiller, Peter W; Shimoyama, Megumi

2018-04-18

Several chemotherapeutic agents used for cancer treatment induce dose-limiting peripheral neuropathy that compromises patients' quality of life and limits cancer treatment. Recently, mitochondrial dysfunction has been shown to be involved in the mechanism of chemotherapy-induced peripheral neuropathy. SS-20 is a mitochondria-targeted peptide that promotes mitochondrial respiration and restores mitochondrial bioenergetics. In the present study, we examined the protective effect of SS-20 against the development of chemotherapy-induced peripheral neuropathy utilizing a murine model of peripheral neuropathy induced by oxaliplatin, a first-line chemotherapy agent for colon cancer. Weekly administrations of oxaliplatin induced peripheral neuropathy as demonstrated by the development of neuropathic pain and loss of intraepidermal nerve fibers in the hind paw. Continuous administration of SS-20 protected against the development of oxaliplatin-induced neuropathic pain and mitigated the loss of intraepidermal nerve fibers to normal levels. Our findings suggest that SS-20 may be a drug candidate for the prevention of chemotherapy-induced peripheral neuropathy.

Reaction of somatic cells of mice and their posterity on xenobiotic in contaminated environment

International Nuclear Information System (INIS)

Konoplya, E.F.; Malenchenko, A.F.; Sushko, S.N.; Kadukova, E.M.; Savin, A.O.; Goncharov, S.V.

2008-01-01

The cycle of researches of influence of an exposition of mice of line Af in the conditions of a zone of alienation of the Chernobyl NPP on spontaneous and chemically induced mutability, lung tumour (adenomas), morphological and functional a condition of alveolar macrophages is executed. The increase in frequency polychromatic in mouse bone marrow, adenomas in lungs, and also change of sensitivity of an organism to action mutagen and transgeneration transfer of genetic damages is shown. (authors)

Ocean acidification challenges copepod phenotypic plasticity

Science.gov (United States)

Vehmaa, Anu; Almén, Anna-Karin; Brutemark, Andreas; Paul, Allanah; Riebesell, Ulf; Furuhagen, Sara; Engström-Öst, Jonna

2016-11-01

Ocean acidification is challenging phenotypic plasticity of individuals and populations. Calanoid copepods (zooplankton) are shown to be fairly plastic against altered pH conditions, and laboratory studies indicate that transgenerational effects are one mechanism behind this plasticity. We studied phenotypic plasticity of the copepod Acartia sp. in the course of a pelagic, large-volume mesocosm study that was conducted to investigate ecosystem and biogeochemical responses to ocean acidification. We measured copepod egg production rate, egg-hatching success, adult female size and adult female antioxidant capacity (ORAC) as a function of acidification (fCO2 ˜ 365-1231 µatm) and as a function of quantity and quality of their diet. We used an egg transplant experiment to reveal whether transgenerational effects can alleviate the possible negative effects of ocean acidification on offspring development. We found significant negative effects of ocean acidification on adult female size. In addition, we found signs of a possible threshold at high fCO2, above which adaptive maternal effects cannot alleviate the negative effects of acidification on egg-hatching and nauplii development. We did not find support for the hypothesis that insufficient food quantity (total particulate carbon < 55 µm) or quality (C : N) weakens the transgenerational effects. However, females with high-ORAC-produced eggs with high hatching success. Overall, these results indicate that Acartia sp. could be affected by projected near-future CO2 levels.

The Impact of Various Parental Mental Disorders on Children's Diagnoses: A Systematic Review.

Science.gov (United States)

van Santvoort, Floor; Hosman, Clemens M H; Janssens, Jan M A M; van Doesum, Karin T M; Reupert, Andrea; van Loon, Linda M A

2015-12-01

Children of mentally ill parents are at high risk of developing problems themselves. They are often identified and approached as a homogeneous group, despite diversity in parental diagnoses. Some studies demonstrate evidence for transgenerational equifinality (children of parents with various disorders are at risk of similar problems) and multifinality (children are at risk of a broad spectrum of problems). At the same time, other studies indicate transgenerational specificity (child problems are specifically related to the parent's diagnosis) and concordance (children are mainly at risk of the same disorder as their parent). Better insight into the similarities and differences between children of parents with various mental disorders is needed and may inform the development and evaluation of future preventive interventions for children and their families. Accordingly, we systematically compared 76 studies on diagnoses in children of parents with the most prevalent axis I disorders: unipolar depression, bipolar disorder, and anxiety disorders. Methodological characteristics of the studies were compared, and outcomes were analyzed for the presence of transgenerational equifinality, multifinality, specificity, and concordance. Also, the strengths of the relationships between child and parent diagnoses were investigated. This review showed that multifinality and equifinality appear to be more of a characteristic of children of unipolar and bipolar parents than of children of anxious parents, whose risk is mainly restricted to developing anxiety disorders. For all children, risk transmission is assumed to be partly specific since the studies indicate a strong tendency for children to develop the same disorder as their parent.

Epigenetic Mechanisms of Depression and Antidepressants Action

Science.gov (United States)

Vialou, Vincent; Feng, Jian; Robison, Alfred J.; Nestler, Eric J.

2013-01-01

Epigenetic mechanisms, which control chromatin structure and function, mediate changes in gene expression that occur in response to diverse stimuli. Recent research has established that environmental events and behavioral experience induce epigenetic changes at particular gene loci that help shape neuronal plasticity and function, and hence behavior, and that some of these changes can be very stable and even persist for a lifetime. Increasing evidence supports the hypothesis that aberrations in chromatin remodeling and subsequent effects on gene expression within limbic brain regions contribute to the pathogenesis of depression and other stress-related disorders such as post-traumatic stress disorder and other anxiety syndromes. Likewise, the gradually developing but persistent therapeutic effects of antidepressant medications may be achieved in part via epigenetic mechanisms. This review discusses recent advances in understanding epigenetic regulation of stress-related disorders and focuses on three distinct aspects of stress-induced epigenetic pathology: the effects of stress and antidepressant treatment during adulthood, the life-long effects of early life stress on subsequent stress vulnerability, and the possible trans-generational transmission of stress-induced abnormalities. PMID:23020296

An evolutionary perspective on the trans-generational basis of obesity.

Science.gov (United States)

Wells, Jonathan C K

2011-07-01

Until recently, obesity was considered the product of interactions between genotype and lifestyle. However, recent work suggests that the genetic heritability of adiposity has been over-estimated, whilst epidemiological studies show that although many genes are associated with nutritional status, the effect of each is very small. A polygenic basis of obesity risk may arise through bet-hedging of numerous traits to accommodate diverse unpredictable environments, rather than through systematic local adaptation. Such 'fragmentation' of the genetic component of metabolism across multiple alleles may be a necessary pre-requisite for complementary enhancement of phenotypic plasticity. The inter-generational component of obesity refers to phenotypic effects transmitted across generations, arising from exposure to maternal, familial and environmental niches during development. Inter-generational transfers of somatic capital (height, lean mass) may respond to ecological conditions through a slow-response damping system, through the influence of maternal phenotype on offspring growth and body composition. The primary traits subject to inter-generational effects may be physique and life history strategy, with adiposity both aiding and responding as a flexible risk management strategy. The biological processes that underpin the offspring's developmental plasticity appear sensitive to the obesogenic niche. Through this sensitivity, diverse environmental factors can induce excess weight gain from childhood onwards.

Development of radiation-induced mutation techniques and functional genomics studies

International Nuclear Information System (INIS)

Kim, Dong Sub; Kang, Si Yong; Kim, Jin Baek

2012-01-01

This project has been performed to develop plant genetic resources using radiation (gamma-rays, ion-beam, space environments), to conduct functional genomics studies with mutant resources, and to develop new radiation plant breeding techniques using various radiation sources during 3 years. In the first section, we developed flower genetic resources, functional crop resources, and bio-industrial plant resources. In the second section, we cloned several mutated genes and studied mechanisms of gene expression and genetic diversity of mutations induced by gamma-rays. In the third section, we developed new plant breeding techniques using gamma-phytotron, heavy ion-beam, and space environments. Based on these results, a total of 8 cultivars containing Chrysanthemum, Hibiscus, kenaf, rice, and soybean were applied for plant variety protection (PVP) and a total of 4 cultivars were registered for PVP. Also, license agreement for the dwarf type Hibiscus mutant 'Ggoma' was conducted with Supro co. and the manufacturing technology for natural antioxidant pear-grape vinegar was transferred into Enzenic co. Also, 8 gene sequences, such as F3'H and LDOX genes associated with flower color in Chrysanthemum and EPSPS gene from Korean lawn grass, were registered in the database of National Center for Biotechnology Information (NCBI). In the future study, we will develop new radiation mutation breeding techniques through the mutation spectrum induced by various radiation sources, the studies for mechanism of the cellular response to radiation, and the comparative·structural·functional genomics studies for useful traits

The Impact of Various Parental Mental Disorders on Children's Diagnoses: A Systematic Review

NARCIS (Netherlands)

Santvoort, F. van; Hosman, C.M.H.; Janssens, J.M.A.M.; Doesum, K.T.M. van; Reupert, A.E.; Loon, L.M.A. van

2015-01-01

Children of mentally ill parents are at high risk of developing problems themselves. They are often identified and approached as a homogeneous group, despite diversity in parental diagnoses. Some studies demonstrate evidence for transgenerational equifinality (children of parents with various

Drugs of abuse in pregnancy, poor neonatal development, and future neurodegeneration. Is oxidative stress the culprit?

Science.gov (United States)

Neri, Margherita; Bello, Stefania; Turillazzi, Emanuela; Riezzo, Irene

2015-01-01

The abuse of licit and illicit drugs is a worldwide issue that is a cause for concern in pregnant women. It may lead to complications in pregnancy that may affect the mother, fetus, and /or neonate. The effects of any substance on the developing embryo and fetus are dependent upon dosing, timing, duration of drug exposure, and the extent of drug distribution. Teratogenic effects have been described when exposure takes place during the embryonic stage; however drugs have subtle effects, including abnormal growth and/or maturation, alterations in neurotransmitters and their receptors, and brain organization. The mechanisms by which intrauterine exposure to many substances may result in neuronal injury have not been completely elucidated. Oxidative stress and epigenetic changes have been recently implicated in the pathogenesis of long - term adverse health sequelae, and neuro-developmental impairment in the offspring of addicted mothers. Transgenerational epigenetics may also explain the alarming datum that developmental abnormalities, impairment in learning and memory, and attention deficit can occur even in the absence of direct fetal exposure, when drugs are consumed prior to conception. There is a growing body of evidence demonstrating a link between redox state unbalance, epigenetic markers, developmental anomalies, and neurodegeneration. The reviewed literature data uphold redox homeostasis disruption as an important factor in the pathogenesis of drug of abuse- induced neurodegeneration, and highlight the potential for new therapies that could prevent neurodegeneration through antioxidant and epigenetic modulatory mechanisms. This therefore reveals important targets for novel neuroprotective strategies.

Epi-genetics modifications induced by a depleted uranium exposure in the zebra fish

Energy Technology Data Exchange (ETDEWEB)

Gombeau, K.; Pereira, S.; Adam-Guillermin, C. [IRSN/PRP-ENV/SERIS/LECO (France); Bourdineaud, J.P. [UMR CNRS 5805 EPOC (France); Ravanat, J.L. [INAC/Scib UMR E3 CEA-UJF (France)

2014-07-01

The work presented here integrates in the general framework of assessment of effects of chronic exposure to low doses of radionuclides. This evaluation necessarily involves the study of the mechanisms of toxic action at the cellular or subcellular level, in order to better understand the processes of propagation of effects to the level of the populations or ecosystems. As such, the question of the mechanisms underlying the trans-generational effects and the adaptive capacity of organisms is central, both in humans and in animal species. Epigenetic refer to changes in gene function that do not involve changes in DNA sequence, and which are transmitted in a hereditary manner by mitosis or meiosis. The latter plays a key role in these trans-generational effects. Among these changes, DNA-methylation is one of the most studied epigenetic parameters. This work is part of a PhD, included in the European COMET project (Euratom 7. Framework Program), and focuses on epigenetic modifications induced in zebra fish after a chronic exposure to radionuclides. Male and female fishes were exposed to 2 and 20 μg.L{sup -1} of depleted uranium for 24 days. After 7 and 24 days of exposure, brain, gonads, and eyes were collected in order to study changes in DNA methylation. In addition, genotoxicity was measured by the γH2AX assay. The overall changes in DNA methylation were studied by AFLP-MS and HPLC-MS, in order to know if the exposure to depleted uranium changes the global status of DNA methylation. We have found a decrease in the global level of methylation in the eyes of males after 24 days of exposure, the diminution being much more important and significant at the higher concentration of exposure (11.79 ± 3.62 against 52.43 ± 3.01 for controls) This study will be refined by analyzing the methylation of specific regions of the genome, because it represent the sequences of genes involved in major physiological functions and that may be subject to variations in the methylation

Lung Development and Aging.

Science.gov (United States)

Bush, Andrew

2016-12-01

The onset of chronic obstructive pulmonary disease (COPD) can arise either from failure to attain the normal spirometric plateau or from an accelerated decline in lung function. Despite reports from numerous big cohorts, no single adult life factor, including smoking, accounts for this accelerated decline. By contrast, five childhood risk factors (maternal and paternal asthma, maternal smoking, childhood asthma and respiratory infections) are strongly associated with an accelerated rate of lung function decline and COPD. Among adverse effects on lung development are transgenerational (grandmaternal smoking), antenatal (exposure to tobacco and pollution), and early childhood (exposure to tobacco and pollution including pesticides) factors. Antenatal adverse events can operate by causing structural changes in the developing lung, causing low birth weight and prematurity and altered immunological responses. Also important are mode of delivery, early microbiological exposures, and multiple early atopic sensitizations. Early bronchial hyperresponsiveness, before any evidence of airway inflammation, is associated with adverse respiratory outcomes. Overlapping cohort studies established that spirometry tracks from the preschool years to late middle age, and those with COPD in the sixth decade already had the worst spirometry at age 10 years. Alveolar development is now believed to continue throughout somatic growth and is adversely impacted by early tobacco smoke exposure. Genetic factors are also important, with genes important in lung development and early wheezing also being implicated in COPD. The inescapable conclusion is that the roots of COPD are in early life, and COPD is a disease of childhood adverse factors interacting with genetic factors.

Development of radiation-induced mutation techniques and functional genomics studies

Energy Technology Data Exchange (ETDEWEB)

Kim, Dong Sub; Kang, Si Yong; Kim, Jin Baek [KAERI, Daejeon (Korea, Republic of); and others

2012-01-15

This project has been performed to develop plant genetic resources using radiation (gamma-rays, ion-beam, space environments), to conduct functional genomics studies with mutant resources, and to develop new radiation plant breeding techniques using various radiation sources during 3 years. In the first section, we developed flower genetic resources, functional crop resources, and bio-industrial plant resources. In the second section, we cloned several mutated genes and studied mechanisms of gene expression and genetic diversity of mutations induced by gamma-rays. In the third section, we developed new plant breeding techniques using gamma-phytotron, heavy ion-beam, and space environments. Based on these results, a total of 8 cultivars containing Chrysanthemum, Hibiscus, kenaf, rice, and soybean were applied for plant variety protection (PVP) and a total of 4 cultivars were registered for PVP. Also, license agreement for the dwarf type Hibiscus mutant 'Ggoma' was conducted with Supro co. and the manufacturing technology for natural antioxidant pear-grape vinegar was transferred into Enzenic co. Also, 8 gene sequences, such as F3'H and LDOX genes associated with flower color in Chrysanthemum and EPSPS gene from Korean lawn grass, were registered in the database of National Center for Biotechnology Information (NCBI). In the future study, we will develop new radiation mutation breeding techniques through the mutation spectrum induced by various radiation sources, the studies for mechanism of the cellular response to radiation, and the comparative{center_dot}structural{center_dot}functional genomics studies for useful traits.

Friends with Social Benefits: Host-Microbe Interactions as a Driver of Brain Evolution and Development?

Directory of Open Access Journals (Sweden)

Roman M Stilling

2014-10-01

Full Text Available The tight association of the human body with trillions of colonizing microbes that we observe today is the result of a long evolutionary history. Only very recently have we started to understand how this symbiosis also affects brain function and behaviour. Here in this hypothesis and theory article, we propose how host-microbe associations potentially influenced mammalian brain evolution and development. In particular, we explore the integration of human brain development with evolution, symbiosis, and RNA biology, which together represent a ‘social triangle’ that drives human social behaviour and cognition. We argue that, in order to understand how inter-kingdom communication can affect brain adaptation and plasticity, it is inevitable to consider epigenetic mechanisms as important mediators of genome-microbiome interactions on an individual as well as a transgenerational time scale. Finally, we unite these interpretations with the hologenome theory of evolution. Taken together, we propose a tighter integration of neuroscience fields with host-associated microbiology by taking an evolutionary perspective.

Molecular characterization of a GA-inducible gene, Cvsus1, in developing watermelon seeds.

Science.gov (United States)

Kim, Joonyul; Jun, Sung-Hoon; Kang, Hong-Gyu; Lee, Jinwon; An, Gynheung

2002-10-31

To understand the molecular mechanisms that control seed development, we isolated a seed-preferential gene from ESTs of developing watermelon seeds. The gene Cvsus1 encodes a protein that is 86% identical to the Vicia faba sucrose synthase expressed in developing seeds. RNA blot analysis showed that Cvsus1 was preferentially expressed in watermelon seeds. We also investigated gene expression levels both in pollinated seeds and in parthenocarpic seeds, which lack zygotic tissues. Whereas the transcript level of Cvsus1 was rapidly increased during normal seed development, the expression was not significantly increased in the parthenocarpic seeds. However, treating the parthenocarpic fruits with GA3 strongly induced Cvsus1 expression, up to the level accumulated in pollinated seeds. These results suggest that Cvsus1 is induced in maternal tissues via signals from the zygotic tissues, and that GA may be one of those signals.

Development of resistance to serotonin-induced itch in bile duct ligated mice.

Science.gov (United States)

Ostadhadi, Sattar; Haddadi, Nazgol-Sadat; Foroutan, Arash; Azimi, Ehsan; Elmariah, Sarina; Dehpour, Ahmad-Reza

2017-06-01

Cholestatic itch can be severe and significantly impair the quality of life of patients. The serotonin system is implicated in cholestatic itch; however, the pruritogenic properties of serotonin have not been evaluated in cholestatic mice. Here, we investigated the serotonin-induced itch in cholestatic mice which was induced by bile duct ligation (BDL). Serotonin, sertraline or saline were administered intradermally to the rostral back area in BDL and sham operated (SHAM) mice, and the scratching behaviour was videotaped for 1 hour. Bile duct ligated mice had significantly increased scratching responses to saline injection on the seventh day after surgery. Additionally, serotonin or sertraline significantly induced scratching behaviour in BDL mice compared to saline at day 7 after surgery, while it did not induce itch at day 5. The scratching behaviour induced by serotonin or sertraline was significantly less in BDL mice compared to SHAM mice. Likewise, the locomotor activity of BDL or SHAM mice was not significantly different from unoperated (UNOP) mice on the fifth and seventh day, suggesting that the scratching behaviour was not affected by motor dysfunctions. Our data suggest that despite the potentiation of evoked itch, a resistance to serotonin-induced itch is developed in cholestatic mice. © 2017 John Wiley & Sons Australia, Ltd.

Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

Science.gov (United States)

Guzman, David Calderón; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; de la Cruz, Diego Zamora; Soto, Monica Punzo

2017-01-01

Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

Science.gov (United States)

Dong, Jing; Gao, Lingqi; Han, Junde; Zhang, Junjie; Zheng, Jijian

2017-07-01

Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.

Cytomegalovirus induces abnormal chondrogenesis and osteogenesis during embryonic mandibular development

Directory of Open Access Journals (Sweden)

Bringas Pablo

2008-03-01

Full Text Available Abstract Background Human clinical studies and mouse models clearly demonstrate that cytomegalovirus (CMV disrupts normal organ and tissue development. Although CMV is one of the most common causes of major birth defects in humans, little is presently known about the mechanism(s underlying CMV-induced congenital malformations. Our prior studies have demonstrated that CMV infection of first branchial arch derivatives (salivary glands and teeth induced severely abnormal phenotypes and that CMV has a particular tropism for neural crest-derived mesenchyme (NCM. Since early embryos are barely susceptible to CMV infection, and the extant evidence suggests that the differentiation program needs to be well underway for embryonic tissues to be susceptible to viral infection and viral-induced pathology, the aim of this study was to determine if first branchial arch NCM cells are susceptible to mCMV infection prior to differentiation of NCM derivatives. Results E11 mouse mandibular processes (MANs were infected with mouse CMV (mCMV for up to 16 days in vitro. mCMV infection of undifferentiated embryonic mouse MANs induced micrognathia consequent to decreased Meckel's cartilage chondrogenesis and mandibular osteogenesis. Specifically, mCMV infection resulted in aberrant stromal cellularity, a smaller, misshapen Meckel's cartilage, and mandibular bone and condylar dysmorphogenesis. Analysis of viral distribution indicates that mCMV primarily infects NCM cells and derivatives. Initial localization studies indicate that mCMV infection changed the cell-specific expression of FN, NF-κB2, RelA, RelB, and Shh and Smad7 proteins. Conclusion Our results indicate that mCMV dysregulation of key signaling pathways in primarily NCM cells and their derivatives severely disrupts mandibular morphogenesis and skeletogenesis. The pathogenesis appears to be centered around the canonical and noncanonical NF-κB pathways, and there is unusual juxtaposition of abnormal stromal

Ocean acidification challenges copepod phenotypic plasticity

Directory of Open Access Journals (Sweden)

A. Vehmaa

2016-11-01

Full Text Available Ocean acidification is challenging phenotypic plasticity of individuals and populations. Calanoid copepods (zooplankton are shown to be fairly plastic against altered pH conditions, and laboratory studies indicate that transgenerational effects are one mechanism behind this plasticity. We studied phenotypic plasticity of the copepod Acartia sp. in the course of a pelagic, large-volume mesocosm study that was conducted to investigate ecosystem and biogeochemical responses to ocean acidification. We measured copepod egg production rate, egg-hatching success, adult female size and adult female antioxidant capacity (ORAC as a function of acidification (fCO2  ∼  365–1231 µatm and as a function of quantity and quality of their diet. We used an egg transplant experiment to reveal whether transgenerational effects can alleviate the possible negative effects of ocean acidification on offspring development. We found significant negative effects of ocean acidification on adult female size. In addition, we found signs of a possible threshold at high fCO2, above which adaptive maternal effects cannot alleviate the negative effects of acidification on egg-hatching and nauplii development. We did not find support for the hypothesis that insufficient food quantity (total particulate carbon < 55 µm or quality (C : N weakens the transgenerational effects. However, females with high-ORAC-produced eggs with high hatching success. Overall, these results indicate that Acartia sp. could be affected by projected near-future CO2 levels.

Ocean acidification challenges copepod reproductive plasticity

Science.gov (United States)

Vehmaa, A.; Almén, A.-K.; Brutemark, A.; Paul, A.; Riebesell, U.; Furuhagen, S.; Engström-Öst, J.

2015-11-01

Ocean acidification is challenging phenotypic plasticity of individuals and populations. Calanoid copepods (zooplankton) are shown to be fairly plastic against altered pH conditions, and laboratory studies indicate that transgenerational effects are one mechanism behind this plasticity. We studied phenotypic plasticity of the copepod Acartia bifilosa in the course of a pelagic, large-volume mesocosm study that was conducted to investigate ecosystem and biogeochemical responses to ocean acidification. We measured copepod egg production rate, egg hatching success, adult female size and adult female antioxidant capacity (ORAC) as a function of acidification (fCO2 ~ 365-1231 μatm), and as a function of quantity and quality of their diet. We used an egg transplant experiment to reveal if transgenerational effects can alleviate the possible negative effects of ocean acidification on offspring development. We found significant negative effects of ocean acidification on adult female copepod size and egg hatching success. In addition, we found a threshold of fCO2 concentration (~ 1000 μatm), above which adaptive maternal effects cannot alleviate the negative effects of acidification on egg hatching and nauplii development. We did not find support for the hypothesis that insufficient food quantity (total particulate carbon ~ 55 μm) or quality (C : N) weakens the transgenerational effects. However, females with high ORAC produced eggs with high hatching success. Overall, these results indicate that A. bifilosa could be affected by projected near future CO2 levels.

Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice.

Science.gov (United States)

Xu, De-Xiang; Chen, Yuan-Hua; Zhao, Lei; Wang, Hua; Wei, Wei

2006-12-01

Maternal infection is a cause of adverse developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Lipopolysaccharide-induced developmental toxicity at early gestational stages has been well characterized. The purpose of the present study was to investigate the effects of maternal lipopolysaccharide exposure at late gestational stages on intrauterine fetal growth and skeletal development and to assess the potential role of reactive oxygen species in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation. The timed pregnant CD-1 mice were intraperitoneally injected with lipopolysaccharide (25 to 75 microg/kg per day) on gestational day 15 to 17. To investigate the role of reactive oxygen species on lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation, the pregnant mice were injected with alpha-phenyl-N-t-butylnitrone (100 mg/kg, intraperitoneally) at 30 minutes before lipopolysaccharide (75 microg/kg per day, intraperitoneally), followed by an additional dose of alpha-phenyl-N-t-butylnitrone (50 mg/kg, intraperitoneally) at 3 hours after lipopolysaccharide. The number of live fetuses, dead fetuses, and resorption sites was counted on gestational day 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Maternal lipopolysaccharide exposure significantly increased fetal mortality, reduced fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone in a dose-dependent manner. Alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, almost completely blocked lipopolysaccharide-induced fetal death (63.2% in lipopolysaccharide group versus 6.5% in alpha-phenyl-N-t-butylnitrone + lipopolysaccharide group, P intrauterine growth restriction

Protective effect of pyruvate against ethanol-induced apoptotic neurodegeneration in the developing rat brain.

Science.gov (United States)

Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Lee, Hae Young; Koh, Phil Ok; Kim, Myeong Ok

2011-12-01

Exposure to alcohol during the early stages of brain development can lead to neurological disorders in the CNS. Apoptotic neurodegeneration due to ethanol exposure is a main feature of alcoholism. Exposure of developing animals to alcohol (during the growth spurt period in particular) elicits apoptotic neuronal death and causes fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS). A single episode of ethanol intoxication (at 5 g/kg) in a seven-day-old developing rat can activate the apoptotic cascade, leading to widespread neuronal death in the brain. In the present study, we investigated the potential protective effect of pyruvate against ethanol-induced neuroapoptosis. After 4h, a single dose of ethanol induced upregulation of Bax, release of mitochondrial cytochrome-c into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1), all of which promote apoptosis. These effects were all reversed by co-treatment with pyruvate at a well-tolerated dosage (1000 mg/kg). Histopathology performed at 24 and 48 h with Fluoro-Jade-B and cresyl violet stains showed that pyruvate significantly reduced the number of dead cells in the cerebral cortex, hippocampus and thalamus. Immunohistochemical analysis at 24h confirmed that ethanol-induced cell death is both apoptotic and inhibited by pyruvate. These findings suggest that pyruvate treatment attenuates ethanol-induced neuronal cell loss in the developing rat brain and holds promise as a safe therapeutic and neuroprotective agent in the treatment of neurodegenerative disorders in newborns and infants. Copyright © 2011 Elsevier Ltd. All rights reserved.

Transgenerationale Wertevermittlung in der Familie

DEFF Research Database (Denmark)

Demuth, Carolin

2014-01-01

The present article investigates trans-generational aspects of identification with and dissociation from values within the family of origin in biographical-narrative constructions of young adults. The paper specifically focuses on the dimensions autonomy and relatedness which can be considered...... basic human needs that are negotiated differently in diverse socio-cultural contexts. As part of a larger longi- tudinal study biographical-narrative interviews were conducted with 24 young adults and a typology of life stories developed. Two distinct developmental pa- thways shall in the following...... be illustrated by individual case descriptions. We discuss how the orientations expressed in these life stories can be understood as part of trans-generational transmission on the one hand, and as inseparably inter- woven within the specific socio-historical and socio-cultural context in which they were produced...

Optimization of microwave-induced chemical etching for rapid development of neutron-induced recoil tracks in CR-39 detectors

International Nuclear Information System (INIS)

Sahoo, G.S.; Tripathy, S.P.; Bandyopadhyay, T.

2014-01-01

A systematic investigation is carried out to optimize the recently established microwave-induced chemical etching (MICE) parameters for rapid development of neutron-induced recoil tracks in CR-39 detectors. Several combinations of all available microwave powers with different etching durations were analysed to determine the most suitable etching condition. The etching duration was found to reduce with increasing microwave power and the tracks were observed at about 18, 15, 12, and 6 min for 300, 450, 600 and 900 W of microwave powers respectively compared to a few hours in chemical etching (CE) method. However, for complete development of tracks the etching duration of 30, 40, 50 and 60 min were found to be suitable for the microwave powers of 900, 600, 450 and 300 W, respectively. Temperature profiles of the etchant for all the available microwave powers at different etching durations were generated to regulate the etching process in a controlled manner. The bulk etch rates at different microwave powers were determined by 2 methods, viz., gravimetric and removed thickness methods. A logarithmic expression was used to fit the variation of bulk etch rate with microwave power. Neutron detection efficiencies were obtained for all the cases and the results on track parameters obtained with MICE technique were compared with those obtained from another detector processed with chemical etching. - Highlights: • Microwave-induced chemical etching method is optimized for rapid development of recoil tracks due to neutrons in CR-39 detector. • Several combinations of microwave powers and etching durations are investigated to standardize the suitable etching condition. • Bulk-etch rates are determined for all microwave powers by two different methods, viz. gravimetric and removed thickness method. • The method is found to be simple, effective and much faster compared to conventional chemical etching

Transgenerational effects of stress exposure on offspring phenotypes in apomictic dandelion

NARCIS (Netherlands)

Verhoeven, K.J.F.; Van Gurp, T.P.

2012-01-01

Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various

Transgenerational Effects of Stress Exposure on Offspring Phenotypes in Apomictic Dandelion

NARCIS (Netherlands)

Verhoeven, K.J.F.; Gurp, van T.P.

2012-01-01

Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various

Development of Laser-Induced Fluorescence Diagnostic for the Paul Trap Simulator Experiment

CERN Document Server

Chung, Moses; Efthimion, Philip; Gilson, Erik P; Majeski, Richard; Startsev, Edward

2005-01-01

The Paul Trap Simulator Experiment (PTSX) is a cylindrical Paul trap whose purpose is to simulate the nonlinear dynamics of intense charged particle beam propagation in alternating-gradient magnetic transport systems. For the in-situ measurement of the transverse ion density profile in the PTSX device, which is essential for the study of beam mismatch and halo particle production, a laser-induced fluorescence diagnostic system is being developed. Instead of cesium, which has been used in the initial phase of the PTSX experiment, barium has been selected as the preferred ion for the laser-induced fluorescence diagnostic. The installation of the barium ion source and the characterization of the tunable dye laser system are discussed. The design of the collection optics with an intensified CCD camera system is also discussed. Finally, initial test results using the laser-induced fluorescence diagnostic will be presented.

Rapid adaptive responses to climate change in corals

KAUST Repository

Torda, Gergely; Donelson, Jennifer M.; Aranda, Manuel; Barshis, Daniel J.; Bay, Line; Berumen, Michael L.; Bourne, David G.; Cantin, Neal; Foret, Sylvain; Matz, Mikhail; Miller, David J.; Moya, Aurelie; Putnam, Hollie M.; Ravasi, Timothy; van Oppen, Madeleine J. H.; Thurber, Rebecca Vega; Vidal-Dupiol, Jeremie; Voolstra, Christian R.; Watson, Sue-Ann; Whitelaw, Emma; Willis, Bette L.; Munday, Philip L.

2017-01-01

Pivotal to projecting the fate of coral reefs is the capacity of reef-building corals to acclimatize and adapt to climate change. Transgenerational plasticity may enable some marine organisms to acclimatize over several generations and it has been hypothesized that epigenetic processes and microbial associations might facilitate adaptive responses. However, current evidence is equivocal and understanding of the underlying processes is limited. Here, we discuss prospects for observing transgenerational plasticity in corals and the mechanisms that could enable adaptive plasticity in the coral holobiont, including the potential role of epigenetics and coral-associated microbes. Well-designed and strictly controlled experiments are needed to distinguish transgenerational plasticity from other forms of plasticity, and to elucidate the underlying mechanisms and their relative importance compared with genetic adaptation.

Rapid adaptive responses to climate change in corals

KAUST Repository

Torda, Gergely

2017-09-01

Pivotal to projecting the fate of coral reefs is the capacity of reef-building corals to acclimatize and adapt to climate change. Transgenerational plasticity may enable some marine organisms to acclimatize over several generations and it has been hypothesized that epigenetic processes and microbial associations might facilitate adaptive responses. However, current evidence is equivocal and understanding of the underlying processes is limited. Here, we discuss prospects for observing transgenerational plasticity in corals and the mechanisms that could enable adaptive plasticity in the coral holobiont, including the potential role of epigenetics and coral-associated microbes. Well-designed and strictly controlled experiments are needed to distinguish transgenerational plasticity from other forms of plasticity, and to elucidate the underlying mechanisms and their relative importance compared with genetic adaptation.

The Influence of Ghrelin on the Development of Dextran Sodium Sulfate-Induced Colitis in Rats

Directory of Open Access Journals (Sweden)

Aleksandra Matuszyk

2015-01-01

Full Text Available Ghrelin has protective and therapeutic effects in the gut. The aim of present studies was to investigate the effect of treatment with ghrelin on the development of colitis evoked by dextran sodium sulfate (DSS. Methods. Studies have been performed on rats. Colitis was induced by adding 5% DSS to the drinking water for 5 days. During this period animals were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 8 nmol/kg/dose. On the sixth day, animals were anesthetized and the severity of colitis was assessed. Results. Treatment with ghrelin during administration of DSS reduced the development of colitis. Morphological features of colonic mucosa exhibited a reduction in the area and deep of mucosal damage. Ghrelin reversed the colitis-induced decrease in blood flow, DNA synthesis, and superoxide dismutase activity in colonic mucosa. These effects were accompanied by a decrease in the colitis-evoked increase in mucosal concentration of interleukin-1β and malondialdehyde. Treatment with ghrelin reversed the DSS-induced reduction in body weight gain. Conclusions. Administration of ghrelin exhibits the preventive effect against the development of DSS-induced colitis. This effect seems to be related to ghrelin’s anti-inflammatory and antioxidative properties.

Development and assessment of countermeasure formulations for treatment of lung injury induced by chlorine inhalation

Energy Technology Data Exchange (ETDEWEB)

Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Chen, Jing; Schlueter, Connie F.; Mo, Yiqun; Humphrey, David M. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Rawson, Greg; Niño, Joe A.; Carson, Kenneth H. [Microencapsulation and Nanomaterials Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX (United States)

2016-05-01

Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposed mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Countermeasures for treatment of chlorine-induced acute lung injury are needed. • Formulations containing rolipram, triptolide, or budesonide were produced. • Formulations with a wide range of release properties were developed. • Countermeasure formulations inhibited chlorine-induced lung injury in mice.

TIM-3 is not essential for development of airway inflammation induced by house dust mite antigens

Directory of Open Access Journals (Sweden)

Yoshihisa Hiraishi

2016-10-01

Conclusions: Our findings indicate that, in mice, TIM-3 is not essential for development of HDM-induced acute or chronic allergic airway inflammation, although it appears to be involved in reduced lymphocyte recruitment during HDM-induced chronic allergic airway inflammation.

Induction, development, and inhibition of radiation-induced macrobodies

International Nuclear Information System (INIS)

Adam, W.J.; Grunewald, R.

1975-01-01

Coleus shoots were exposed to 100,000 R of γ radiation and the fine structure of the apical meristems was examined. Meristems were fixed at various postirradiation times. An ultrastructural body was found associated with irradiated tissue, bound by a single membrane, containing dense osmiophilic bodies, and usually associated with radiation-induced vacuoles. The development of these new bodies, and the effects of both dose rate and light during the postirradiation period on their development were examined. Reduction of the dose rate by a factor of two inhibited the formation of these macrobodies through the 24 hour postirradiation period. Meristems kept in the dark during the 24 hour postirradiation period had macrobodies similar in form to the macrobodies from the meristems of the 16 hour postirradiation period which were exposed to light. Superlethal doses were used to achieve these results. Similarities between our results and those achieved with lower lethal doses are discussed

Nicotinamide Inhibits Ethanol-Induced Caspase-3 and PARP-1 Over-activation and Subsequent Neurodegeneration in the Developing Mouse Cerebellum.

Science.gov (United States)

Ieraci, Alessandro; Herrera, Daniel G

2018-06-01

Fetal alcohol spectrum disorder (FASD) is the principal preventable cause of mental retardation in the western countries resulting from alcohol exposure during pregnancy. Ethanol-induced massive neuronal cell death occurs mainly in immature neurons during the brain growth spurt period. The cerebellum is one of the brain areas that are most sensitive to ethanol neurotoxicity. Currently, there is no effective treatment that targets the causes of these disorders and efficient treatments to counteract or reverse FASD are desirable. In this study, we investigated the effects of nicotinamide on ethanol-induced neuronal cell death in the developing cerebellum. Subcutaneous administration of ethanol in postnatal 4-day-old mice induced an over-activation of caspase-3 and PARP-1 followed by a massive neurodegeneration in the developing cerebellum. Interestingly, treatment with nicotinamide, immediately or 2 h after ethanol exposure, diminished caspase-3 and PARP-1 over-activation and reduced ethanol-induced neurodegeneration. Conversely, treatment with 3-aminobenzadine, a specific PARP-1 inhibitor, was able to completely block PARP-1 activation, but not caspase-3 activation or ethanol-induced neurodegeneration in the developing cerebellum. Our results showed that nicotinamide reduces ethanol-induced neuronal cell death and inhibits both caspase-3 and PARP-1 alcohol-induced activation in the developing cerebellum, suggesting that nicotinamide might be a promising and safe neuroprotective agent for treating FASD and other neurodegenerative disorders in the developing brain that shares similar cell death pathways.

Heritable Variation in Quinone-Induced Haustorium Development in the Parasitic Plant Triphysaria1

Science.gov (United States)

Jamison, Denneal S.; Yoder, John I.

2001-01-01

We are using the facultative hemiparasite, Triphysaria, as a model for studying host-parasite signaling in the Scrophulariaceae. Parasitic members of this family form subterranean connections, or haustoria, on neighboring host roots to access host water and nutrients. These parasitic organs develop in response to haustorial-inducing factors contained in host root exudates. A well-characterized inducing factor, 2, 6-dimethoxy-p-benzoquinone (DMBQ), can be used to trigger in vitro haustorium formation in the roots of Triphysaria. We have assayed three species, Triphysaria eriantha (Benth.) Chuang and Heckard, Triphysaria pusilla (Benth.) Chuang and Heckard, and Triphysaria versicolor Fischer and C. Meyer, for haustorium development in response to DMBQ. There were significant differences between the species in their ability to recognize and respond to this quinone. Ninety percent of T. versicolor individuals responded, whereas only 40% of T. pusilla and less than 10% of T. eriantha formed haustoria. Within field collections of self-pollinating T. pusilla, differential responsiveness to DMBQ was seen in distinct maternal families. Assaying haustorium development in subsequent generations of self-pollinated T. pusilla showed that DMBQ responsiveness was heritable. Reciprocal crosses between T. eriantha and T. versicolor demonstrated that DMBQ responsiveness was influenced by maternal factors. These results demonstrate heritable, natural variation in the recognition of a haustorial-inducing factor by a parasitic member of the Scrophulariaceae. PMID:11299366

Genetic requirements for Piwi-induced stable transgenerational gene silencing in Caenorhabditis elegans

OpenAIRE

Almeida, Miguel Duarte Dias de Vasconcelos, 1989-

2012-01-01

Tese de mestrado. Biologia (Biologia Evolutiva e do Desenvolvimento). Universidade de Lisboa, Faculdade de Ciências, 2012 A descoberta, em 1998, da interferência por RNA (RNAi) revelou que pequenos RNAs não codificantes estão envolvidos no controlo da expressão genética. Atualmente, várias vias de RNAi são conhecidas em Eucariotas. Apesar de divergirem em muitos aspetos, todas possuem complexos regulatórios envolvendo uma proteína Argonauta e um pequeno RNA. O complexo Argonauta-pequeno RN...

Bisphenol A in Reproduction: Epigenetic Effects.

Science.gov (United States)

Chianese, Rosanna; Troisi, Jacopo; Richards, Sean; Scafuro, Marika; Fasano, Silvia; Guida, Maurizio; Pierantoni, Riccardo; Meccariello, Rosaria

2018-02-21

Bisphenol A (BPA) is an endocrine disrupting chemical widely used in the manufacture of polycarbonate plastic and epoxy resin to produce a multitude of consumer products, food and drink containers, and medical devices. BPA is similar to estradiol in structure and thus interferes in steroid signalling with different outcomes on reproductive health depending on doses, life stage, mode, and timing of exposure. In this respect, it has an emerging and controversial role as a "reproductive toxicant" capable of inducing short and long-term effects including the modulation of gene expression through epigenetic modification (i.e. methylation of CpG islands, histone modifications and production of non-coding RNA) with direct and trans-generational effects on exposed organisms and their offspring, respectively. This review provides an overview about BPA effects on reproductive health and aims to summarize the epigenetic effects of BPA in male and female reproduction. BPA exerts epigenetic effects in both male and female reproduction. In males, BPA affects spermatogenesis and sperm quality and possible trans-generational effects on the reproductive ability of the offspring. In females, BPA affects ovary, embryo development, and gamete quality for successful in vivo and in vitro fertilization (IVF). The exact mechanisms of BPA-mediated effects in reproduction are not fully understood; however, the environmental exposure to BPA - especially in fetal and neonatal period - deserves attention to preserve the reproductive ability in both sexes and to reduce the epigenetic risk for the offspring. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Environmentally induced development costs underlie fitness tradeoffs.

Science.gov (United States)

Walter, Greg M; Wilkinson, Melanie J; Aguirre, J David; Blows, Mark W; Ortiz-Barrientos, Daniel

2018-06-01

environmentally dependent changes in development rate suggest that foreign environments induce organisms to develop at a rate different from their native habitat, incurring consequences for lifetime fitness and population divergence. © 2018 by the Ecological Society of America.

Fate of fluoride-induced subameloblastic cysts in developing hamster molar tooth germs

NARCIS (Netherlands)

Lyaruu, D.M.; Alberga, J.M.R.; Kwee, N.C.H.; Bervoets, T.J.M.; Bronckers, A.L.J.J.; Denbesten, P.K.

2011-01-01

White opacities and pits are developmental defects in enamel caused by high intake of fluoride (F) during amelogenesis. We tested the hypothesis that these enamel pits develop at locations where F induces the formation of sub-ameloblastic cysts. We followed the fate of these cysts during molar

Epigenetic control of mobile DNA as an interface between experience and genome change

Directory of Open Access Journals (Sweden)

James A. Shapiro

2014-04-01

Full Text Available Mobile DNA in the genome is subject to RNA-targeted epigenetic control. This control regulates the activity of transposons, retrotransposons and genomic proviruses. Many different life history experiences alter the activities of mobile DNA and the expression of genetic loci regulated by nearby insertions. The same experiences induce alterations in epigenetic formatting and lead to trans-generational modifications of genome expression and stability. These observations lead to the hypothesis that epigenetic formatting directed by non-coding RNA provides a molecular interface between life history events and genome alteration.

Abnormal development of tapetum and microspores induced by chemical hybridization agent SQ-1 in wheat.

Science.gov (United States)

Wang, Shuping; Zhang, Gaisheng; Song, Qilu; Zhang, Yingxin; Li, Zheng; Guo, Jialin; Niu, Na; Ma, Shoucai; Wang, Junwei

2015-01-01

Chemical hybridization agent (CHA)-induced male sterility is an important tool in crop heterosis. To demonstrate that CHA-SQ-1-induced male sterility is associated with abnormal tapetal and microspore development, the cytology of CHA-SQ-1-treated plant anthers at various developmental stages was studied by light microscopy, scanning and transmission electron microscopy, in situ terminal deoxynucleotidyl transferasemediated dUTP nick end-labelling (TUNEL) assay and DAPI staining. The results indicated that the SQ-1-treated plants underwent premature tapetal programmed cell death (PCD), which was initiated at the early-uninucleate stage of microspore development and continued until the tapetal cells were completely degraded; the process of microspore development was then blocked. Microspores with low-viability (fluorescein diacetate staining) were aborted. The study suggests that premature tapetal PCD is the main cause of pollen abortion. Furthermore, it determines the starting period and a key factor in CHA-SQ-1-induced male sterility at the cell level, and provides cytological evidence to further study the mechanism between PCD and male sterility.

Abnormal development of tapetum and microspores induced by chemical hybridization agent SQ-1 in wheat.

Directory of Open Access Journals (Sweden)

Shuping Wang

Full Text Available Chemical hybridization agent (CHA-induced male sterility is an important tool in crop heterosis. To demonstrate that CHA-SQ-1-induced male sterility is associated with abnormal tapetal and microspore development, the cytology of CHA-SQ-1-treated plant anthers at various developmental stages was studied by light microscopy, scanning and transmission electron microscopy, in situ terminal deoxynucleotidyl transferasemediated dUTP nick end-labelling (TUNEL assay and DAPI staining. The results indicated that the SQ-1-treated plants underwent premature tapetal programmed cell death (PCD, which was initiated at the early-uninucleate stage of microspore development and continued until the tapetal cells were completely degraded; the process of microspore development was then blocked. Microspores with low-viability (fluorescein diacetate staining were aborted. The study suggests that premature tapetal PCD is the main cause of pollen abortion. Furthermore, it determines the starting period and a key factor in CHA-SQ-1-induced male sterility at the cell level, and provides cytological evidence to further study the mechanism between PCD and male sterility.

Is Increased Low-dose somatic Radiosensitivity Associated with Increased Transgenerational Germline Mutation

International Nuclear Information System (INIS)

Brenner, David J.

2008-01-01

Using single-molecule polymerase chain reaction, the frequency of spontaneous and radiation-induced mutation at an expanded simple tandem repeat (ESTR) locus was studied in DNA samples extracted from sperm and bone marrow of Atm knockout (Atm+/-) heterozygous male mice. The frequency of spontaneous mutation in sperm and bone marrow in Atm+/- males did not significantly differ from that in wild-type BALB/c mice. Acute gamma-ray exposure did not affect ESTR mutation frequency in bone marrow and resulted in similar increases in sperm samples taken from Atm+/- and BALB/c males. Taken together, these results suggest that the Atm haploinsufficiency analyzed in our study does not affect spontaneous and radiation-induced ESTR mutation frequency in mice

Development of a monoclonal-based enzyme-linked immunoassay for saxitoxin-induced protein.

Science.gov (United States)

Smith, D S; Kitts, D D

1994-03-01

A monoclonal antibody was generated against saxitoxin-induced protein (SIP) from the small shore crab Hemigrapsus oregenesis. SIP was induced by saxitoxin injection and could be detected in the crude crab extracts with both polyclonal and monoclonal antibody preparations. On Western blots, the polyclonal serum reacted against several bands which were induced by saxitoxin in the crude extracts. These bands represented proteins related to SIP. The monoclonal (4G5), however, was specific for the 79,000 mol. wt subunit of SIP. A triple antibody sandwich ELISA was developed in which polyclonal anti-SIP IgG was used as a trapping layer and monoclonal 4G5 was used as the detection layer. This assay was shown to be more specific and more accurate than a direct bind assay which employed the polyclonal antiserum alone. Although the polyclonal serum was more sensitive than the monoclonal on Western blots, the triple antibody sandwich and direct bind ELISAs were of comparable sensitivity.

Methylcholanthrene-Induced Sarcomas Develop Independently from NOX2-Derived ROS.

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Maarten A Ligtenberg

Full Text Available Reactive oxygen species (ROS produced by the inducible NADPH oxidase type 2 (NOX2 complex are essential for clearing certain infectious organisms but may also have a role in regulating inflammation and immune response. For example, ROS is involved in myeloid derived suppressor cell (MDSC- and regulatory T cell (T(reg mediated T- and NK-cell suppression. However, abundant ROS produced within the tumor microenvironment, or by the tumor itself may also yield oxidative stress, which can blunt anti-tumor immune responses as well as eventually leading to tumor toxicity. In this study we aimed to decipher the role of NOX2-derived ROS in a chemically (by methylcholanthrene (MCA induced sarcoma model. Superoxide production by NOX2 requires the p47(phox (NCF1 subunit to organize the formation of the NOX2 complex on the cell membrane. Homozygous mutant mice (NCF1*/* have a functional loss of their super oxide burst while heterozygous mice (NCF1*/+ retain this key function. Mice harboring either a homo- or a heterozygous mutation were injected intramuscularly with MCA to induce sarcoma formation. We found that NOX2 functionality does not determine tumor incidence in the tested MCA model. Comprehensive immune monitoring in tumor bearing mice showed that infiltrating immune cells experienced an increase in their oxidative state regardless of the NOX2 functionality. While MCA-induced sarcomas where characterized by a T(reg and MDSC accumulation, no significant differences could be found between NCF1*/* and NCF1*/+ mice. Furthermore, infiltrating T cells showed an increase in effector-memory cell phenotype markers in both NCF1*/* and NCF1*/+ mice. Tumors established from both NCF1*/* and NCF1*/+ mice were tested for their in vitro proliferative capacity as well as their resistance to cisplatin and radiation therapy, with no differences being recorded. Overall our findings indicate that NOX2 activity does not play a key role in tumor development or immune cell

Hypoxia-inducible factor 1α regulates branching morphogenesis during kidney development.

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Tsuji, Kenji; Kitamura, Shinji; Makino, Hirofumi

2014-04-25

The kidneys are exposed to hypoxic conditions during development. Hypoxia-inducible factor (HIF), an important mediator of the response to hypoxia, is believed to have an important role in development. However, the relationship between HIF and branching morphogenesis has not been elucidated clearly. In this study, we examined whether HIF regulates kidney development. We harvested kidneys from day 13 rat embryos (E13Ks) and cultured the organs under normoxic (20% O2/5% CO2) or hypoxic (5% O2/5% CO2) conditions. We evaluated the kidneys based on morphology and gene expression. E13Ks cultured under hypoxic conditions had significantly more ureteric bud (UB) branching than the E13Ks cultured under normoxic conditions. In addition, the mRNA levels of GDNF and GDNF receptor (GFR-α1), increased under hypoxic conditions in E13Ks. When we cultured E13Ks with the HIF-1α inhibitor digoxin or with siRNA targeting HIF-1α under hypoxic conditions, we did not observe increased UB branching. In addition, the expression of GDNF and GFR-α1 was inhibited under hypoxic conditions when the kidneys were treated with siRNA targeting HIF-1α. We also elucidated that hypoxia inhibited UB cell apoptosis and promoted the expression of FGF7 mRNA levels in metanephric mesenchymal (MM) cells in vitro. These findings suggest that hypoxic condition has important roles in inducing branching morphogenesis during kidney development. Hypoxia might mediate branching morphogenesis via not only GDNF/Ret but also FGF signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

Pre- and post-natal nutritional factors in the metabolic regulation of obesity

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E. Villanueva-Ortega

2017-04-01

Full Text Available In recent decades there has been a very significant increase in obesity in most developing countries. In addition to environmental, genetic and hormonal factors, nutritional and maternal environment factors influencing critical periods of foetal development have acquired increasing significance since the thrifty phenotype theory was described by Harles and Barker and epidemiological studies demonstrated that perinatal conditions may modify individuals’ future metabolic responses via genomic reprogramming. Perinatal programming corresponds to a critical and accelerated period of developmental plasticity from preconception through early postnatal life. This characteristic may also have a long-term influence on metabolic health and obesity. Epigenetic modifications favour the survival of the individual in critical periods when nutritional restriction is established, but exerts long-term risks, as metabolic programming tracks into infancy and adulthood and induces fat mass accumulation, particularly if energy consumption is exceeded. Although the mechanisms are not yet fully understood, it is evident that hormonal factors such as insulin and leptin may influence the programming of hypothalamic circuits for energy balance regulation. Nutritional interventions in animal models at critical stages of development have demonstrated that microenvironmental modifications might induce a permanent modulation of the progeny genome expression via epigenetic mechanisms. A transgenerational transmission of obesity has been proposed.

CISH is induced during DC development and regulates DC-mediated CTL activation.

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Miah, Mohammad Alam; Yoon, Cheol-Hee; Kim, Joonoh; Jang, Jinah; Seong, Young-Rim; Bae, Yong-Soo

2012-01-01

The cytokine inducible SH2-domain protein (CISH) is a well-known STAT5 target gene, but its role in the immune system remains uncertain. In this study, we found that CISH is predominantly induced during dendritic cell (DC) development from mouse bone marrow (BM) cells and plays a crucial role in type 1 DC development and DC-mediated CTL activation. CISH knockdown reduced the expression of MHC class I, co-stimulatory molecules and pro-inflammatory cytokines in BMDCs. Meanwhile, the DC yield was markedly enhanced by CISH knockdown via cell-cycle activation and reduction of cell apoptosis. Down-regulation of cell proliferation at the later stage of DC development was found to be associated with CISH-mediated negative feedback regulation of STAT5 activation. In T-cell immunity, OT-1 T-cell proliferation was significantly reduced by CISH knockdown in DCs, whereas OT-2 T-cell proliferation was not affected by CISH knockdown. CTLs generated by DC vaccination were also markedly reduced by CISH knockdown, followed by significant impairment of DC-based tumor immunotherapy. Taken together, our data suggest that CISH expression at the later stage of DC development triggers the shutdown of DC progenitor cell proliferation and facilitates DC differentiation into a potent stimulator of CTLs. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line

Energy Technology Data Exchange (ETDEWEB)

Vendramini-Costa, Débora Barbosa, E-mail: vendramini.debora@gmail.com [Department of Organic Chemistry, Institute of Chemistry, University of Campinas, Campinas, SP (Brazil); Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas, Campinas, SP (Brazil); Alcaide, Antonio [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain); Pelizzaro-Rocha, Karin Juliane [Department of Biochemistry, Institute of Biology, University of Campinas, Campinas, SP (Brazil); Talero, Elena; Ávila-Román, Javier [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain); Garcia-Mauriño, Sofia [Department of Plant Biology and Ecology, Faculty of Biology, University of Seville, Seville (Spain); Pilli, Ronaldo Aloise [Department of Organic Chemistry, Institute of Chemistry, University of Campinas, Campinas, SP (Brazil); Carvalho, João Ernesto de [Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas, Campinas, SP (Brazil); Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, SP (Brazil); Motilva, Virginia [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain)

2016-06-01

Colon cancer is the third most incident type of cancer worldwide. One of the most important risk factors for colon cancer development are inflammatory bowel diseases (IBD), thus therapies focusing on IBD treatment have great potential to be used in cancer prevention. Nature has been a source of new therapeutic and preventive agents and the racemic form of the styryl-lactone goniothalamin (GTN) has been shown to be a promising antiproliferative agent, with gastroprotective, antinociceptive and anti-inflammatory effects. As inflammation is a well-known tumor promoter, the major goal of this study was to evaluate the therapeutic and preventive potentials of GTN on chemically induced and spontaneous colitis, as well as the cytotoxic effects of GTN on a human colon tumor cell line (HT-29). GTN treatments inhibited TNBS-induced acute and chronic colitis development in Wistar rats, reducing myeloperoxidase levels and inflammatory cells infiltration in the mucosa. In spontaneous-colitis using IL-10 deficient mice (C57BL/6 background), GTN prevented colitis development through downregulation of TNF-α, upregulation of SIRT-1 and inhibition of proliferation (PCNA index), without signs of toxicity after three months of treatment. In HT-29 cells, treatment with 10 μM of GTN induced apoptosis by increasing BAX/BCL2, p-JNK1/JNK1, p-P38/P38 ratios as well as through ROS generation. Caspase 8, 9 and 3 activation also occurred, suggesting caspase-dependent apoptotic pathway, culminating in PARP-1 cleavage. Together with previous data, these results show the importance of GTN as a pro-apoptotic, preventive and therapeutic agent for IBD and highlight its potential as a chemopreventive agent for colon cancer. - Highlights: • Goniothalamin (GTN) inhibits the development of TNBS-induced colitis in rats. • Moreover, GTN prevents the development of spontaneous colitis in IL-10 deficient mice. • This activity relies on downregulation of TNF-α and upregulation of SIRT-1 expression

Development of turbopump cavitation performance test facility and the test of inducer performance

International Nuclear Information System (INIS)

Sohn, Dong Kee; Kim, Chun Tak; Yoon, Min Soo; Cha, Bong Jun; Kim, Jin Han; Yang, Soo Seok

2001-01-01

A performance test facility for turbopump inducer cavitation was developed and the inducer cavitation performance tests were performed. Major components of the performance test facility are driving unit, test section, piping, water tank, and data acquisition and control system. The maximum of testing capability of this facility are as follows: flow rate - 30kg/s; pressure - 13 bar, rotational speed - 10,000rpm. This cavitation test facility is characterized by the booster pump installed at the outlet of the pump that extends the flow rate range, and by the pressure control system that makes the line pressure down to vapor pressure. The vacuum pump is used for removing the dissolved air in the water as well as the line pressure. Performance tests were carried out and preliminary data of test model inducer were obtained. The cavitation performance test and cavitation bubble flow visualization were also made. This facility is originally designed for turbopump inducer performance test and cavitation test. However it can be applied to the pump impeller performance test in the future with little modification

Rhein Induces Oxidative Stress and Apoptosis in Mouse Blastocysts and Has Immunotoxic Effects during Embryonic Development

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Chien-Hsun Huang

2017-09-01

Full Text Available Rhein, a glucoside chemical compound found in a traditional Chinese medicine derived from the roots of rhubarb, induces cell apoptosis and is considered to have high potential as an antitumor drug. Several previous studies showed that rhein can inhibit cell proliferation and trigger mitochondria-related or endoplasmic reticulum (ER stress-dependent apoptotic processes. However, the side effects of rhein on pre- and post-implantation embryonic development remain unclear. Here, we show that rhein has cytotoxic effects on blastocyst-stage mouse embryos and induces oxidative stress and immunotoxicity in mouse fetuses. Blastocysts incubated with 5–20 μM rhein showed significant cell apoptosis, as well as decreases in their inner cell mass cell numbers and total cell numbers. An in vitro development assay showed that rhein affected the developmental potentials of both pre- and post-implantation embryos. Incubation of blastocysts with 5–20 μM rhein was associated with increased resorption of post-implantation embryos and decreased fetal weight in an embryo transfer assay. Importantly, in an in vivo model, intravenous injection of dams with rhein (1, 3, and 5 mg/kg body weight/day for four days resulted in apoptosis of blastocyst-stage embryos, early embryonic developmental injury, and decreased fetal weight. Intravenous injection of dams with 5 mg/kg body weight/day rhein significantly increased the total reactive oxygen species (ROS content of fetuses and the transcription levels of antioxidant proteins in fetal livers. Additional work showed that rhein induced apoptosis through ROS generation, and that prevention of apoptotic processes effectively rescued the rhein-induced injury effects on embryonic development. Finally, the transcription levels of the innate-immunity related genes, CXCL1, IL-1 β and IL-8, were down-regulated in the fetuses of dams that received intravenous injections of rhein. These results collectively show that rhein has

Effects of magnolol on UVB-induced skin cancer development in mice and its possible mechanism of action

International Nuclear Information System (INIS)

Chilampalli, Chandeshwari; Guillermo, Ruth; Zhang, Xiaoying; Kaushik, Radhey S; Young, Alan; Zeman, David; Hildreth, Michael B; Fahmy, Hesham; Dwivedi, Chandradhar

2011-01-01

Magnolol, a plant lignan isolated from the bark and seed cones of Magnolia officinalis, has been shown to have chemopreventive effects on chemically-induced skin cancer development. The objectives of this investigation are to study the anticarcinogenic effects of magnolol on UVB-induced skin tumor development in SKH-1 mice, a model relevant to humans, and determine the possible role of apoptosis and cell cycle arrest involved in the skin tumor development. UVB-induced skin carcinogenesis model in SKH-1 mice was used for determining the preventive effects of magnolol on skin cancer development. Western blottings and flow cytometric analysis were used to study the effects of magnolol on apoptosis and cell cycle. Magnolol pretreated groups (30, 60 μ g) before UVB treatments (30 mJ/cm 2 , 5 days/week) resulted in 27-55% reduction in tumor multiplicity as compared to control group in SKH-1 mice. Magnolol pretreatment increased the cleavage of caspase-8 and poly-(-ADP-ribose) polymerase (PARP), increased the expression of p21, a cell cycle inhibitor, and decreased the expression of proteins involved in the G2/M phase of cell cycle in skin samples from SKH-1 mice. Treatment of A431 cells with magnolol decreased cell viability and cell proliferation in a concentration dependent manner. Magnolol induced G2/M phase cell cycle arrest in A431 cells at 12 h with a decreased expression of cell cycle proteins such as cyclin B1, cyclin A, CDK4, Cdc2 and simultaneous increase in the expression of Cip/p21, a cyclin-dependent kinase inhibitor. Magnolol induced apoptosis in vivo and in vitro with an increased cleavage of caspase-8 and PARP. Phospho-signal transducers and activators of transcription 3 (Tyr 705 ), B-Raf, p-MEK, and p-AKT were down-regulated, whereas phosphorylation of ERK was induced by magnolol in A431 cells. Magnolol pretreatments prevent UVB-induced skin cancer development by enhancing apoptosis, causing cell cycle arrest at G2/M phase, and affecting various

Transgenerational Exposure to Environmental Tobacco Smoke

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Xavier Joya

2014-07-01

Full Text Available Traditionally, nicotine from second hand smoke (SHS, active or passive, has been considered the most prevalent substance of abuse used during pregnancy in industrialized countries. Exposure to environmental tobacco smoke (ETS is associated with a variety of health effects, including lung cancer and cardiovascular diseases. Tobacco is also a major burden to people who do not smoke. As developing individuals, newborns and children are particularly vulnerable to the negative effects of SHS. In particular, prenatal ETS has adverse consequences during the entire childhood causing an increased risk of abortion, low birth weight, prematurity and/or nicotine withdrawal syndrome. Over the last years, a decreasing trend in smoking habits during pregnancy has occurred, along with the implementation of laws requiring smoke free public and working places. The decrease in the incidence of prenatal tobacco exposure has usually been assessed using maternal questionnaires. In order to diminish bias in self-reporting, objective biomarkers have been developed to evaluate this exposure. The measurement of nicotine and its main metabolite, cotinine, in non-conventional matrices such as cord blood, breast milk, hair or meconium can be used as a non-invasive measurement of prenatal SMS in newborns. The aim of this review is to highlight the prevalence of ETS (prenatal and postnatal using biomarkers in non-conventional matrices before and after the implementation of smoke free policies and health effects related to this exposure during foetal and/or postnatal life.

Phytoplasma effector SAP54 induces indeterminate leaf-like flower development in Arabidopsis plants.

Science.gov (United States)

MacLean, Allyson M; Sugio, Akiko; Makarova, Olga V; Findlay, Kim C; Grieve, Victoria M; Tóth, Réka; Nicolaisen, Mogens; Hogenhout, Saskia A

2011-10-01

Phytoplasmas are insect-transmitted bacterial plant pathogens that cause considerable damage to a diverse range of agricultural crops globally. Symptoms induced in infected plants suggest that these phytopathogens may modulate developmental processes within the plant host. We report herein that Aster Yellows phytoplasma strain Witches' Broom (AY-WB) readily infects the model plant Arabidopsis (Arabidopsis thaliana) ecotype Columbia, inducing symptoms that are characteristic of phytoplasma infection, such as the production of green leaf-like flowers (virescence and phyllody) and increased formation of stems and branches (witches' broom). We found that the majority of genes encoding secreted AY-WB proteins (SAPs), which are candidate effector proteins, are expressed in Arabidopsis and the AY-WB insect vector Macrosteles quadrilineatus (Hemiptera; Cicadellidae). To identify which of these effector proteins induce symptoms of phyllody and virescence, we individually expressed the effector genes in Arabidopsis. From this screen, we have identified a novel AY-WB effector protein, SAP54, that alters floral development, resulting in the production of leaf-like flowers that are similar to those produced by plants infected with this phytoplasma. This study offers novel insight into the effector profile of an insect-transmitted plant pathogen and reports to our knowledge the first example of a microbial pathogen effector protein that targets flower development in a host.

Laser-induced microstructural development and phase evolution in magnesium alloy

International Nuclear Information System (INIS)

Guan, Y.C.; Zhou, W.; Li, Z.L.; Zheng, H.Y.

2014-01-01

Highlights: • Secondary phase evolution caused by laser processing was firstly reported. • Microstructure development was controlled by heat flow thermodynamics and kinetics. • Solid-state transformation resulted in submicron and nano-scale precipitates. • Cluster-shaped particles in overlapped region were due to precipitation coarsening. • Properties of materials can be tailored selectively by laser processing. -- Abstract: Secondary phase plays an important role in determining microstructures and properties of magnesium alloys. This paper focuses on laser-induced microstructure development and secondary phase evolution in AZ91D Mg alloy studied by SEM, TEM and EDS analyses. Compared to bulk shape and lamellar structure of the secondary phase in as-received cast material, rapid-solidified microstructures with various morphologies including nano-precipitates were observed in laser melt zone. Formation mechanisms of microstructural evolution and effect of phase development on surface properties were further discussed

Oilseed cultivars developed from induced mutations and mutations altering fatty acid composition

International Nuclear Information System (INIS)

Bhatia, C.R.; Nichterlein, K.; Maluszynski, M.

1999-01-01

One hundred and sixty-three cultivars of annual oilseed crops, developed using induced mutations, have been officially approved and released for cultivation in 26 countries. The maximum number of cultivars have been released in soybean (58), followed by groundnut (44), sesame (16), linseed (15), rapeseed (14), Indian mustard (8), castorbean (4), white mustard (3) and sunflower (1). The majority (118 of 163) of the cultivars have been developed as direct mutants and 45 of 163 by using the induced mutants in a crossing programme. While in soybean 53 out of 58 cultivars were selected as direct mutants, in groundnut 22 from 44 were developed after hybridization. Eighty-three cultivars were developed directly by exposing seeds to gamma or X-rays. Attempts have been made to infer the successful dose range, defined as the range which led to the development, registration and release of the maximum number of mutant cultivars for gamma and X-rays. The successful dose ranges in Gy for the main oilseed crops are: soybean 100-200, groundnut 150-250, rapeseed 600-800, Indian mustard 700 and sesame 100-200. The main characteristics of the new cultivars, besides higher yield, are altered plant type, early flowering and maturity and oil content. Mutants altering fatty acid composition have been isolated in soybean, rapeseed, sunflower, linseed and minor oil crops. New cultivars having altered fatty acid composition have been released in rapeseed, sunflower and linseed. The latter, previously grown for non-edible oil, has been converted to a new edible oil crop. (author)

Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development.

Science.gov (United States)

Kim, Seonwook; Yang, Lihua; Kim, Seongu; Lee, Richard G; Graham, Mark J; Berliner, Judith A; Lusis, Aldons J; Cai, Lei; Temel, Ryan E; Rateri, Debra L; Lee, Sangderk

2017-01-01

The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin II (AngII, 1,000ng/kg/min) for the last 4 weeks of ASO administration. We confirmed that the HB-EGF ASO administration significantly downregulated HB-EGF expression in multiple tissues including the liver. Importantly, the HB-EGF ASO administration significantly suppressed development of aortic aneurysms including thoracic and abdominal types. Interestingly, the HB-EGF ASO administration induced a remarkable anti-hyperlipidemic effect by suppressing very low density lipoprotein (VLDL) level in the blood. Mechanistically, the HB-EGF targeting suppressed hepatic VLDL secretion rate without changing heparin-releasable plasma triglyceride (TG) hydrolytic activity or fecal neutral cholesterol excretion rate. This result suggested that the HB-EGF targeting induced protection against aneurysm development through anti-hyperlipidemic effects. Suppression of hepatic VLDL production process appears to be a key mechanism for the anti-hyperlipidemic effects by the HB-EGF targeting.

The Groningen Radiotherapy-Induced Xerostomia questionnaire : Development and validation of a new questionnaire

NARCIS (Netherlands)

Beetz, I.; Burlage, Fred; Bijl, H.P.; Chouvalova, Olga; Christianen, M.E.; Vissink, A.; van der Laan, B.F.; de Bock, G.H.; Langendijk, J.A.

2010-01-01

Purpose: The purpose of this study was to develop and validate a questionnaire (Groningen Radiotherapy-Induced Xerostomia (GRIX) questionnaire) that has the ability to distinguish between patient-rated xerostomia during day and night and can be used to evaluate the impact of emerging radiation

Cell death induced by gamma irradiation of developing skeletal muscle

International Nuclear Information System (INIS)

Olive, M.; Blanco, R.; Rivera, R.; Cinos, C.; Ferrer, I.

1995-01-01

Newborn Sprague-Dawley rats were exposed to a single dose of 2 Gy gamma rays and killed from 6 h to 5 d later. Increased numbers of dying cells, characterised by their extreme chromatin condensation and often nuclear fragmentation were seen in skeletal muscle 6 h after irradiation. Dying cells decreased to nearly normal values 48 h later. In situ labelling of nuclear DNA fragmentation identified individual cells bearing fragmented DNA. The effects of gamma rays were suppressed following cycloheximide i.p. at a dose of 1 μg/g body weight given at the time of irradiation. Taken together, the present morphological and pharmacological results suggest that gamma ray induced cell death in skeletal muscle is apoptotic, and that the process is associated with protein synthesis. Finally, proliferating cell nuclear antigen-immunoreactive cells, which were abundant in control rats, decreased in number 48 h after irradiation. However, a marked increase significantly above normal age values was observed at the 5th day, thus suggesting that regeneration occurs following irradiation-induced cell death in developing muscle. (author)

Radio-induced fibrosis of skin: contribution to its development and treatment

International Nuclear Information System (INIS)

Vozenin-Brotons, Marie-Catherine

1999-01-01

Fibrosis of skin is frequently observed after therapeutic and accidental irradiations, and is characterized by the appearance of activated fibroblasts called myo-fibroblasts and the accumulation of extracellular matrix compounds. We postulated that radiation fibrosis could be considered as a chronic scar, where constant production of activating signals are emitted, whereas no negative feed back regulation occur. However, recent studies demonstrated that radiation-induced fibrosis could be treated using therapeutic agents like the superoxide dismutase. In order to better understand the mechanisms leading to skin fibrosis, we studied both the early reactions and the late fibrotic tissue induced by high radiation doses in normal skin. In particular, we investigated in the role of growth factors in these reactions. The synthesis of TGF-β1 was found to be increased, both the epidermis and the dermis, immediately after irradiation. This overexpression sustained during the development and the persistence phases of fibrosis, suggesting that the immediate cellular response induce a cascade of activation for genes and proteins which will result in the late effect of radiation in skin. Furthermore, these observations showed that the TGF-β1 could be a target for anti-fibrotic treatment. In order to test this hypothesis and to investigate further in the mechanisms leading to fibrosis regression after SOD treatment, we develop normal and fibrosis-like reconstructed skin models. These reconstructed skins were treated with liposomal and carrier-free Cu/Zn SOD, and examined for their effects on cell number, apoptosis and phenotypic differentiation. The results showed that SOD did not induce myo-fibroblast cell death or apoptosis whereas it significantly reduced TGF-β1 expression, thus demonstrating that SOD might be considered as a potent antagonist of the major fibro-genic growth factor. We also found that SOD significantly lowered the levels of the myo-fibroblast marker �

Development of laser-induced fluorescence detection to assay DNA damage

International Nuclear Information System (INIS)

Sharma, M.; Freund, H.G.

1991-01-01

A precolumn derivation method has been developed for high performance liquid chromatographic (HPLC) analysis of DNA damage using fluorescence detection. The modified nucleotide, having excised enzymatically from the exposed DNA, is enriched from the normal nucleotides and labeled with a fluorescent reagent. The labeling procedure involves phosphoramidation of the nucleotide with ethylenediamine (EDA) followed by conjugation of the free amino end of the phosphoramidate with 5-dimethylaminonaphthalene 1-sulfonyl chloride, commonly known as Dansyl chloride. The dansylated nucleotide can be analyzed with a sub-picomole limit of detection (LOD) by conventional HPLC using a conventional fluorescence detector. By combining microbore HPLC with laser-induced fluorescence (LIF) detection, the authors present the development of an analytical system that has sub-femtomole LOD for real-time analysis of the dansylated nucleotide. In this paper the application of the developed system in fluorescence postlabeling assay of a small alkyl-modified nucleotide (5-methyl CMP) in calf-thymus DNA is discussed

Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

International Nuclear Information System (INIS)

Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

2010-01-01

Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17β-estradiol (E 2 ). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E 2 -induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E 2 pellets, co-exposure to quercetin did not protect rats from E 2 -induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E 2 -treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E 2 group relative to those in the E 2 group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F 2α (8-iso-PGF 2α ) levels as a marker of oxidant stress showed that quercetin did not decrease E 2 -induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E 2 -induced oxidant stress and may exacerbate breast carcinogenesis in E 2 -treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E 2 and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E 2 and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E 2 -induced

Seismic Parameters of Mining-Induced Aftershock Sequences for Re-entry Protocol Development

Science.gov (United States)

Vallejos, Javier A.; Estay, Rodrigo A.

2018-03-01

A common characteristic of deep mines in hard rock is induced seismicity. This results from stress changes and rock failure around mining excavations. Following large seismic events, there is an increase in the levels of seismicity, which gradually decay with time. Restricting access to areas of a mine for enough time to allow this decay of seismic events is the main approach in re-entry strategies. The statistical properties of aftershock sequences can be studied with three scaling relations: (1) Gutenberg-Richter frequency magnitude, (2) the modified Omori's law (MOL) for the temporal decay, and (3) Båth's law for the magnitude of the largest aftershock. In this paper, these three scaling relations, in addition to the stochastic Reasenberg-Jones model are applied to study the characteristic parameters of 11 large magnitude mining-induced aftershock sequences in four mines in Ontario, Canada. To provide guidelines for re-entry protocol development, the dependence of the scaling relation parameters on the magnitude of the main event are studied. Some relations between the parameters and the magnitude of the main event are found. Using these relationships and the scaling relations, a space-time-magnitude re-entry protocol is developed. These findings provide a first approximation to concise and well-justified guidelines for re-entry protocol development applicable to the range of mining conditions found in Ontario, Canada.

Deficient PKR in RAX/PKR Association Ameliorates Ethanol-Induced Neurotoxicity in the Developing Cerebellum.

Science.gov (United States)

Li, Hui; Chen, Jian; Qi, Yuanlin; Dai, Lu; Zhang, Mingfang; Frank, Jacqueline A; Handshoe, Jonathan W; Cui, Jiajun; Xu, Wenhua; Chen, Gang

2015-08-01

Ethanol-induced neuronal loss is closely related to the pathogenesis of fetal alcohol spectrum disorders. The cerebellum is one of the brain areas that are most sensitive to ethanol. The mechanism underlying ethanol neurotoxicity remains unclear. Our previous in vitro studies have shown that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) regulates neuronal apoptosis upon ethanol exposure and ethanol activates PKR through association with its intracellular activator RAX. However, the role of PKR and its interaction with RAX in vivo have not been investigated. In the current study, by utilizing N-PKR-/- mice, C57BL/6J mice with a deficient RAX-binding domain in PKR, we determined the critical role of RAX/PKR association in PKR-regulated ethanol neurotoxicity in the developing cerebellum. Our data indicate that while N-PKR-/- mice have a similar BAC profile as wild-type mice, ethanol induces less brain/body mass reduction as well as cerebellar neuronal loss. In addition, ethanol promotes interleukin-1β (IL-1β) secretion, and IL-1β is a master cytokine regulating inflammatory response. Importantly, ethanol-promoted IL-1β secretion is inhibited in the developing cerebellum of N-PKR-/- mice. Thus, RAX/PKR interaction and PKR activation regulate ethanol neurotoxicity in the developing cerebellum, which may involve ethanol-induced neuroinflammation. Further, PKR could be a possible target for pharmacological intervention to prevent or treat fetal alcohol spectrum disorder (FASD).

Diet-induced obesity promotes colon tumor development in azoxymethane-treated mice.

Directory of Open Access Journals (Sweden)

Iina Tuominen

Full Text Available Obesity is an important risk factor for colon cancer in humans, and numerous studies have shown that a high fat diet enhances colon cancer development. As both increased adiposity and high fat diet can promote tumorigenesis, we examined the effect of diet-induced obesity, without ongoing high fat diet, on colon tumor development. C57BL/6J male mice were fed regular chow or high fat diet for 8 weeks. Diets were either maintained or switched resulting in four experimental groups: regular chow (R, high fat diet (H, regular chow switched to high fat diet (RH, and high fat diet switched to regular chow (HR. Mice were then administered azoxymethane to induce colon tumors. Tumor incidence and multiplicity were dramatically smaller in the R group relative to all groups that received high fat diet at any point. The effect of obesity on colon tumors could not be explained by differences in aberrant crypt foci number. Moreover, diet did not alter colonic expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, interleukin-1β, and interferon-γ, which were measured immediately after azoxymethane treatment. Crypt apoptosis and proliferation, which were measured at the same time, were increased in the HR relative to all other groups. Our results suggest that factors associated with obesity - independently of ongoing high fat diet and obesity - promote tumor development because HR group animals had significantly more tumors than R group, and these mice were fed the same regular chow throughout the entire carcinogenic period. Moreover, there was no difference in the number of aberrant crypt foci between these groups, and thus the effect of obesity appears to be on subsequent stages of tumor development when early preneoplastic lesions transition into adenomas.

Increased transgenerational epigenetic variation, but not predictable epigenetic variants, after environmental exposure in two apomictic dandelion lineages

NARCIS (Netherlands)

Preite, Veronica; Oplaat, Carla; Biere, Arjen; Kirschner, Jan; van der Putten, Wim H; Verhoeven, Koen J F

DNA methylation is one of the mechanisms underlying epigenetic modifications. DNA methylations can be environmentally induced and such induced modifications can at times be transmitted to successive generations. However, it remains speculative how common such environmentally induced

Increased transgenerational epigenetic variation, but not predictable epigenetic variants, after environmental exposure in two apomictic dandelion lineages

NARCIS (Netherlands)

Preite, Veronica; Oplaat, Carla; Biere, Arjen; Kirschner, Jan; Putten, van der Wim H.; Verhoeven, Koen J.F.

2018-01-01

DNA methylation is one of the mechanisms underlying epigenetic modifications. DNA methylations can be environmentally induced and such induced modifications can at times be transmitted to successive generations. However, it remains speculative how common such environmentally induced

Development of Probabilistic Flood Inundation Mapping For Flooding Induced by Dam Failure

Science.gov (United States)

Tsai, C.; Yeh, J. J. J.

2017-12-01

A primary function of flood inundation mapping is to forecast flood hazards and assess potential losses. However, uncertainties limit the reliability of inundation hazard assessments. Major sources of uncertainty should be taken into consideration by an optimal flood management strategy. This study focuses on the 20km reach downstream of the Shihmen Reservoir in Taiwan. A dam failure induced flood herein provides the upstream boundary conditions of flood routing. The two major sources of uncertainty that are considered in the hydraulic model and the flood inundation mapping herein are uncertainties in the dam break model and uncertainty of the roughness coefficient. The perturbance moment method is applied to a dam break model and the hydro system model to develop probabilistic flood inundation mapping. Various numbers of uncertain variables can be considered in these models and the variability of outputs can be quantified. The probabilistic flood inundation mapping for dam break induced floods can be developed with consideration of the variability of output using a commonly used HEC-RAS model. Different probabilistic flood inundation mappings are discussed and compared. Probabilistic flood inundation mappings are hoped to provide new physical insights in support of the evaluation of concerning reservoir flooded areas.

NSAID-induced gastro-duodenal bleeding: risk of development and patient management

Directory of Open Access Journals (Sweden)

A P Rebrov

2008-01-01

Full Text Available A.P. Rebrov, E.l. Koshkina, A.A. Antonyan, R.V. Lyakisheva NSAID-induced gastro-duodenal bleeding: risk of development and patient management. Retrospective analysis of gastro-duodenal bleeding (GDB report forms was performed. Pts admitted to the department of internal diseases of Saratov regional clinical hospital from 1999 to 2004 were included. 354 cases of GDB were recorded ( 282 from 1999 to 2001 and 72 from 2002 to 2004. Cause ofbleeding, influence of NSAID administration on appearance and relapse ofbleeding, source ofbleeding and pt management were assessed. NSAJD administration was considered trigger factor of GDB in 24% in 1999-2001 and in 18% in 2002-2004. The results of the study show some tendency to decrease of NSAID- induced gastropathy frequency among causes of GDB. The main risk factors ofbleeding during NSAID treatment were age of more than 30 years, ulcer history, the first month of NSAID administration. GDB frequency did not depend on regularity of treatment and NSAID dosage.

Development and validation of a dynamic outcome prediction model for paracetamol-induced acute liver failure

DEFF Research Database (Denmark)

Bernal, William; Wang, Yanzhong; Maggs, James

2016-01-01

: The models developed here show very good discrimination and calibration, confirmed in independent datasets, and suggest that many patients undergoing transplantation based on existing criteria might have survived with medical management alone. The role and indications for emergency liver transplantation......BACKGROUND: Early, accurate prediction of survival is central to management of patients with paracetamol-induced acute liver failure to identify those needing emergency liver transplantation. Current prognostic tools are confounded by recent improvements in outcome independent of emergency liver...... transplantation, and constrained by static binary outcome prediction. We aimed to develop a simple prognostic tool to reflect current outcomes and generate a dynamic updated estimation of risk of death. METHODS: Patients with paracetamol-induced acute liver failure managed at intensive care units in the UK...

Parent-of-origin and trans-generational germline influences on behavioral development: the interacting roles of mothers, fathers, and grandparents.

Science.gov (United States)

Curley, J P; Mashoodh, R

2010-05-01

Mothers and fathers do not contribute equally to the development of their offspring. In addition to the differential investment of mothers versus fathers in the rearing of offspring, there are also a number of germline factors that are transmitted unequally from one parent or the other that contribute significantly to offspring development. This article shall review four major sources of such parent-of-origin effects. Firstly, there is increasing evidence that genes inherited on the sex chromosomes including the nonpseudoautosomal part of the Y chromosome that is only inherited from fathers to sons, contribute to brain development and behavior independently of the organizing effects of sex hormones. Secondly, recent work has demonstrated that mitochondrial DNA that is primarily inherited only from mothers may play a much greater than anticipated role in neurobehavioral development. Thirdly, there exists a class of genes known as imprinted genes that are epigenetically silenced when passed on in a parent-of-origin specific manner and have been shown to regulate brain development and a variety of behaviors. Finally, there is converging evidence from several disciplines that environmental variations experienced by mothers and fathers may lead to plasticity in the development and behavior of offspring and that this phenotypic inheritance can be solely transmitted through the germline. Mechanistically, this may be achieved through altered programming within germ cells of the epigenetic status of particular genes such as retrotransposons and imprinted genes or potentially through altered expression of RNAs within gametes.

ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

National Research Council Canada - National Science Library

Rosenstein, Barry S

2005-01-01

The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced subcutaneous late tissue morbidity possess a variant allele in the ATM gene compared...

ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

National Research Council Canada - National Science Library

Rosenstein, Barry S

2006-01-01

The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced subcutaneous late tissue morbidity possess a variant allele in the ATM gene compared...

Toward development of an in vitro model of methamphetamine-induced dopamine nerve terminal toxicity.

Science.gov (United States)

Kim, S; Westphalen, R; Callahan, B; Hatzidimitriou, G; Yuan, J; Ricaurte, G A

2000-05-01

To develop an in vitro model of methamphetamine (METH)-induced dopamine (DA) neurotoxicity, striatal synaptosomes were incubated at 37 degrees C with METH for different periods of time (10-80 min), washed once, then tested for DA transporter function at 37 degrees C. METH produced time- and dose-dependent reductions in the V(max) of DA uptake, without producing any change in K(m). Incubation of synaptosomes with the DA neurotoxins 1-methyl-4-phenyl-pyridinium ion, 6-hydroxydopamine, and amphetamine under similar conditions produced comparable effects. In contrast, incubation with fenfluramine, a serotonin neurotoxin, did not. METH-induced decreases in DA uptake were selective, insofar as striatal glutamate uptake was unaffected. Various DA transporter blockers (cocaine, methylphenidate, and bupropion) afforded complete protection against METH-induced decreases in DA uptake, without producing any effect themselves. METH's effects were also temperature dependent, with greater decreases in DA uptake occurring at higher temperatures. Tests for residual drug revealed small amounts (0.1-0.2 microM) of remaining METH, but kinetic studies indicated that decreases in DA uptake were not likely to be due to METH acting as a competitive inhibitor of DA uptake. Decreases in the V(max) of DA uptake were not accompanied by decreases in B(max) of [(3)H]WIN 35,428 binding, possibly because there is no mechanism for removing damaged DA nerve endings from the in vitro preparation Collectively, these results give good support to the development of a valid in vitro model that may prove helpful for elucidating the mechanisms underlying METH-induced DA neurotoxicity.

Influence of the Elastic Dilatation of Mining-Induced Unloading Rock Mass on the Development of Bed Separation

Directory of Open Access Journals (Sweden)

Weibing Zhu

2018-03-01

Full Text Available Understanding how mining-induced strata movement, fractures, bed separation, and ground subsidence evolve is an area of great importance for the underground coal mining industry, particularly for disaster control and sustainable mining. Based on the rules of mining-induced strata movement and stress evolution, accumulative dilatation of mining-induced unloading rock mass is first proposed in this paper. Triaxial unloading tests and theoretical calculation were used to investigate the influence of elastic dilatation of mining-induced unloading rock mass on the development of bed separation in the context of district No. 102 where a layer of super-thick igneous sill exists in the Haizi colliery. It is shown that the elastic dilatation coefficient of mining-induced unloading hard rocks and coal were 0.9~1.0‰ and 2.63‰ respectively under the axial load of 16 MPa, which increased to 1.30~1.59‰ and 4.88‰ when the axial load was 32 MPa. After successively excavating working faces No. 1022 and No. 1024, the elastic dilatation of unloading rock mass was 157.9 mm, which represented approximately 6.3% of the mining height, indicating the elastic dilatation of mining-induced unloading rock mass has a moderate influence on the development of bed separation. Drill hole detection results after grouting, showed that only 0.33 m of the total grouting filling thickness (1.67 m was located in the fracture zone and bending zone, which verified the result from previous drill hole detection that only small bed separation developed beneath the igneous sill. Therefore, it was concluded that the influences of elastic dilatation of mining-induced unloading rock mass and bulking of caved rock mass jointly contributed to the small bed separation space beneath the igneous sill. Since the accurate calculation of the unloading dilatation of rock mass is the fundamental basis for quantitative calculation of bed separation and surface subsidence, this paper is expected

Elevated paternal glucocorticoid exposure modifies memory retention in female offspring.

Science.gov (United States)

Yeshurun, Shlomo; Rogers, Jake; Short, Annabel K; Renoir, Thibault; Pang, Terence Y; Hannan, Anthony J

2017-09-01

Recent studies have demonstrated that behavioral traits are subject to transgenerational modification by paternal environmental factors. We previously reported on the transgenerational influences of increased paternal stress hormone levels on offspring anxiety and depression-related behaviors. Here, we investigated whether offspring sociability and cognition are also influenced by paternal stress. Adult C57BL/6J male mice were treated with corticosterone (CORT; 25mg/L) for four weeks prior to paired-matings to generate F1 offspring. Paternal CORT treatment was associated with decreased body weights of female offspring and a marked reduction of the male offspring. There were no differences in social behavior of adult F1 offspring in the three-chamber social interaction test. Despite male offspring of CORT-treated fathers displaying hyperactivity in the Y-maze, there was no observable difference in short-term spatial working memory. Spatial learning and memory testing in the Morris water maze revealed that female, but not male, F1 offspring of CORT-treated fathers had impaired memory retention. We used our recently developed methodology to analyze the spatial search strategy of the mice during the learning trials and determined that the impairment could not be attributed to underlying differences in search strategy. These results provide evidence for the impact of paternal corticosterone administration on offspring cognition and complement the cumulative knowledge of transgenerational epigenetic inheritance of acquired traits in rodents and humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Epigenetic regulation leading to induced pluripotency drives cancer development in vivo

Energy Technology Data Exchange (ETDEWEB)

Ohnishi, Kotaro [Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507 (Japan); Department of Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194 (Japan); Semi, Katsunori [Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507 (Japan); Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8507 (Japan); Yamada, Yasuhiro, E-mail: y-yamada@cira.kyoto-u.ac.jp [Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507 (Japan); Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8507 (Japan)

2014-12-05

Highlights: • Epigenetic regulation of failed reprogramming-associated cancer cells is discussed. • Similarity between pediatric cancer and reprogramming-associated cancer is discussed. • Concept for epigenetic cancer is discussed. - Abstract: Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by the transient expression of reprogramming factors. During the reprogramming process, somatic cells acquire the ability to undergo unlimited proliferation, which is also an important characteristic of cancer cells, while their underlying DNA sequence remains unchanged. Based on the characteristics shared between pluripotent stem cells and cancer cells, the potential involvement of the factors leading to reprogramming toward pluripotency in cancer development has been discussed. Recent in vivo reprogramming studies provided some clues to understanding the role of reprogramming-related epigenetic regulation in cancer development. It was shown that premature termination of the in vivo reprogramming result in the development of tumors that resemble pediatric cancers. Given that epigenetic modifications play a central role during reprogramming, failed reprogramming-associated cancer development may have provided a proof of concept for epigenetics-driven cancer development in vivo.

Epigenetic regulation leading to induced pluripotency drives cancer development in vivo

International Nuclear Information System (INIS)

Ohnishi, Kotaro; Semi, Katsunori; Yamada, Yasuhiro

2014-01-01

Highlights: • Epigenetic regulation of failed reprogramming-associated cancer cells is discussed. • Similarity between pediatric cancer and reprogramming-associated cancer is discussed. • Concept for epigenetic cancer is discussed. - Abstract: Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by the transient expression of reprogramming factors. During the reprogramming process, somatic cells acquire the ability to undergo unlimited proliferation, which is also an important characteristic of cancer cells, while their underlying DNA sequence remains unchanged. Based on the characteristics shared between pluripotent stem cells and cancer cells, the potential involvement of the factors leading to reprogramming toward pluripotency in cancer development has been discussed. Recent in vivo reprogramming studies provided some clues to understanding the role of reprogramming-related epigenetic regulation in cancer development. It was shown that premature termination of the in vivo reprogramming result in the development of tumors that resemble pediatric cancers. Given that epigenetic modifications play a central role during reprogramming, failed reprogramming-associated cancer development may have provided a proof of concept for epigenetics-driven cancer development in vivo

A Prospective Cohort Study on Radiation-induced Hypothyroidism: Development of an NTCP Model

International Nuclear Information System (INIS)

Boomsma, Marjolein J.; Bijl, Hendrik P.; Christianen, Miranda E.M.C.; Beetz, Ivo; Chouvalova, Olga; Steenbakkers, Roel J.H.M.; Laan, Bernard F.A.M. van der; Wolffenbuttel, Bruce H.R.; Oosting, Sjoukje F.; Schilstra, Cornelis; Langendijk, Johannes A.

2012-01-01

Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism. Methods and Materials: The thyroid-stimulating hormone (TSH) level of 105 patients treated with (chemo-) radiation therapy for head-and-neck cancer was prospectively measured during a median follow-up of 2.5 years. Hypothyroidism was defined as elevated serum TSH with decreased or normal free thyroxin (T4). A multivariate logistic regression model with bootstrapping was used to determine the most important prognostic variables for radiation-induced hypothyroidism. Results: Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroid gland dose and the thyroid gland volume, was most predictive for radiation-induced hypothyroidism. NTCP values increased with higher mean thyroid gland dose (odds ratio [OR]: 1.064/Gy) and decreased with higher thyroid gland volume (OR: 0.826/cm 3 ). Model performance was good with an area under the curve (AUC) of 0.85. Conclusions: This is the first prospective study resulting in an NTCP model for radiation-induced hypothyroidism. The probability of hypothyroidism rises with increasing dose to the thyroid gland, whereas it reduces with increasing thyroid gland volume.

A Prospective Cohort Study on Radiation-induced Hypothyroidism: Development of an NTCP Model

Energy Technology Data Exchange (ETDEWEB)

Boomsma, Marjolein J.; Bijl, Hendrik P.; Christianen, Miranda E.M.C.; Beetz, Ivo; Chouvalova, Olga; Steenbakkers, Roel J.H.M. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Laan, Bernard F.A.M. van der [Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Wolffenbuttel, Bruce H.R. [Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Oosting, Sjoukje F. [Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Schilstra, Cornelis [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A., E-mail: j.a.langendijk@umcg.nl [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

2012-11-01

Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism. Methods and Materials: The thyroid-stimulating hormone (TSH) level of 105 patients treated with (chemo-) radiation therapy for head-and-neck cancer was prospectively measured during a median follow-up of 2.5 years. Hypothyroidism was defined as elevated serum TSH with decreased or normal free thyroxin (T4). A multivariate logistic regression model with bootstrapping was used to determine the most important prognostic variables for radiation-induced hypothyroidism. Results: Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroid gland dose and the thyroid gland volume, was most predictive for radiation-induced hypothyroidism. NTCP values increased with higher mean thyroid gland dose (odds ratio [OR]: 1.064/Gy) and decreased with higher thyroid gland volume (OR: 0.826/cm{sup 3}). Model performance was good with an area under the curve (AUC) of 0.85. Conclusions: This is the first prospective study resulting in an NTCP model for radiation-induced hypothyroidism. The probability of hypothyroidism rises with increasing dose to the thyroid gland, whereas it reduces with increasing thyroid gland volume.

The characters and developments of therapy and research of neutron-induced acute radiation sickness

International Nuclear Information System (INIS)

Wang Xinru; Luo Qingliang; Wang Baoqing; Dong Shukui

2003-01-01

Neutron radiation will exert seriously lesions on body and lead to acute radiation sickness (ARS). Neutron induced ARS is characterized by complicated symptoms of gastrointestinal, high earlier death rate and lacking of specially therapeutic approaches. The primarily curable method is to treat patients with comprehensive means such as anti-infection, anti-bleeding and blood infusion, et. Cytokines can improve the hematopoietic functions of bone marrow. With the rapid development of the molecular biology and the emergence of cytokines such as recombinant human interleukin-11 that could help the regeneration of the gastrointestinal mucosa, neutron-induced ARS will be treated with new methods

'Abasin-95', a new oilseed rape cultivar developed through induced mutations

International Nuclear Information System (INIS)

Shah, S.A.; Ali, I.; Rahman, K.

2001-01-01

Brassica oilseeds are the second most important source of vegetable oil in Pakistan. Due to the low priority attached to these to these crops in the past, no systematic breeding work was undertaken to develop improved varieties of rapeseed/mustard, resulting in a narrow genetic base of these crops. At the Nuclear Institute for Food and Agriculture (NIFA), gamma radiation was used to induce genetic variability in traits of economic importance thus diversifying the genetic base of indigenous/exotic cultivars of Brassica oilseeds

Aggression, Anxiety, and Social Development in Adolescent Children of War Veterans with PTSD Versus those of Non-Veterans

Directory of Open Access Journals (Sweden)

Gh Ahmadzadeh

2004-10-01

Full Text Available Background: Evaluation of psychological problems in children of war veterans with PTSD can be the first step in improving the war – related trauma and interrupting the known phenomenon of transgeneration transmission of this trauma. Methods: Using three self – administered questionnaires, this study was carried out to compare aggression, anxiety, and social development (as some of the most expected mental health problems in this group according to literature in adolescent children of war veterans and those of non-veterans. The two groups were matched regarding sex, academic achievement, stage of education, and economic status of the family. Results: After controlling the level of parental education (as a confounding variable, a higher rate of aggression and anxiety was found in adolescent children of war veterans with PTSD but the two groups showed no significant difference in social development. Conclusion: The higher rate of anxiety and aggression among children of war veterans with PTSD along with many other factors such as low socioeconomic status in this group signifies the importance of mental health screening programs and appropriate interventions in this group. Keywords: Aggression, Social Development, Anxiety, War Veterans, PTSD, Adolescent.

Development and modelisation of a hydro-power conversion system based on vortex induced vibration

Science.gov (United States)

Lefebure, David; Dellinger, Nicolas; François, Pierre; Mosé, Robert

2016-11-01

The Vortex Induced Vibration (VIV) phenomenon leads to mechanical issues concerning bluff bodies immerged in fluid flows and have therefore been studied by numerous authors. Moreover, an increasing demand for energy implies the development of alternative, complementary and renewable energy solutions. The main idea of EauVIV project consists in the use of VIV rather than its deletion. When rounded objects are immerged in a fluid flow, vortices are formed and shed on their downstream side, creating a pressure imbalance resulting in an oscillatory lift. A convertor modulus consists of an elastically mounted, rigid cylinder on end-springs, undergoing flow- induced motion when exposed to transverse fluid-flow. These vortices induce cyclic lift forces in opposite directions on the circular bar and cause the cylinder to vibrate up and down. An experimental prototype was developed and tested in a free-surface water channel and is already able to recover energy from free-stream velocity between 0.5 and 1 m.s -1. However, the large number of parameters (stiffness, damping coefficient, velocity of fluid flow, etc.) associated with its performances requires optimization and we choose to develop a complete tridimensionnal numerical model solution. A 3D numerical model has been developed in order to represent the real system behavior and improve it through, for example, the addition of parallel cylinders. The numerical model build up was carried out in three phases. The first phase consists in establishing a 2D model to choose the turbulence model and quantify the dependence of the oscillations amplitudes on the mesh size. The second corresponds to a 3D simulation with cylinder at rest in first time and with vertical oscillation in a second time. The third and final phase consists in a comparison between the experimental system dynamic behavior and its numerical model.

EG-VEGF Maintenance Over Early Gestation to Develop a Pregnancy-Induced Hypertensive Animal Model.

Science.gov (United States)

Reynaud, Déborah; Sergent, Frédéric; Abi Nahed, Roland; Brouillet, Sophie; Benharouga, Mohamed; Alfaidy, Nadia

2018-01-01

During the last decade, multiple animal models have been developed to mimic hallmarks of pregnancy-induced hypertension (PIH) diseases, which include gestational hypertension, preeclampsia (PE), or eclampsia. Converging in vitro, ex vivo, and clinical studies from our group strongly suggested the potential involvement of the new angiogenic factor EG-VEGF (endocrine gland-derived-VEGF) in the development of PIH. Here, we described the protocol that served to demonstrate that maintenance of EG-VEGF production over 11.5 days post coitus (dpc) in the gravid mice caused the development of PIH. The developed model exhibited most hallmarks of preeclampsia.

Periodontitis promotes the diabetic development of obese rat via miR-147 induced classical macrophage activation.

Science.gov (United States)

Xu, Ran; Zeng, Guang; Wang, Shuyong; Tao, Hong; Ren, Le; Zhang, Zhe; Zhang, Qingna; Zhao, Jinxiu; Gao, Jing; Li, Daxu

2016-10-01

Emerging evidence has indicated the bad effect of periodontal inflammation on diabetes control. However, the exact regulatory mechanisms within the association between periodontitis and diabetic development remain unclear. This study aims to investigate the function of microRNAs in regulating periodontitis-induced inflammation in an obese rat model. Experimental periodontitis was introduced into OLETF and LETO rat. Intraperitoneal glucose tolerance test was performed to detect diabetic development. Serum cytokines levels and microRNAs expression were detected by ELISA and RT-PCR analysis respectively. And, macrophages were isolated for gain- and loss-of-function studies, to investigate the regulatory mechanism of miR-147 in periodontitis-induced inflammation. Periodontitis induced proinflammatory response with classical activated macrophages in both rats, but distinctively aggravated the impaired glucose tolerance of OLETF rat with spontaneous type 2 diabetes. Analysis for serum microRNAs expression showed the distinctive and synergistic upregulation of miR-147 with periodontitis-induced effects in rats, while further experiments demonstrated the positive regulatory mechanism of miR-147 on classical activated macrophages with overexpressed proinflammatory markers, showing M1 phenotype. This study provided new evidence for the positive effect of periodontal inflammation on diabetic development, while the regulatory mechanism of miR-147 on classical macrophage activation, was verified, and presumed to contribute to the impaired glucose tolerance aggravated by periodontitis in obese rats. Besides, this study indicated the application of miR-147 for therapeutic approach in the treatment of diabetes with periodontitis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline.

Science.gov (United States)

Ashida, Terunao; Takato, Tetsuya; Matsuzaki, Gen; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

2014-01-01

We have recently demonstrated that basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias that have been induced by electrical stimulation of the cervical vagus. This study investigated whether similar basal cardiomyopathy would develop in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds in anesthetized rabbits. Colloidal carbon was injected after adrenaline infusion. Wall movement velocity of the left ventricular base was assessed by tissue Doppler echocardiography. Animals were killed either 1 week or 3-4 weeks later. Pathological lesions were identified by deposits of carbon particles. Animals were divided into two groups according to the infused dose of adrenaline. The small-dose group (group S, n = 15) received 1-10 μg and the large-dose group (group L, n = 23) received 15-60 μg of adrenaline. Adrenaline infusion induced premature ventricular contractions followed by monomorphic ventricular tachycardias in 22 of 23 animals in group L, but in only 1 of 15 animals in group S. Wall movement velocity of the left ventricular base decreased just after adrenaline infusion, remained low after 1 week, and recovered to near-baseline levels after 3-4 weeks in group L. Unique cardiac lesions identified by deposits of carbon particles were frequently observed on the left ventricular basal portion, almost always associated with the mitral valve and papillary muscles, but were never observed in the apical area. Lesions involving all areas of the left ventricular basal portion were observed in 22 of 23 animals in group L, but in only 2 of 15 animals in group S. Basal cardiomyopathy developed in rabbits with ventricular tachycardias induced by a single injection of adrenaline.

Induced reproduction and early development histology of Oscar Astronotus ocellatus (Agassiz, 1831).

Science.gov (United States)

Paes, Maria do Carmo Faria; Makino, Lilian Cristina; Vasquez, Leonardo Avendaño; Fernandes, João Batista Kochenborger; Valentin, Fernanda Nogueira; Nakaghi, Laura Satiko Okada

2015-04-01

Oscar (Astronotus ocellatus) is an important fish from the Amazon Basin that has great potential for fish farming, human consumption, sport fishing and fish keeping. This study aimed to evaluate the effect of two hormonal treatments on the induction of artificial reproduction in broodstock and to describe the histological development of embryos and larvae. Broodstocks were selected and induced using two different hormones: (i) extract of carp pituitary (ECP); and (ii) synthetic human chorionic gonadotropin (hCG). Spawnings were transferred to hatcheries, collected at pre-established times, processed and analysed by histology. Astronotus ocellatus did not respond well to induced reproduction. From 16 couples of breeding fish, only five out of the eight females released oocytes after the hormonal action time, three with hCG and two with ECP; just one male responded positively to hCG. Oscar eggs were oval, and semi-adhesive, the yolk contained granules, and egg diameter was approximately 1.65 ± 0.057 to 1.98 ± 0.038 mm. Development from the initial collection (IC) point until the total absorption of the yolk lasted 315 h, at an average temperature of 27.45 ± 2.13°C. Several events marked embryonic and larval development, including the formation of the optic cup, forebrain, otic vesicle and cephalic divisions. The newly hatched larvae had non-pigmented eyes, and a closed mouth and anus, as well as the presence of adhesive glands on the head. Larval development was characterized by formation of the heart, liver, gaseous bladder, gills, pronephros, brain, fins and also the digestive tract. These results provide important information for the rearing and reproduction of A. ocellatus.

Development of solenoid-induced helical wiggler with four poles per period

International Nuclear Information System (INIS)

Ohigashi, N.; Tsunawaki, Y.; Kiyochi, M.; Nakao, N.; Fujita, M.; Imasaki, K.; Nakai, S.; Mima, K.

1999-01-01

A new type of helical wiggler consisting of two staggered-iron arrays inserted into a solenoid field has been developed. The field measured by a test wiggler showed linear increment with the period. It was seen that 24% of the solenoid field contributed to the induced wiggler field when the gap length and the period of the wiggler were 16 and 24 mm, respectively. This wiggler would be useful for an FEL with a low-energy electron beam propagating in a strong axial guiding field

Development of solenoid-induced helical wiggler with four poles per period

CERN Document Server

Ohigashi, N; Kiyochi, M; Nakao, N; Fujita, M; Imasaki, K; Nakai, S; Mima, K

1999-01-01

A new type of helical wiggler consisting of two staggered-iron arrays inserted into a solenoid field has been developed. The field measured by a test wiggler showed linear increment with the period. It was seen that 24% of the solenoid field contributed to the induced wiggler field when the gap length and the period of the wiggler were 16 and 24 mm, respectively. This wiggler would be useful for an FEL with a low-energy electron beam propagating in a strong axial guiding field.

Phloem development in nematode-induced feeding sites: The implications of auxin and cytokinin

Directory of Open Access Journals (Sweden)

Birgit eAbsmanner

2013-07-01

Full Text Available Sedentary plant parasitic nematodes such as root-knot nematodes and cyst nematodes induce giant cells or syncytia, respectively, in their host plant’s roots. These highly specialized structures serve as feeding sites from which exclusively the nematodes withdraw nutrients. While giant cells are symplastically isolated and obtain assimilates by transporter-mediated processes syncytia are massively connected to the phloem by plasmodesmata. To support the feeding sites and the nematode during their development, phloem is induced around syncytia and giant cells. In the case of syncytia the unloading phloem consists of sieve elements and companion cells and in the case of root knots it consists exclusively of sieve elements. We applied immunohistochemistry to identify the cells within the developing phloem that responded to auxin and cytokinin. Both feeding sites themselves did not respond to either hormone. We were able to show that in root knots an auxin response precedes the differentiation of these auxin responsive cells into phloem elements. This process appears to be independent of B-type Arabidopsis response regulators. Using additional markers for tissue identity we provide evidence that around giant cells protophloem is formed and proliferates dramatically. In contrast, the phloem around syncytia responded to both hormones. The presence of companion cells as well as hormone-responsive sieve elements suggests that metaphloem development occurs. The implication of auxin and cytokinin in the further development of the metaphloem is discussed.

Within and between generation phenotypic plasticity in trichome density of Mimulus guttatus.

Science.gov (United States)

Holeski, L M

2007-11-01

Mimulus guttatus (yellow monkeyflower) frequently produce glandular trichomes, a trait that may resist herbivory. Constitutive production of trichomes is variable both within and among populations of M. guttatus and most of this variation is genetic. This study demonstrates that damage on early leaves can induce increased trichome production on later leaves, a plastic response that is likely adaptive. Moreover, this study shows that this induction can be maternally transmitted, increasing trichome density in progeny before they experience herbivory. This transgenerational response must involve a yet undescribed epigenetic mechanism. These experiments also show genetic variation among plants in the capacity for both within and between plant generation induction. Despite the clear evolutionary importance of variation in constitutive and induced herbivory-resistance traits, few other studies have noted genetic variation in both within a plant species.

Effects of the environmental estrogenic contaminants bisphenol A and 17α-ethinyl estradiol on sexual development and adult behaviors in aquatic wildlife species

Science.gov (United States)

Bhandari, Ramji K.; Deem, Sharon L.; Holliday, Dawn K.; Jandegian, Caitlin M.; Kassotis, Christopher D.; Nagel, Susan C.; Tillitt, Donald E.; vom Saal, Frederick S.; Rosenfeld, Cheryl S.

2015-01-01

Endocrine disrupting chemicals (EDCs), including the mass-produced component of plastics, bisphenol A (BPA) are widely prevalent in aquatic and terrestrial habitats. Many aquatic species, such as fish, amphibians, aquatic reptiles and mammals, are exposed daily to high concentrations of BPA and ethinyl estradiol (EE2), estrogen in birth control pills. In this review, we will predominantly focus on BPA and EE2, well-described estrogenic EDCs. First, the evidence that BPA and EE2 are detectable in almost all bodies of water will be discussed. We will consider how BPA affects sexual and neural development in these species, as these effects have been the best characterized across taxa. For instance, such chemicals have been in many cases reported to cause sex-reversal of males to females. Even if these chemicals do not overtly alter the gonadal sex, there are indications that several EDCs might demasculinize male-specific behaviors that are essential for attracting a mate. In so doing, these chemicals may reduce the likelihood that these males reproduce. If exposed males do reproduce, the concern is that they will then be passing on compromised genetic fitness to their offspring and transmitting potential transgenerational effects through their sperm epigenome. We will thus consider how diverse epigenetic changes might be a unifying mechanism of how BPA and EE2 disrupt several processes across species. Such changes might also serve as universal species diagnostic biomarkers of BPA and other EDCs exposure. Lastly, the evidence that estrogenic EDCs-induced effects in aquatic species might translate to humans will be considered.

Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus.

Science.gov (United States)

Nguyen, Long The; Saad, Sonia; Tan, Yi; Pollock, Carol; Chen, Hui

2017-07-01

Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity. © 2017 Society for Endocrinology.

A prediction model of drug-induced ototoxicity developed by an optimal support vector machine (SVM) method.

Science.gov (United States)

Zhou, Shu; Li, Guo-Bo; Huang, Lu-Yi; Xie, Huan-Zhang; Zhao, Ying-Lan; Chen, Yu-Zong; Li, Lin-Li; Yang, Sheng-Yong

2014-08-01

Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to be considered in drug discovery. Nevertheless, current experimental methods used to evaluate drug-induced ototoxicity are often time-consuming and expensive, indicating that they are not suitable for a large-scale evaluation of drug-induced ototoxicity in the early stage of drug discovery. We thus, in this investigation, established an effective computational prediction model of drug-induced ototoxicity using an optimal support vector machine (SVM) method, GA-CG-SVM. Three GA-CG-SVM models were developed based on three training sets containing agents bearing different risk levels of drug-induced ototoxicity. For comparison, models based on naïve Bayesian (NB) and recursive partitioning (RP) methods were also used on the same training sets. Among all the prediction models, the GA-CG-SVM model II showed the best performance, which offered prediction accuracies of 85.33% and 83.05% for two independent test sets, respectively. Overall, the good performance of the GA-CG-SVM model II indicates that it could be used for the prediction of drug-induced ototoxicity in the early stage of drug discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Early perception of stink bug damage in developing seeds of field-grown soybean induces chemical defences and reduces bug attack.

Science.gov (United States)

Giacometti, Romina; Barneto, Jesica; Barriga, Lucia G; Sardoy, Pedro M; Balestrasse, Karina; Andrade, Andrea M; Pagano, Eduardo A; Alemano, Sergio G; Zavala, Jorge A

2016-08-01

Southern green stink bugs (Nezara viridula L.) invade field-grown soybean crops, where they feed on developing seeds and inject phytotoxic saliva, which causes yield reduction. Although leaf responses to herbivory are well studied, no information is available about the regulation of defences in seeds. This study demonstrated that mitogen-activated protein kinases MPK3, MPK4 and MPK6 are expressed and activated in developing seeds of field-grown soybean and regulate a defensive response after stink bug damage. Although 10-20 min after stink bug feeding on seeds induced the expression of MPK3, MPK6 and MPK4, only MPK6 was phosphorylated after damage. Herbivory induced an early peak of jasmonic acid (JA) accumulation and ethylene (ET) emission after 3 h in developing seeds, whereas salicylic acid (SA) was also induced early, and at increasing levels up to 72 h after damage. Damaged seeds upregulated defensive genes typically modulated by JA/ET or SA, which in turn reduced the activity of digestive enzymes in the gut of stink bugs. Induced seeds were less preferred by stink bugs. This study shows that stink bug damage induces seed defences, which is perceived early by MPKs that may activate defence metabolic pathways in developing seeds of field-grown soybean. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Children of mentally ill parents—a pilot study of a group intervention program

OpenAIRE

Christiansen, Hanna; Anding, Jana; Schrott, Bastian; Röhrle, Bernd

2015-01-01

Objective: The transgenerational transmission of mental disorders is one of the most prominent risk factors for the development of psychological disorders. Children of mentally ill parents are a vulnerable high risk group with overall impaired development and high rates of psychological disorders. To date there are only a few evidence based intervention programs for this group overall and hardly any in Germany. We translated the evidence based Family Talk Intervention by Beardslee (2009) and ...

Epigenetic effects of methoxychlor and vinclozolin on male gametes.

Science.gov (United States)

Paoloni-Giacobino, Ariane

2014-01-01

Imprinting is an epigenetic form of gene regulation that mediates a parent-of-origin-dependent expression of the alleles of a number of genes. Imprinting, which occurs at specific sites within or surrounding the gene, called differentially methylated domains, consists in a methylation of CpGs. The appropriate transmission of genomics imprints is essential for the control of embryonic development and fetal growth. A number of endocrine disruptors (EDs) affect male reproductive tract development and spermatogenesis. It was postulated that the genetic effects of EDs might be induced by alterations in gene imprinting. We tested two EDs: methoxychlor and vinclozolin. Their administration during gestation induced in the offspring a decrease in sperm counts and significant modifications in the methylation pattern of a selection of paternally and maternally expressed canonical imprinted genes. The observation that imprinting was largely untouched in somatic cells suggests that EDs exert their damaging effects via the process of reprogramming that is unique to gamete development. Interestingly, the effects were transgenerational, although disappearing gradually from F1 to F3. A systematic analysis showed a heterogeneity in the CpG sensitivity to EDs. We propose that the deleterious effects of EDs on the male reproductive system are mediated by imprinting defects in the sperm. The reported effects of EDs on human male spermatogenesis might be mediated by analogous imprinting alterations. © 2014 Elsevier Inc. All rights reserved.

Transgenerational Radiation Epigenetics

Science.gov (United States)

2014-11-01

Powell,C.A., Downes,S., and Terrell ,J.D. (1990). Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear...hepatocyte growth factor for non-small cell lung cancer. Ann . Thorac. Surg. 66, 1915- 1918. Tawa,R., Kimura,Y., Komura,J., Miyamura,Y., Kurishita,A

Electric Field Induced Strain in Electrostrictive Polymers Under High Hydrostatic Pressure - System Development and Material Characterization

National Research Council Canada - National Science Library

Zhang, Q

2000-01-01

... of (i) developing a high performance piezo-bimorph based dilatometer which can be used to characterize the electric field induced strain response in polymer films under high hydrostatic pressure, (ii...

Texture developed during deformation of Transformation Induced Plasticity (TRIP) steels

International Nuclear Information System (INIS)

Bhargava, M; Asim, T; Sushil, M; Shanta, C

2015-01-01

Automotive industry is currently focusing on using advanced high strength steels (AHSS) due to its high strength and formability for closure applications. Transformation Induced Plasticity (TRIP) steel is promising material for this application among other AHSS. The present work is focused on the microstructure development during deformation of TRIP steel sheets. To mimic complex strain path condition during forming of automotive body, Limit Dome Height (LDH) tests were conducted and samples were deformed in servo hydraulic press to find the different strain path. FEM Simulations were done to predict different strain path diagrams and compared with experimental results. There is a significant difference between experimental and simulation results as the existing material models are not applicable for TRIP steels. Micro texture studies were performed on the samples using EBSD and X-RD techniques. It was observed that austenite is transformed to martensite and texture developed during deformation had strong impact on limit strain and strain path. (paper)

Texture developed during deformation of Transformation Induced Plasticity (TRIP) steels

Science.gov (United States)

Bhargava, M.; Shanta, C.; Asim, T.; Sushil, M.

2015-04-01

Automotive industry is currently focusing on using advanced high strength steels (AHSS) due to its high strength and formability for closure applications. Transformation Induced Plasticity (TRIP) steel is promising material for this application among other AHSS. The present work is focused on the microstructure development during deformation of TRIP steel sheets. To mimic complex strain path condition during forming of automotive body, Limit Dome Height (LDH) tests were conducted and samples were deformed in servo hydraulic press to find the different strain path. FEM Simulations were done to predict different strain path diagrams and compared with experimental results. There is a significant difference between experimental and simulation results as the existing material models are not applicable for TRIP steels. Micro texture studies were performed on the samples using EBSD and X-RD techniques. It was observed that austenite is transformed to martensite and texture developed during deformation had strong impact on limit strain and strain path.

The effect of synthetic inducers of systemic resistance in inhibiting grey mold development on geranium and poinsettia

Directory of Open Access Journals (Sweden)

Jolanta Floryszak-Wieczorek

2013-12-01

Full Text Available Several chemical activators of resistance were tested to evaluate their efficiency in restricting development caused by Botryotinia fuckeliana (Botrytis cinerea on geranium and poinsettia leaves. The used signal pathway inducers of salicylic acid, such as DL-â-aminobutyric acid (BABA, g-aminobutyric acid (GABA and benzothiadiazole (BTH, at the applied rates markedly inhibited the development of grey mould in the both plant species. The mentioned inducers showed no toxic or restricting effect on the fungus growth and development under in vitro conditions. Only methyl jasmonate (Me-JA, a potential activator of independent signal transduction pathway, at the applied quantities (O,1-1,0 mg·ml-1, noticeably enhanced the disease spot development probably through stimulation of ethylene synthesis in plant. Me-JA added to medium with B.cinerea showed a strong antifungal action, whereas ethylene significantly stimulated mycelium growth in the in vitro cultures.

Development of prototype induced-fission-based Pu accountancy instrument for safeguards applications.

Science.gov (United States)

Seo, Hee; Lee, Seung Kyu; An, Su Jung; Park, Se-Hwan; Ku, Jeong-Hoe; Menlove, Howard O; Rael, Carlos D; LaFleur, Adrienne M; Browne, Michael C

2016-09-01

Prototype safeguards instrument for nuclear material accountancy (NMA) of uranium/transuranic (U/TRU) products that could be produced in a future advanced PWR fuel processing facility has been developed and characterized. This is a new, hybrid neutron measurement system based on fast neutron energy multiplication (FNEM) and passive neutron albedo reactivity (PNAR) methods. The FNEM method is sensitive to the induced fission rate by fast neutrons, while the PNAR method is sensitive to the induced fission rate by thermal neutrons in the sample to be measured. The induced fission rate is proportional to the total amount of fissile material, especially plutonium (Pu), in the U/TRU product; hence, the Pu amount can be calibrated as a function of the induced fission rate, which can be measured using either the FNEM or PNAR method. In the present study, the prototype system was built using six (3)He tubes, and its performance was evaluated for various detector parameters including high-voltage (HV) plateau, efficiency profiles, dead time, and stability. The system's capability to measure the difference in the average neutron energy for the FNEM signature also was evaluated, using AmLi, PuBe, (252)Cf, as well as four Pu-oxide sources each with a different impurity (Al, F, Mg, and B) and producing (α,n) neutrons with different average energies. Future work will measure the hybrid signature (i.e., FNEM×PNAR) for a Pu source with an external interrogating neutron source after enlarging the cavity size of the prototype system to accommodate a large-size Pu source (~600g Pu). Copyright © 2016 Elsevier Ltd. All rights reserved.

Induced pluripotency with endogenous and inducible genes

International Nuclear Information System (INIS)

Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

2008-01-01

The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER TAM ) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols

Developmental plasticity and epigenetic mechanisms underpinning metabolic and cardiovascular diseases.

Science.gov (United States)

Low, Felicia M; Gluckman, Peter D; Hanson, Mark A

2011-06-01

The importance of developmental factors in influencing the risk of later-life disease has a strong evidence base derived from multiple epidemiological, clinical and experimental studies in animals and humans. During early life, an organism is able to adjust its phenotypic development in response to environmental cues. Such developmentally plastic responses evolved as a fitness-maximizing strategy to cope with variable environments. There are now increasing data that these responses are, at least partially, underpinned by epigenetic mechanisms. A mismatch between the early and later-life environments may lead to inappropriate early life-course epigenomic changes that manifest in later life as increased vulnerability to disease. There is also growing evidence for the transgenerational transmission of epigenetic marks. This article reviews the evidence that susceptibility to metabolic and cardiovascular disease in humans is linked to changes in epigenetic marks induced by early-life environmental cues, and discusses the clinical, public health and therapeutic implications that arise.

Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity.

Science.gov (United States)

Kras, J V; Kartha, S; Winkelstein, B A

2015-11-01

The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Male Holtzman rats underwent painful cervical facet joint distraction (FJD) or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint's mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Losartan prevents from the formation and interferes with the development of calcium chloride-induced abdominal aortic aneurysms

International Nuclear Information System (INIS)

Yan Huimin; Cui Bing; Yang Hongzhen; Hu Zhuowei; Chen Zhong; Tang Xiaobin

2010-01-01

Objective: Abdominal aortic aneurysm (AAA), a chronic inflammatory vascular disorder, results in progressive expansion and rupture of the aorta with high mortality among the elderly. Multiple factors contribute to the pathogenesis of AAA that somehow induces aneurysmal manifestations. There are no effective drugs available currently. This study aims to find out whether losartan, an angiotensin II type 1 receptor (AT1) antagonist, can prevent and treat the CaCl 2 -induced AAA. Methods: We chose periaortic application of 0.5 mol/L CaCl 2 -induced mouse AAA model. Ultrasonographic and histological studies were conducted to evaluate the formation of AAA in mice. Results: Losartan not only protected against the formation of AAA, but also hindered the development of AAA. Losartan reduced aortic expansion and elastic lamina degradation. Conclusion: The prophylactic and therapeutic effects of losartan are associated with the regulation of vascular fibrosis and inflammation. Losartan inhibits the infiltration of inflammatory cells and decreases the expression of several cytokines in the vascular tissue of AAA. Our studies will provide insight into the pathogenesis of AAA induced by CaCl 2 and offer more evidence that losartan has a great potential for the development of therapeutic agents against AAA. (authors)

Cardio-respiratory development in bird embryos: new insights from a venerable animal model

Directory of Open Access Journals (Sweden)

Warren W. Burggren

Full Text Available ABSTRACT The avian embryo is a time-honored animal model for understanding vertebrate development. A key area of extensive study using bird embryos centers on developmental phenotypic plasticity of the cardio-respiratory system and how its normal development can be affected by abiotic factors such as temperature and oxygen availability. Through the investigation of the plasticity of development, we gain a better understanding of both the regulation of the developmental process and the embryo's capacity for self-repair. Additionally, experiments with abiotic and biotic stressors during development have helped delineate not just critical windows for avian cardio-respiratory development, but the general characteristics (e.g., timing and dose-dependence of critical windows in all developing vertebrates. Avian embryos are useful in exploring fetal programming, in which early developmental experiences have implications (usually negative later in life. The ability to experimentally manipulate the avian embryo without the interference of maternal behavior or physiology makes it particularly useful in future studies of fetal programming. The bird embryo is also a key participant in studies of transgenerational epigenetics, whether by egg provisioning or effects on the germline that are transmitted to the F1 generation (or beyond. Finally, the avian embryo is heavily exploited in toxicology, in which both toxicological testing of potential consumer products as well as the consequences of exposure to anthropogenic pollutants are routinely carried out in the avian embryo. The avian embryo thus proves useful on numerous experimental fronts as an animal model that is concurrently both of adequate complexity and sufficient simplicity for probing vertebrate cardio-respiratory development.

Melatonin protect the development of preimplantation mouse embryos from sodium fluoride-induced oxidative injury.

Science.gov (United States)

Zhao, Jiamin; Fu, Beibei; Peng, Wei; Mao, Tingchao; Wu, Haibo; Zhang, Yong

2017-09-01

Recently study shows that melatonin can protect embryos from the culture environment oxidative stress. However, the protective effect of melatonin on the mouse development of preimplantation embryos under sodium fluoride (NaF) induced oxidative stress is still unclear. Here, we showed that exposure to NaF significantly increased the reactive oxygen species (ROS) level, decreased the blastocyst formation rates, and increased the fragmentation, apoptosis and retardation of blastocysts in the development of mouse preimplantation embryos. However, the protective of melatonin remarkable increased the of blastocyst formation rates, maintained mitochondrial function and total antioxidant capacity by clearing ROS. Importantly the data showed that melatonin improved the activity of enzymatic antioxidants, including glutathione(GSH), superoxide dismutase(SOD), and malonaldehyde (MDA), and increased the expression levels of antioxidative genes. Taken together, our results indicate that melatonin prevent NaF-induced oxidative damage to mouse preimplantation embryo through down regulation of ROS level, stabilization of mitochondrial function and modulation of the activity of antioxidases and antioxidant genes. Copyright © 2017 Elsevier B.V. All rights reserved.

Gendered Representations of Fandom

DEFF Research Database (Denmark)

Gürsimsek, Ödül A

2016-01-01

Lost is a transgeneric, transmedia television drama that aired from 2004 to 2010, a period which coincided with the emergence of several participatory online Web 2.0 platforms including blogs, forums, YouTube, and Twitter. Thus, Lost audiences used various platforms to form communities and discuss...... the show. This chapter analyzes the discursive practices of audiences that compose the transgeneric audience discourse of Lost, and the tensions that arise when romance fans and science fiction/mystery fans are situated in conflicted positions regarding certain storylines. The analysis provides a critical...

Sex-biased transgenerational effect of maternal stress on ...

Indian Academy of Sciences (India)

PIYALI MISRA

2018-04-25

Apr 25, 2018 ... In rats, for example, the prenatal overexposure to a few hormones is known to ... cental metabolic functions, and delayed cortical develop- ment could underlie the .... tention and fine and gross motor impairment. J. Pediatr.

Elamipretide (SS-31 Ameliorates Isoflurane-Induced Long-Term Impairments of Mitochondrial Morphogenesis and Cognition in Developing Rats

Directory of Open Access Journals (Sweden)

Jian-Jun Yang

2017-04-01

Full Text Available Mitochondria are supposed to be involved in the early pathogenesis of general anesthesia (GA-induced neurotoxicity and long-term cognitive deficits in developing brains. However, effective pharmacologic agents targeted on mitochondria during GA exposure are lacking. This study explores the protective effects of mitochondrion-targeted antioxidant elamipretide (SS-31 on mitochondrial morphogenesis and cognition in developing rats exposed to isoflurane. Rat pups at postnatal day (PND 7 were exposed to 1.5% isoflurane for 6 h following intraperitoneal administration of elamipretide or vehicle with 30 min interval. The hippocampus was immediately removed for biochemical assays. Histopathological studies were conducted at PND 21, and behavioral tests were performed at PND 40 or 60. We found that early exposure to isoflurane caused remarkable reactive oxygen species (ROS accumulation, mitochondrial deformation and neuronal apoptosis in hippocampus. The injury occurrence ultimately gave rise to long-term cognitive deficits in developing rats. Interestingly, pretreatment with elamipretide not only provided protective effect against oxidative stress and mitochondrial damages, but also attenuated isoflurane-induced cognitive deficits. Our data support the notion that mitochondrial damage is an early and long lasting event of GA-induced injury and suggest that elamipretide might have clinically therapeutic benefits for pediatric patients undertaking GA.

Jasmonic acid carboxyl methyltransferase regulates development and herbivory-induced defense response in rice.

Science.gov (United States)

Qi, Jinfeng; Li, Jiancai; Han, Xiu; Li, Ran; Wu, Jianqiang; Yu, Haixin; Hu, Lingfei; Xiao, Yutao; Lu, Jing; Lou, Yonggen

2016-06-01

Jasmonic acid (JA) and related metabolites play a key role in plant defense and growth. JA carboxyl methyltransferase (JMT) may be involved in plant defense and development by methylating JA to methyl jasmonate (MeJA) and thus influencing the concentrations of JA and related metabolites. However, no JMT gene has been well characterized in monocotyledon defense and development at the molecular level. After we cloned a rice JMT gene, OsJMT1, whose encoding protein was localized in the cytosol, we found that the recombinant OsJMT1 protein catalyzed JA to MeJA. OsJMT1 is up-regulated in response to infestation with the brown planthopper (BPH; Nilaparvata lugens). Plants in which OsJMT1 had been overexpressed (oe-JMT plants) showed reduced height and yield. These oe-JMT plants also exhibited increased MeJA levels but reduced levels of herbivore-induced JA and jasmonoyl-isoleucine (JA-Ile). The oe-JMT plants were more attractive to BPH female adults but showed increased resistance to BPH nymphs, probably owing to the different responses of BPH female adults and nymphs to the changes in levels of H2 O2 and MeJA in oe-JMT plants. These results indicate that OsJMT1, by altering levels of JA and related metabolites, plays a role in regulating plant development and herbivore-induced defense responses in rice. © 2015 Institute of Botany, Chinese Academy of Sciences.

Myeloid Sarcoma Developing in Prexisting Hydroxyurea-Induced Leg Ulcer in a Polycythemia Vera Patient

Directory of Open Access Journals (Sweden)

Hatim Nafil

2013-01-01

Full Text Available Myeloid sarcoma (MS is an extramedullary tumour consisting of myeloblasts or immature myeloid cells located in an extramedullary site. It may occur at presentation of AML, at relapse, or prior to the onset of frank leukemia. We report a rare case of MS developing in prexisting Hydroxyurea-induced leg Ulcer in a 70-year-old woman.

Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

Directory of Open Access Journals (Sweden)

Logan Richard M

2010-03-01

Full Text Available Abstract Background Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases.

Science.gov (United States)

Cameron, Robert B; Beeson, Craig C; Schnellmann, Rick G

2016-12-08

Mitochondria have various roles in cellular metabolism and homeostasis. Because mitochondrial dysfunction is associated with many acute and chronic degenerative diseases, mitochondrial biogenesis (MB) is a therapeutic target for treating such diseases. Here, we review the role of mitochondrial dysfunction in acute and chronic degenerative diseases and the cellular signaling pathways by which MB is induced. We then review existing work describing the development and application of drugs that induce MB in vitro and in vivo. In particular, we discuss natural products and modulators of transcription factors, kinases, cyclic nucleotides, and G protein-coupled receptors.

Compatibility of a novel thrombospondin-1 analog with fertility and pregnancy in a xenograft mouse model of endometriosis.

Directory of Open Access Journals (Sweden)

Diane S Nakamura

Full Text Available Endometriosis is a gynecological disease defined by the growth of endometrium outside of the uterus. Although endometriosis contributes to 50% of female infertility cases, medical treatments are incompatible with pregnancy. Angiogenesis, the growth of blood vessels from existing vasculature, plays a crucial role in endometriotic lesion growth and survival. Previously, we demonstrated the effectiveness of thrombospondin-1 analog, ABT-898 (Abbott Laboratories to inhibit endometriotic lesion vascularization in mice. We have now evaluated the trans-generational implications of ABT-898 treatment before and during mouse pregnancy. We hypothesized that ABT-898 would target lesion vasculature without affecting pregnancy, offspring development, or ovarian and uterine vascularity in mice. Endometriosis was induced using human endometrium in β-estradiol-primed BALB/c-Rag-2-/-Il2rγ-/- mice receiving intraperitoneal injections of ABT-898 (25 mg/kg or 5% dextrose control for 21 days. Ultrasound assessment of lesion vascularization revealed a reduction in blood flow supplying treated lesions. Excised ABT-898 treated lesions stained for CD31+ endothelial cells exhibited a decrease in microvessel density. Following confirmation of estrous cycling, mice were bred and treated with ABT-898 on gestation days 7, 9, 11, 13, 15, 17, and 19. ABT-898 did not affect estrous cycling or pregnancy parameters including litter size across generations and offspring weight gain. Quantification of angiogenic cytokine plasma levels revealed no significant differences between treatment groups. Vimentin staining of the uterus and ovary revealed no observable effects of ABT-898. Similarly, no obvious histological anomalies were observed in the kidney, liver, ovary, or uterus following ABT-898 treatment. These results suggest that ABT-898 effectively inhibit endometriotic lesion vascularization without affecting trans-generational pregnancy outcomes in mice.

Radiation-induced changes of the developing nervous system of amphibians

International Nuclear Information System (INIS)

Schneider, M.

1986-01-01

The nervous system of amphibians (Xenopus laevis and Bufo) is of an outstanding sensitivity against irradiation in the early periods of its tissue induction and development. This is descriptively shown by various pathological disturbances. Irradiated series showed a protracted course of development. The brains obtains lower relative weights and diminished absolute lengths although the body weight remained nearly constant. The distribution of pigmentation in the brains of treated animals was changed. This indicated radiation-induced disturbances. Further, the significance of pigmentation pattern for a distinct evaluation of histological effects is also confirmed by a coincidence between the gross visible anomalies of the brain and the number of pigment-sites. Examples of malformation are given by aplasias, hypoplasias, hyperplasias up to cases of cyclopia. In the peripheral nervous system of Xenopus the neuromuscular junctions of the musculus interhyoideus were examined. The majority of neural endplates in the irradiated cases showed a loss of Schwann cells. As a consequence a diffusion of the transmitter acetylcholine in the endplate-region must be suggested. Accordingly, the morphological compensation reaction was seen in a thickening and sprouting. (orig.)

Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice.

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Oliveira-Lima, A J; Santos, R; Hollais, A W; Gerardi-Junior, C A; Baldaia, M A; Wuo-Silva, R; Yokoyama, T S; Costa, J L; Malpezzi-Marinho, E L A; Ribeiro-Barbosa, P C; Berro, L F; Frussa-Filho, R; Marinho, E A V

2015-04-01

Hallucinogenic drugs were used to treat alcoholic patients in the past, and recent developments in the study of hallucinogens led to a renewal of interest regarding the application of these drugs in the treatment of addiction. In this scenario, accumulating evidence suggests that the hallucinogenic brew ayahuasca (Aya) may have therapeutic effects on substance abuse problems. We investigated the effects of Aya on spontaneous locomotor activity and ethanol(Eth)-induced hyperlocomotion and subsequent locomotor sensitization by a two-injection protocol. Additionally, we tested the effect of Aya on an 8-day counter-sensitization protocol to modify sensitized responses induced by a repeated treatment with Eth (1.8g/kg) for 8 alternate days. Aya showed high sensitivity in preventing the development of Eth-induced behavioral sensitization, attenuating it at all doses (30, 100, 200, 300 or 500 mg/kg) without modifying spontaneous locomotor activity. At the highest doses (300 and 500 mg/kg), Aya also showed selectivity to both acute and sensitized Eth responses. Finally, a counter-sensitization strategy with 100 or 300 mg/kg of Aya for 8 consecutive days after the establishment of Eth-induced behavioral sensitization was effective in blocking its subsequent expression on an Eth challenge. We demonstrated that Aya not only inhibits early behaviors associated with the initiation and development of Eth addiction, but also showed effectiveness in reversing long-term drug effects expression, inhibiting the reinstatement of Eth-induced behavioral sensitization when administered in the Eth-associated environment. Copyright © 2015 Elsevier Inc. All rights reserved.

Endogenous egg immune defenses in the yellow mealworm beetle (Tenebrio molitor).

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Jacobs, Chris G C; Gallagher, Joe D; Evison, Sophie E F; Heckel, David G; Vilcinskas, Andreas; Vogel, Heiko

2017-05-01

In order to survive microbe encounters, insects rely on both physical barriers as well as local and systemic immune responses. Most research focusses on adult or larval defenses however, whereas insect eggs are also in need of protection. Lately, the defense of eggs against microbes has received an increasing amount of attention, be it through endogenous egg defenses, trans-generational immune priming (TGIP) or parental investment. Here we studied the endogenous immune response in eggs and adults of Tenebrio molitor. We show that many immune genes are induced in both adults and eggs. Furthermore, we show that eggs reach comparable levels of immune gene expression as adults. These findings show that the eggs of Tenebrio are capable of an impressive endogenous immune response, and indicate that such inducible egg defenses are likely common in insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cartilage oligomeric matrix protein deficiency promotes early onset and the chronic development of collagen-induced arthritis

DEFF Research Database (Denmark)

Geng, Hui; Carlsen, Stefan; Nandakumar, Kutty

2008-01-01

ABSTRACT: INTRODUCTION: Cartilage oligomeric matrix protein (COMP) is a homopentameric protein in cartilage. The development of arthritis, like collagen-induced arthritis (CIA), involves cartilage as a target tissue. We have investigated the development of CIA in COMP-deficient mice. METHODS: COMP......-deficient mice in the 129/Sv background were backcrossed for 10 generations against B10.Q mice, which are susceptible to chronic CIA. COMP-deficient and wild-type mice were tested for onset, incidence, and severity of arthritis in both the collagen and collagen antibody-induced arthritis models. Serum anti......-collagen II and anti-COMP antibodies as well as serum COMP levels in arthritic and wild-type mice were measured by enzyme-linked immunosorbent assay. RESULTS: COMP-deficient mice showed a significant early onset and increase in the severity of CIA in the chronic phase, whereas collagen II-antibody titers were...

Cue-induced craving among inhalant users: Development and preliminary validation of a visual cue paradigm.

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Jain, Shobhit; Dhawan, Anju; Kumaran, S Senthil; Pattanayak, Raman Deep; Jain, Raka

2017-12-01

Cue-induced craving is known to be associated with a higher risk of relapse, wherein drug-specific cues become conditioned stimuli, eliciting conditioned responses. Cue-reactivity paradigm are important tools to study psychological responses and functional neuroimaging changes. However, till date, there has been no specific study or a validated paradigm for inhalant cue-induced craving research. The study aimed to develop and validate visual cue stimulus for inhalant cue-associated craving. The first step (picture selection) involved screening and careful selection of 30 cue- and 30 neutral-pictures based on their relevance for naturalistic settings. In the second step (time optimization), a random selection of ten cue-pictures each was presented for 4s, 6s, and 8s to seven adolescent male inhalant users, and pre-post craving response was compared using a Visual Analogue Scale(VAS) for each of the picture and time. In the third step (validation), craving response for each of 30 cue- and 30 neutral-pictures were analysed among 20 adolescent inhalant users. Findings revealed a significant difference in before and after craving response for the cue-pictures, but not neutral-pictures. Using ROC-curve, pictures were arranged in order of craving intensity. Finally, 20 best cue- and 20 neutral-pictures were used for the development of a 480s visual cue paradigm. This is the first study to systematically develop an inhalant cue picture paradigm which can be used as a tool to examine cue induced craving in neurobiological studies. Further research, including its further validation in larger study and diverse samples, is required. Copyright © 2017 Elsevier B.V. All rights reserved.

On Developing Field-Effect-Tunable Nanofluidic Ion Diodes with Bipolar, Induced-Charge Electrokinetics

Directory of Open Access Journals (Sweden)

Ye Tao

2018-04-01

Full Text Available We introduce herein the induced-charge electrokinetic phenomenon to nanometer fluidic systems; the design of the nanofluidic ion diode for field-effect ionic current control of the nanometer dimension is developed by enhancing internal ion concentration polarization through electrochemical transport of inhomogeneous inducing-counterions resulting from double gate terminals mounted on top of a thin dielectric layer, which covers the nanochannel connected to microfluidic reservoirs on both sides. A mathematical model based on the fully-coupled Poisson-Nernst-Plank-Navier-Stokes equations is developed to study the feasibility of this structural configuration causing effective ionic current rectification. The effect of various physiochemical and geometrical parameters, such as the native surface charge density on the nanochannel sidewalls, the number of gate electrodes (GE, the gate voltage magnitude, and the solution conductivity, permittivity, and thickness of the dielectric coating, as well as the size and position of the GE pair of opposite gate polarity, on the resulted rectification performance of the presented nanoscale ionic device is numerically analyzed by using a commercial software package, COMSOL Multiphysics (version 5.2. Three types of electrohydrodynamic flow, including electroosmosis of 1st kind, induced-charge electroosmosis, and electroosmosis of 2nd kind that were originated by the Coulomb force within three distinct charge layers coexist in the micro/nanofluidic hybrid network and are shown to simultaneously influence the output current flux in a complex manner. The rectification factor of a contrast between the ‘on’ and ‘off’ working states can even exceed one thousand-fold in the case of choosing a suitable combination of several key parameters. Our demonstration of field-effect-tunable nanofluidic ion diodes of double external gate electrodes proves invaluable for the construction of a flexible electrokinetic platform

Formulating transgenerational technology critique as conflictual collaboration

DEFF Research Database (Denmark)

Chimirri, Niklas Alexander

2015-01-01

In the fields of technology design studies and human-computer interaction (HCI), participatory technology design involving children has been on the rise. Particularly studies applying and developing the cooperative inquiry methodology or inspired by it are of growing interest to media technology...... designers. While the underlying impetus of actively involving the intended users in the design process and thereby taking the children as seriously as adult users is laudable, the overarching framing and directionality of the technology design process is rendered unquestionable for the children....... The presentation illustrates that the pristine intention of engaging in intergenerational technology design is potentially helpful for collectively formulating a productive and sustainable technology critique. On the downside the applied methodologies lack viable concepts for meaningfully analyzing its...

Post-irradiation dietary vitamin E does not affect the development of radiation-induced lung damage in rats

International Nuclear Information System (INIS)

Wiegman, Erwin M.; Gameren, Mieke M. van; Kampinga, Harm H.; Szabo, Ben G.; Coppes, Rob P.

2004-01-01

The purpose of this study was to investigate whether application of post-irradiation vitamin E, an anti-oxidant, could prevent the development of radiation induced lung damage. Wistar rats were given vitamin E enriched or vitamin E deprived food starting from 4 weeks after 18 Gy single dose irradiation of the right thorax. Neither breathing frequencies nor CT density measurements revealed differences between the groups. It is concluded that post-irradiation vitamin E does not influence radiation-induced fibrosis to the lung

Depleted uranium induces sex- and tissue-specific methylation patterns in adult zebrafish

International Nuclear Information System (INIS)

Gombeau, Kewin; Pereira, Sandrine; Ravanat, Jean-Luc; Camilleri, Virginie; Cavalie, Isabelle; Bourdineaud, Jean-Paul; Adam-Guillermin, Christelle

2016-01-01

We examined the effects of chronic exposure to different concentrations (2 and 20 μg L"−"1) of environmentally relevant waterborne depleted uranium (DU) on the DNA methylation patterns both at HpaII restriction sites (5′-CCGG-3′) and across the whole genome in the zebrafish brain, gonads, and eyes. We first identified sex-dependent differences in the methylation level of HpaII sites after exposure. In males, these effects were present as early as 7 days after exposure to 20 μg L"−"1 DU, and were even more pronounced in the brain, gonads, and eyes after 24 days. However, in females, hypomethylation was only observed in the gonads after exposure to 20 μg L"−"1 DU for 24 days. Sex-specific effects of DU were also apparent at the whole-genome level, because in males, exposure to 20 μg L"−"1 DU for 24 days resulted in cytosine hypermethylation in the brain and eyes and hypomethylation in the gonads. In contrast, in females, hypermethylation was observed in the brain after exposure to both concentrations of DU for 7 days. Based on our current knowledge of uranium toxicity, several hypotheses are proposed to explain these findings, including the involvement of oxidative stress, alteration of demethylation enzymes and the calcium signaling pathway. This study reports, for the first time, the sex- and tissue-specific epigenetic changes that occur in a nonhuman organism after exposure to environmentally relevant concentrations of uranium, which could induce transgenerational epigenetic effects. - Highlights: • This study demonstrates a sex-related effect of DU exposure on DNA methylation patterns. • Impacts on DNA methylation patterns revealed a tissue-specific effect of DU exposure. • The MS–AFLP and HPLC–MS/MS sensitively and complementarily demonstrated the responses to environmental concentrations of DU.

Detection of expressional changes induced by intrauterine growth restriction in the developing rat pancreas.

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Zhang, Lin; Chen, Wei; Dai, Yuee; Zhu, Ziyang; Liu, Qianqi

2016-07-01

Intrauterine growth retardation (IUGR) is a disorder that can result in permanent changes in the physiology and metabolism of the newborn, which increased the risk of disease in adulthood. Evidence supports IUGR as a risk factor for the development of diabetes mellitus, which could reflect changes in pancreas developmental pathways. We sought to characterize the IUGR-induced alterations of the complex pathways of pancreas development in a rat model of IUGR. We analyzed the pancreases of Sprague Dawley rats after inducing IUGR by feeding a maternal low calorie diet from gestational day 1 until term. IUGR altered the pancreatic structure, islet areas, and islet quantities and resulted in abnormal morphological changes during pancreatic development, as determined by HE staining and light microscopy. We identified multiple differentially expressed genes in the pancreas by RT-PCR. The genes of the insulin/FoxO1/Pdx1/MafA signaling pathway were first expressed at embryonic day 14 (E14). The expressions of insulin and MafA increased as the fetus grew while the expressions of FoxO1 and Pdx1 decreased. Compared with the control rats, the expressions of FoxO1, Pdx1, and MafA were lower in the IUGR rats, whereas insulin levels showed no change. Microarray profiling, in combination with quantitative real-time PCR, uncovered a subset of microRNAs that changed in their degree of expression throughout pancreatic development. In conclusion, our data support the hypothesis that IUGR influences the development of the rat pancreas. We also identified new pathways that appear to be programmed by IUGR. © 2016 by the Society for Experimental Biology and Medicine.

Protective effects of resveratrol on ethanol-induced apoptosis in embryonic stem cells and disruption of embryonic development in mouse blastocysts

International Nuclear Information System (INIS)

Huang, L.-H.; Shiao, N.-H.; Hsuuw, Y.-D.; Chan, W.-H.

2007-01-01

Previous studies have established that ethanol induces apoptosis, but the precise molecular mechanisms are currently unclear. Here, we show that 0.3-1.0% (w/v) ethanol induces apoptosis in mouse blastocysts and that resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties, prevents ethanol-induced apoptosis and inhibition of cell proliferation. Moreover, ethanol-treated blastocysts show normal levels of implantation on culture dishes in vitro but a reduced ability to reach the later stages of embryonic development. Pretreatment with resveratrol prevented ethanol-induced disruption of embryonic development in vitro and in vivo. In an in vitro cell-based assay, we further found that ethanol increases the production of reactive oxygen species in ESC-B5 embryonic stem cells, leading to an increase in the intracellular concentrations of cytoplasmic free Ca 2+ and NO, loss of mitochondrial membrane potential, mitochondrial release of cytochrome c, activation of caspase-9 and -3, and apoptosis. These changes were blocked by pretreatment with resveratrol. Based on these results, we propose a model for the protective effect of resveratrol on ethanol-induced cell injury in blastocysts and ESC-B5 cells

Radiation-induced apoptosis in undifferentiated cells of the developing brain as a biological defense mechanism

International Nuclear Information System (INIS)

Inouye, Minioru; Tamaru, Masao.

1994-01-01

Undifferentiated neural (UN) cells of the developing mammalian brain are highly sensitive to the lethal effects of ionizing radiation. Nuclear and cytoplasmic condensation, transglutaminase activation, and internucleosomal DNA cleavage reveal radiation-induced cell death in the ventricular zone of the cerebral mantle and external granular layer of the cerebellum to be due to apoptosis. A statistically significant increase of cell mortality can be induced by 0.03 Gy X-irradiation, and the mortality increases linearly with increasing doses. It is not changed by split doses, probably because of the very slow repair of cellular damage and a lack of adaptive response. Although extensive apoptosis in the UN cell population results in microcephaly and mental retardation, it possesses the ability to recover from a considerable cell loss and to form the normal structure of the central nervous system. The number of cell deaths needed to induce tissue adnormalities in the adult murine brain rises in the range of 15-25% of the germinal cell population; with the threshold doses at about 0.3 Gy for cerebral anomalies and 1 Gy for cerebellar abnormalities. Threshold level is similarly suggested in prenatally exposed A-bomb survivors. High radiosensitivity of UN cells is assumed to be a manifestation of the ability of the cell to commit suicide when injured. Repeated replication of DNA and extensive gene expression are required in future proliferation and differentiation. Once an abnormality in DNA was induced and fixed in the UN cell, it would be greatly amplified and prove a danger in producing malformations and tumors. These cells would thus commit suicide for the benefit of the individual to eliminate their acquired genetic abnormalities rather than make DNA repair. UN cells in the developing brain are highly radiosensitive and readily involved in apoptosis. Paradoxically, however, this may be to protect individuals against teratogenesis and tumorigenesis. (J.P.N.)

Radiation-induced apoptosis in undifferentiated cells of the developing brain as a biological defense mechanism

Energy Technology Data Exchange (ETDEWEB)

Inouye, Minioru [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine; Tamaru, Masao

1994-12-31

Undifferentiated neural (UN) cells of the developing mammalian brain are highly sensitive to the lethal effects of ionizing radiation. Nuclear and cytoplasmic condensation, transglutaminase activation, and internucleosomal DNA cleavage reveal radiation-induced cell death in the ventricular zone of the cerebral mantle and external granular layer of the cerebellum to be due to apoptosis. A statistically significant increase of cell mortality can be induced by 0.03 Gy X-irradiation, and the mortality increases linearly with increasing doses. It is not changed by split doses, probably because of the very slow repair of cellular damage and a lack of adaptive response. Although extensive apoptosis in the UN cell population results in microcephaly and mental retardation, it possesses the ability to recover from a considerable cell loss and to form the normal structure of the central nervous system. The number of cell deaths needed to induce tissue adnormalities in the adult murine brain rises in the range of 15-25% of the germinal cell population; with the threshold doses at about 0.3 Gy for cerebral anomalies and 1 Gy for cerebellar abnormalities. Threshold level is similarly suggested in prenatally exposed A-bomb survivors. High radiosensitivity of UN cells is assumed to be a manifestation of the ability of the cell to commit suicide when injured. Repeated replication of DNA and extensive gene expression are required in future proliferation and differentiation. Once an abnormality in DNA was induced and fixed in the UN cell, it would be greatly amplified and prove a danger in producing malformations and tumors. These cells would thus commit suicide for the benefit of the individual to eliminate their acquired genetic abnormalities rather than make DNA repair. UN cells in the developing brain are highly radiosensitive and readily involved in apoptosis. Paradoxically, however, this may be to protect individuals against teratogenesis and tumorigenesis. (J.P.N.).

Maternal Sevoflurane Exposure Causes Abnormal Development of Fetal Prefrontal Cortex and Induces Cognitive Dysfunction in Offspring

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Ruixue Song

2017-01-01

Full Text Available Maternal sevoflurane exposure during pregnancy is associated with increased risk for behavioral deficits in offspring. Several studies indicated that neurogenesis abnormality may be responsible for the sevoflurane-induced neurotoxicity, but the concrete impact of sevoflurane on fetal brain development remains poorly understood. We aimed to investigate whether maternal sevoflurane exposure caused learning and memory impairment in offspring through inducing abnormal development of the fetal prefrontal cortex (PFC. Pregnant mice at gestational day 15.5 received 2.5% sevoflurane for 6 h. Learning function of the offspring was evaluated with the Morris water maze test at postnatal day 30. Brain tissues of fetal mice were subjected to immunofluorescence staining to assess differentiation, proliferation, and cell cycle dynamics of the fetal PFC. We found that maternal sevoflurane anesthesia impaired learning ability in offspring through inhibiting deep-layer immature neuron output and neuronal progenitor replication. With the assessment of cell cycle dynamics, we established that these effects were mediated through cell cycle arrest in neural progenitors. Our research has provided insights into the cell cycle-related mechanisms by which maternal sevoflurane exposure can induce neurodevelopmental abnormalities and learning dysfunction and appeals people to consider the neurotoxicity of anesthetics when considering the benefits and risks of nonobstetric surgical procedures.

Development of an NDIR CO₂ sensor-based system for assessing soil toxicity using substrate-induced respiration.

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Kaur, Jasmeen; Adamchuk, Viacheslav I; Whalen, Joann K; Ismail, Ashraf A

2015-02-26

The eco-toxicological indicators used to evaluate soil quality complement the physico-chemical criteria employed in contaminated site remediation, but their cost, time, sophisticated analytical methods and in-situ inapplicability pose a major challenge to rapidly detect and map the extent of soil contamination. This paper describes a sensor-based approach for measuring potential (substrate-induced) microbial respiration in diesel-contaminated and non-contaminated soil and hence, indirectly evaluates their microbial activity. A simple CO2 sensing system was developed using an inexpensive non-dispersive infrared (NDIR) CO2 sensor and was successfully deployed to differentiate the control and diesel-contaminated soils in terms of CO2 emission after glucose addition. Also, the sensor system distinguished glucose-induced CO2 emission from sterile and control soil samples (p ≤ 0.0001). Significant effects of diesel contamination (p ≤ 0.0001) and soil type (p ≤ 0.0001) on glucose-induced CO2 emission were also found. The developed sensing system can provide in-situ evaluation of soil microbial activity, an indicator of soil quality. The system can be a promising tool for the initial screening of contaminated environmental sites to create high spatial density maps at a relatively low cost.

Intrinsic vs. extrinsic influences on life history expression: metabolism and parentally induced temperature influences on embryo development rate

Science.gov (United States)

Martin, Thomas E.; Ton, Riccardo; Nikilson, Alina

2013-01-01

Intrinsic processes are assumed to underlie life history expression and trade-offs, but extrinsic inputs are theorised to shift trait expression and mask trade-offs within species. Here, we explore application of this theory across species. We do this based on parentally induced embryo temperature as an extrinsic input, and mass-specific embryo metabolism as an intrinsic process, underlying embryonic development rate. We found that embryonic metabolism followed intrinsic allometry rules among 49 songbird species from temperate and tropical sites. Extrinsic inputs via parentally induced temperatures explained the majority of variation in development rates and masked a relationship with metabolism; metabolism explained a minor proportion of the variation in development rates among species, and only after accounting for temperature effects. We discuss evidence that temperature further obscures the expected interspecific trade-off between development rate and offspring quality. These results demonstrate the importance of considering extrinsic inputs to trait expression and trade-offs across species.

Development of breeding materials in rice by use of induced mutation

International Nuclear Information System (INIS)

Amano, Etsuo

1988-01-01

On this 25th Gamma Field Symposium, it may be worth while to review the world situation of mutation breeding, the possibility expected to mutation methods suggested by the ever progressing genetics in rice plant, and some of the activities in the Institute of Radiation Breeding. By the help of a small computer, the key word search analysis of 'Mutation Breeding Newsletter and Mutation Breeding Review' was tried, and the results are included in this review to see the present status. The studies on artificially induced mutation suggested that the possibility of dominant mutation is less. It might be probable that the inactivation of genes is the mechanism of mutation. Still the possibility of using mutation breeding techniques for many genetic characters was suggested. After the experience for 25 years, detailed genetical and fine structure analyses became important. The studies on the expression of mutant phenotypes including molecular genetics will help to develop radiation breeding into an effective means to enrich the genetic resources for breeding. The situation in the world, the genes reported in rice, the possibility to induce useful mutants against environmental stress, the mutation in the protein content in grains, the mutants of storage carbohydrate, the possibility to widen gene resources and so on are reported. (Kako, I.)

Effects of the environmental estrogenic contaminants bisphenol A and 17α-ethinyl estradiol on sexual development and adult behaviors in aquatic wildlife species.

Science.gov (United States)

Bhandari, Ramji K; Deem, Sharon L; Holliday, Dawn K; Jandegian, Caitlin M; Kassotis, Christopher D; Nagel, Susan C; Tillitt, Donald E; Vom Saal, Frederick S; Rosenfeld, Cheryl S

2015-04-01

Endocrine disrupting chemicals (EDCs), including the mass-produced component of plastics, bisphenol A (BPA) are widely prevalent in aquatic and terrestrial habitats. Many aquatic species, such as fish, amphibians, aquatic reptiles and mammals, are exposed daily to high concentrations of BPA and ethinyl estradiol (EE2), estrogen in birth control pills. In this review, we will predominantly focus on BPA and EE2, well-described estrogenic EDCs. First, the evidence that BPA and EE2 are detectable in almost all bodies of water will be discussed. We will consider how BPA affects sexual and neural development in these species, as these effects have been the best characterized across taxa. For instance, such chemicals have been in many cases reported to cause sex-reversal of males to females. Even if these chemicals do not overtly alter the gonadal sex, there are indications that several EDCs might demasculinize male-specific behaviors that are essential for attracting a mate. In so doing, these chemicals may reduce the likelihood that these males reproduce. If exposed males do reproduce, the concern is that they will then be passing on compromised genetic fitness to their offspring and transmitting potential transgenerational effects through their sperm epigenome. We will thus consider how diverse epigenetic changes might be a unifying mechanism of how BPA and EE2 disrupt several processes across species. Such changes might also serve as universal species diagnostic biomarkers of BPA and other EDCs exposure. Lastly, the evidence that estrogenic EDCs-induced effects in aquatic species might translate to humans will be considered. Copyright © 2014 Elsevier Inc. All rights reserved.

Investigation on the effect of developed product and new food for radiation-induced skin damage

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Ho; Kim, Jong Chun; Bae, Chun Sik; Kim, Se Ra; Lee, Hae Jun; Bang, Dae Won; Lee, Jin Hee; Kim, Joong Sun; Ki, Sun Ah; Song, Myung Seop [Chonnam National University, Gwangju (Korea, Republic of)

2007-07-15

In vivo evaluation of the developed pilot product on the skin protection against UV irradiation and screening of new candidate materials. Project Results are Establishment of experimental methods for 3 morphological indices of UV-induced skin damages -Establishment of experimental methods for whitening effect evaluation -Evaluation of HemoHIM administration on the skin damage indices -Evaluation of HemoHIM skin application on the skin damage indices -Evaluation of HemoTonic administration on the skin damage indices -Evaluation of HemoTonic skin application on the skin damage indices -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 1 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 2 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 3 -Evaluation of HemoHIM on the antiinflamatory effects in the TNBS-induced colitis -Evaluation of HemoHIM on the anti-wrinkle effects in the skin -Evaluation of HemoHIM on the protective effects on the skin tissue (epidermal thickening, dermal cellularity, dermal cyst) -Evaluation of HemoHIM on the protective effects on the skin tumor development

Investigation on the effect of developed product and new food for radiation-induced skin damage

International Nuclear Information System (INIS)

Kim, Sung Ho; Kim, Jong Chun; Bae, Chun Sik; Kim, Se Ra; Lee, Hae Jun; Bang, Dae Won; Lee, Jin Hee; Kim, Joong Sun; Ki, Sun Ah; Song, Myung Seop

2007-07-01

In vivo evaluation of the developed pilot product on the skin protection against UV irradiation and screening of new candidate materials. Project Results are Establishment of experimental methods for 3 morphological indices of UV-induced skin damages -Establishment of experimental methods for whitening effect evaluation -Evaluation of HemoHIM administration on the skin damage indices -Evaluation of HemoHIM skin application on the skin damage indices -Evaluation of HemoTonic administration on the skin damage indices -Evaluation of HemoTonic skin application on the skin damage indices -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 1 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 2 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 3 -Evaluation of HemoHIM on the antiinflamatory effects in the TNBS-induced colitis -Evaluation of HemoHIM on the anti-wrinkle effects in the skin -Evaluation of HemoHIM on the protective effects on the skin tissue (epidermal thickening, dermal cellularity, dermal cyst) -Evaluation of HemoHIM on the protective effects on the skin tumor development

Involvement of high mobility group box 1 in the development and maintenance of chemotherapy-induced peripheral neuropathy in rats

International Nuclear Information System (INIS)

Nishida, Takeshi; Tsubota, Maho; Kawaishi, Yudai; Yamanishi, Hiroki; Kamitani, Natsuki; Sekiguchi, Fumiko; Ishikura, Hiroyasu; Liu, Keyue; Nishibori, Masahiro; Kawabata, Atsufumi

2016-01-01

Given that high mobility group box 1 (HMGB1), a nuclear protein, once released to the extracellular space, promotes nociception, we asked if inactivation of HMGB1 prevents or reverses chemotherapy-induced painful neuropathy in rats and also examined possible involvement of Toll-like receptor 4 (TLR4) and the receptor for advanced glycation endproduct (RAGE), known as targets for HMGB1. Painful neuropathy was produced by repeated i.p. administration of paclitaxel or vincristine in rats. Nociceptive threshold was determined by the paw pressure method and/or von Frey test in the hindpaw. Tissue protein levels were determined by immunoblotting. Repeated i.p. administration of the anti-HMGB1-neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, prevented the development of hyperalgesia and/or allodynia induced by paclitaxel or vincristine in rats. A single i.p. or intraplantar (i.pl.) administration of the antibody or rhsTM reversed the chemotherapy-induced neuropathy. A single i.pl. administration of a TLR4 antagonist or low molecular weight heparin, known to inhibit RAGE, attenuated the hyperalgesia caused by i.pl. HMGB1 and also the chemotherapy-induced painful neuropathy. Paclitaxel or vincristine treatment significantly decreased protein levels of HMGB1 in the dorsal root ganglia, but not sciatic nerves. HMGB1 thus participates in both development and maintenance of chemotherapy-induced painful neuropathy, in part through RAGE and TLR4. HMGB1 inactivation is considered useful to prevent and treat the chemotherapy-induced painful neuropathy.

Hoxa9 and Hoxa10 induce CML myeloid blast crisis development through activation of Myb expression.

Science.gov (United States)

Negi, Vijay; Vishwakarma, Bandana A; Chu, Su; Oakley, Kevin; Han, Yufen; Bhatia, Ravi; Du, Yang

2017-11-17

Mechanisms underlying the progression of Chronic Myeloid Leukemia (CML) from chronic phase to myeloid blast crisis are poorly understood. Our previous studies have suggested that overexpression of SETBP1 can drive this progression by conferring unlimited self-renewal capability to granulocyte macrophage progenitors (GMPs). Here we show that overexpression of Hoxa9 or Hoxa10 , both transcriptional targets of Setbp1 , is also sufficient to induce self-renewal of primary myeloid progenitors, causing their immortalization in culture. More importantly, both are able to cooperate with BCR/ABL to consistently induce transformation of mouse GMPs and development of aggressive leukemias resembling CML myeloid blast crisis, suggesting that either gene can drive CML progression by promoting the self-renewal of GMPs. We further identify Myb as a common critical target for Hoxa9 and Hoxa10 in inducing self-renewal of myeloid progenitors as Myb knockdown significantly reduced colony-forming potential of myeloid progenitors immortalized by the expression of either gene. Interestingly, Myb is also capable of immortalizing primary myeloid progenitors in culture and cooperating with BCR/ABL to induce leukemic transformation of mouse GMPs. Significantly increased levels of MYB transcript also were detected in all human CML blast crisis samples examined over chronic phase samples, further suggesting the possibility that MYB overexpression may play a prevalent role in driving human CML myeloid blast crisis development. In summary, our results identify overexpression of HOXA9 , HOXA10 , and MYB as critical drivers of CML progression, and suggest MYB as a key therapeutic target for inhibiting the self-renewal of leukemia-initiating cells in CML myeloid blast crisis patients.

Midkine inhibits inducible regulatory T cell differentiation by suppressing the development of tolerogenic dendritic cells.

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Sonobe, Yoshifumi; Li, Hua; Jin, Shijie; Kishida, Satoshi; Kadomatsu, Kenji; Takeuchi, Hideyuki; Mizuno, Tetsuya; Suzumura, Akio

2012-03-15

Midkine (MK), a heparin-binding growth factor, reportedly contributes to inflammatory diseases, including Crohn's disease and rheumatoid arthritis. We previously showed that MK aggravates experimental autoimmune encephalomyelitis (EAE) by decreasing regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs), a population that regulates the development of autoimmune responses, although the precise mechanism remains uncertain. In this article, we show that MK produced in inflammatory conditions suppresses the development of tolerogenic dendritic cells (DCregs), which drive the development of inducible Treg. MK suppressed DCreg-mediated expansion of the CD4(+)CD25(+)Foxp3(+) Treg population. DCregs expressed significantly higher levels of CD45RB and produced significantly less IL-12 compared with conventional dendritic cells. However, MK downregulated CD45RB expression and induced IL-12 production by reducing phosphorylated STAT3 levels via src homology region 2 domain-containing phosphatase-2 in DCreg. Inhibiting MK activity with anti-MK RNA aptamers, which bind to the targeted protein to suppress the function of the protein, increased the numbers of CD11c(low)CD45RB(+) dendritic cells and Tregs in the draining lymph nodes and suppressed the severity of EAE, an animal model of multiple sclerosis. Our results also demonstrated that MK was produced by inflammatory cells, in particular, CD4(+) T cells under inflammatory conditions. Taken together, these results suggest that MK aggravates EAE by suppressing DCreg development, thereby impairing the Treg population. Thus, MK is a promising therapeutic target for various autoimmune diseases.

The effect of food hardness on the development of dental caries in alloxan-induced diabetic rats.

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Nakahara, Yutaka; Sano, Tomoya; Kodama, Yasushi; Ozaki, Kiyokazu; Matsuura, Tetsuro

2013-01-01

We have previously shown that dental caries may be produced in diabetic rodent models fed with noncariogenic standard diets; however, many studies usually add large amounts of sugar to the diet to induce dental caries. Moreover, the physical properties of cariogenic diets have been reported as an important factor in the formation of caries. The aim of this study was to clarify the effect of the hardness of non-cariogenic diets on the development of dental caries in diabetic rodents. Seven-week-old female F344 rats were divided into 4 groups: intact rats fed with a standard pelletized or powdered diet and alloxan-induced diabetic rats fed with a standard pelletized or powdered diet. All of the rats were sacrificed at 52 weeks of age for morphological examinations on their dental tissue. Dental caries had developed and extended to all the molars in the diabetic rats that were fed with both the pelletized and powdered diets. Moreover, the lesion was significantly enhanced in the powdered diet group compared to that in the pelletized diet group. In conclusion, food hardness is an important factor influencing the development of dental caries in diabetic rats.

The Effect of Food Hardness on the Development of Dental Caries in Alloxan-Induced Diabetic Rats

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Yutaka Nakahara

2013-01-01

Full Text Available We have previously shown that dental caries may be produced in diabetic rodent models fed with noncariogenic standard diets; however, many studies usually add large amounts of sugar to the diet to induce dental caries. Moreover, the physical properties of cariogenic diets have been reported as an important factor in the formation of caries. The aim of this study was to clarify the effect of the hardness of non-cariogenic diets on the development of dental caries in diabetic rodents. Seven-week-old female F344 rats were divided into 4 groups: intact rats fed with a standard pelletized or powdered diet and alloxan-induced diabetic rats fed with a standard pelletized or powdered diet. All of the rats were sacrificed at 52 weeks of age for morphological examinations on their dental tissue. Dental caries had developed and extended to all the molars in the diabetic rats that were fed with both the pelletized and powdered diets. Moreover, the lesion was significantly enhanced in the powdered diet group compared to that in the pelletized diet group. In conclusion, food hardness is an important factor influencing the development of dental caries in diabetic rats.

Prasugrel suppresses development of lithium-induced nephrogenic diabetes insipidus in mice.

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Zhang, Yue; Peti-Peterdi, János; Brandes, Anna U; Riquier-Brison, Anne; Carlson, Noel G; Müller, Christa E; Ecelbarger, Carolyn M; Kishore, Bellamkonda K

2017-06-01

Previously, we localized ADP-activated P2Y 12 receptor (R) in rodent kidney and showed that its blockade by clopidogrel bisulfate (CLPD) attenuates lithium (Li)-induced nephrogenic diabetes insipidus (NDI). Here, we evaluated the effect of prasugrel (PRSG) administration on Li-induced NDI in mice. Both CLPD and PRSG belong to the thienopyridine class of ADP receptor antagonists. Groups of age-matched adult male B6D2 mice (N = 5/group) were fed either regular rodent chow (CNT), or with added LiCl (40 mmol/kg chow) or PRSG in drinking water (10 mg/kg bw/day) or a combination of LiCl and PRSG for 14 days and then euthanized. Water intake and urine output were determined and blood and kidney tissues were collected and analyzed. PRSG administration completely suppressed Li-induced polydipsia and polyuria and significantly prevented Li-induced decreases in AQP2 protein abundance in renal cortex and medulla. However, PRSG either alone or in combination with Li did not have a significant effect on the protein abundances of NKCC2 or NCC in the cortex and/or medulla. Immunofluorescence microscopy revealed that PRSG administration prevented Li-induced alterations in cellular disposition of AQP2 protein in medullary collecting ducts. Serum Li, Na, and osmolality were not affected by the administration of PRSG. Similar to CLPD, PRSG administration had no effect on Li-induced increase in urinary Na excretion. However, unlike CLPD, PRSG did not augment Li-induced increase in urinary arginine vasopressin (AVP) excretion. Taken together, these data suggest that the pharmacological inhibition of P2Y 12 -R by the thienopyridine group of drugs may potentially offer therapeutic benefits in Li-induced NDI.

Development and Characterization of VEGF165-Chitosan Nanoparticles for the Treatment of Radiation-Induced Skin Injury in Rats

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Daojiang Yu

2016-10-01

Full Text Available Radiation-induced skin injury, which remains a serious concern in radiation therapy, is currently believed to be the result of vascular endothelial cell injury and apoptosis. Here, we established a model of acute radiation-induced skin injury and compared the effect of different vascular growth factors on skin healing by observing the changes of microcirculation and cell apoptosis. Vascular endothelial growth factor (VEGF was more effective at inhibiting apoptosis and preventing injury progression than other factors. A new strategy for improving the bioavailability of vascular growth factors was developed by loading VEGF with chitosan nanoparticles. The VEGF-chitosan nanoparticles showed a protective effect on vascular endothelial cells, improved the local microcirculation, and delayed the development of radioactive skin damage.

Induced Seismicity

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Keranen, Katie M.; Weingarten, Matthew

2018-05-01

The ability of fluid-generated subsurface stress changes to trigger earthquakes has long been recognized. However, the dramatic rise in the rate of human-induced earthquakes in the past decade has created abundant opportunities to study induced earthquakes and triggering processes. This review briefly summarizes early studies but focuses on results from induced earthquakes during the past 10 years related to fluid injection in petroleum fields. Study of these earthquakes has resulted in insights into physical processes and has identified knowledge gaps and future research directions. Induced earthquakes are challenging to identify using seismological methods, and faults and reefs strongly modulate spatial and temporal patterns of induced seismicity. However, the similarity of induced and natural seismicity provides an effective tool for studying earthquake processes. With continuing development of energy resources, increased interest in carbon sequestration, and construction of large dams, induced seismicity will continue to pose a hazard in coming years.

The role of amino acids on the development of radiation-induced damage of central nervous system

International Nuclear Information System (INIS)

Yamatodani, Atsushi; Yamamoto, Kouichi; Nohara, Kyoko; Moriyasu, Saeko; Yamamoto, Takashi

2005-01-01

Radiation impairs some functions of the central nervous system, which is one of the radiation-resistant tissues in the body. However, the underlying mechanisms are still unclear. In this study, we investigated the effects of the effects of high-linear energy transfer (LET) heavy-ions on the release of glutamate, the major excitatory neurotransmitter in the central nervous system, in the hypothalamus of rats measured by in vivo brain microdialysis. Total body and head, but not abdominal, heavy-ion (carbon) irradiation induced a significant increase in glutamate levels to approximately 150% of the basal level at 1.5 h of the irradiation, and the release gradually increased during the observation period. Furthermore, heavy-ion-induced glutamate release was suppressed by pretreatment with the dexamethasone. These results suggested that the central pathways (i.e. the neuronal damage of the brain or inflammatory cytokines which were produced in the brain) are involved in the development of high-LET radiation-induced glutamate release. (author)

Development of a cell-based reporter assay for screening of inhibitors of hypoxia-inducible factor 2-induced gene expression.

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Woldemichael, Girma M; Vasselli, James R; Gardella, Roberta S; McKee, Tawnya C; Linehan, W Marston; McMahon, James B

2006-09-01

Reporter cell lines have been developed for the identification of inhibitors of gene expression enhanced by hypoxia-inducible factor 2, which has been implicated as a transcription factor involved in the tumorigenesis of clear cell renal carcinoma. Stably transformed reporter clones of the human renal clear cell carcinoma cell line 786-O were generated by transfection or retroviral infection. Luciferase reporter expression in the vectors used was driven by either the natural human vascular endothelial growth factor (VEGF) promoter-enhancer or by the VEGF and the human endothelial nitric oxide synthase enhancers modulating minimal human cytomegalovirus promoter. Utility of the generated reporter cell lines was validated by introducing the von Hippel-Lindau protein complex and testing for reporter inducibility by hypoxia. The dynamic range in reporter activity under hypoxic stress was found to be at least 30- to 40-fold, with a signal-to-noise ratio of 60:1. Properties of the cell lines such as tolerance to up to 3% DMSO, signal stability with multiple in vitro passages, and utility in both 96- and 384-well plate formats indicated their suitability for use in a high-throughput screen. In addition, the potential use of these reporter lines in the evaluation of high-throughput screening hits in vivo in various mice models has been demonstrated.

Involvement of hypothalamic cyclooxygenase-2, interleukin-1β and melanocortin in the development of docetaxel-induced anorexia in rats.

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Yamamoto, Kouichi; Asano, Keiko; Ito, Yui; Matsukawa, Naoki; Kim, Seikou; Yamatodani, Atsushi

2012-12-16

Docetaxel, a taxane derivative, is frequently used for the treatment of advanced breast cancer, non-small cell lung cancer, and metastatic prostate cancer. Clinical reports demonstrated that docetaxel-based chemotherapy often induces anorexia, but the etiology is not completely understood. To elucidate possible mechanisms, we investigated the involvement of central interleukin (IL)-1β, cyclooxygenase (COX)-2, and pro-opiomelanocortin (POMC) in the development of docetaxel-induced anorexia in rats. Rats received docetaxel (10mg/kg, i.p.) with or without pretreatment with selective COX-2 inhibitors, NS-398 (10 and 30 mg/kg, i.g.) or celecoxib (10 and 30 mg/kg, i.g.), and a non-selective COX inhibitor, indomethacin (10mg/kg, i.g.), then food intake was monitored for 24h after administration. We also examined expression of IL-1β, COX-2, and POMC mRNA in hypothalamus of docetaxel-treated rats and the effect of a COX-2 inhibitor on docetaxel-induced POMC mRNA expression. Food consumption in rats was significantly decreased 24h after administration of docetaxel and anorexia was partially reversed by all COX inhibitors. Administration of docetaxel increased IL-1β, COX-2, and POMC mRNA expression in the hypothalamus of rats. The time required to increase these gene expressions was comparable to the latency period of docetaxel-induced anorexia in rats. In addition, pretreatment with COX-2 inhibitors suppressed docetaxel-induced expression of POMC mRNA. These results suggest that IL-1β and COX-2 mRNA expression and subsequent activation of POMC in the hypothalamus may contribute to the development of docetaxel-induced anorexia in rats. Copyright © 2012. Published by Elsevier Ireland Ltd.

A New Rat Model of Epileptic Spasms Based on Methylazoxymethanol-Induced Malformations of Cortical Development

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Eun-Hee Kim

2017-06-01

Full Text Available Malformations of cortical development (MCDs can cause medically intractable epilepsies and cognitive disabilities in children. We developed a new model of MCD-associated epileptic spasms by treating rats prenatally with methylazoxymethanol acetate (MAM to induce cortical malformations and postnatally with N-methyl-d-aspartate (NMDA to induce spasms. To produce cortical malformations to infant rats, two dosages of MAM (15 mg/kg, intraperitoneally were injected to pregnant rats at gestational day 15. In prenatally MAM-exposed rats and the controls, spasms were triggered by single (6 mg/kg on postnatal day 12 (P12 or 10 mg/kg on P13 or 15 mg/kg on P15 or multiple doses (P12, P13, and P15 of NMDA. In prenatally MAM-exposed rats with single NMDA-provoked spasms at P15, we obtain the intracranial electroencephalography and examine the pretreatment response to adrenocorticotropic hormone (ACTH or vigabatrin. Rat pups prenatally exposed to MAM exhibited a significantly greater number of spasms in response to single and multiple postnatal NMDA doses than vehicle-exposed controls. Vigabatrin treatment prior to a single NMDA dose on P15 significantly suppressed spasms in MAM group rats (p < 0.05, while ACTH did not. The MAM group also showed significantly higher fast oscillation (25–100 Hz power during NMDA-induced spasms than controls (p = 0.047. This new model of MCD-based epileptic spasms with corresponding features of human spasms will be valuable for future research of the developmental epilepsy.

Low Level Laser Therapy Reduces the Development of Lung Inflammation Induced by Formaldehyde Exposure.

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Cristiane Miranda da Silva

Full Text Available Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA, an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1% or vehicle (distillated water during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure. Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant.

Boundary-layer development and transition due to free-stream exothermic reactions in shock-induced flows

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Hall, J. L.

1974-01-01

A study of the effect of free-stream thermal-energy release from shock-induced exothermic reactions on boundary-layer development and transition is presented. The flow model is that of a boundary layer developing behind a moving shock wave in two-dimensional unsteady flow over a shock-tube wall. Matched sets of combustible hydrogen-oxygen-nitrogen mixtures and inert hydrogen-nitrogen mixtures were used to obtain transition data over a range of transition Reynolds numbers from 1,100,000 to 21,300,000. The heat-energy is shown to significantly stabilize the boundary layer without changing its development character. A method for application of this data to flat-plate steady flows is included.

The Development of Genetics in the Light of Thomas Kuhn's Theory of Scientific Revolutions.

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Portin, Petter

2015-01-01

The concept of a paradigm is in the key position in Thomas Kuhn's theory of scientific revolutions. A paradigm is the framework within which the results, concepts, hypotheses and theories of scientific research work are understood. According to Kuhn, a paradigm guides the working and efforts of scientists during the time period which he calls the period of normal science. Before long, however, normal science leads to unexplained matters, a situation that then leads the development of the scientific discipline in question to a paradigm shift--a scientific revolution. When a new theory is born, it has either gradually emerged as an extension of the past theory, or the old theory has become a borderline case in the new theory. In the former case, one can speak of a paradigm extension. According to the present author, the development of modern genetics has, until very recent years, been guided by a single paradigm, the Mendelian paradigm which Gregor Mendel launched 150 years ago, and under the guidance of this paradigm the development of genetics has proceeded in a normal fashion in the spirit of logical positivism. Modern discoveries in genetics have, however, created a situation which seems to be leading toward a paradigm shift. The most significant of these discoveries are the findings of adaptive mutations, the phenomenon of transgenerational epigenetic inheritance, and, above all, the present deeply critical state of the concept of the gene.

The preventive effect of resiniferatoxin on the development of cold hypersensitivity induced by spinal nerve ligation: involvement of TRPM8.

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Koh, Won Uk; Choi, Seong-Soo; Kim, Ji Hyun; Yoon, Hye Joo; Ahn, Ho-Soo; Lee, Sun Kyung; Leem, Jeong Gil; Song, Jun Gol; Shin, Jin Woo

2016-06-21

Resiniferatoxin (RTX) is a potent analog of capsaicin and activates transient receptor potential (TRP) vanilloid type (TRPV) 1. In the current study, we investigated the preventive effect of perineural RTX on the development of cold hypersensitivity induced by spinal nerve ligation (SNL) in rats. Furthermore, we examined the association between the expression level of TRPV1, TRP ankyrin type (TRPA) 1 and TRP melastatin type (TRPM) 8 in the dorsal root ganglion (DRG) and cold hypersensitivity after SNL. RTX pretreatment prevented the development of SNL-induced hypersensitivity to mechanical, thermal, and cold stimuli. Western blot analysis 4 weeks after RTX pretreatment showed that RTX pretreatment decreased the protein expression level of SNL-induced TRPM8, but not TRPV1 or TRPA1, in the DRG of SNL rats. Immunofluorescent analysis revealed that up-regulated TRPM8-stained neurons after SNL co-localized with neurofilament 200-positive neurons located in the DRG. Pretreatment with perineural RTX significantly inhibits SNL-induced mechanical, thermal, and cold hypersensitivity. The antinociceptive effect of perineural RTX, especially on cold hypersensitivity, may be related to the suppression of TRPM8 expression in DRG.

Development and Application of a Test for Food-Induced Emotions.

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Geier, Uwe; Büssing, Arndt; Kruse, Pamela; Greiner, Ramona; Buchecker, Kirsten

2016-01-01

This study aimed to develop a test to measure food-induced emotions suitable for stable food and beverages. All of the experiments were conducted under the conditions of a consumer sensory evaluation according to German standard DIN 10974. Test development included descriptors' derivation and factor analysis as well as a comparison between the new test (empathic food test, EFT) and a hedonic sensory test and an unspecific psychological test, known as a multidimensional mood questionnaire (MDMQ). Nineteen sensory experts derived twelve items using free-choice profiling. After an exploratory factor analyses, ten of the intended twelve items were integrated into two scales. To compare the new questionnaire (EFT) to the MDMQ and a hedonic test, panels of 59 (EFT), 64 (MDMQ) and 63 (hedonic sensory test) untrained individuals described their perceptions after consuming sensorially similar pairs of milk, water, bread and sugar. The benchmark of comparison was the power to discriminate between the food pairs. Test-retest replicability was demonstrated. All three tests presented slight differences in sample preference and effect size depending on the offered products. These findings underscore the need to test new methods with a wide range of products. Further research is needed to investigate the relationship between sensorial perception and emotional response.

Development and Application of a Test for Food-Induced Emotions.

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Uwe Geier

Full Text Available This study aimed to develop a test to measure food-induced emotions suitable for stable food and beverages. All of the experiments were conducted under the conditions of a consumer sensory evaluation according to German standard DIN 10974. Test development included descriptors' derivation and factor analysis as well as a comparison between the new test (empathic food test, EFT and a hedonic sensory test and an unspecific psychological test, known as a multidimensional mood questionnaire (MDMQ. Nineteen sensory experts derived twelve items using free-choice profiling. After an exploratory factor analyses, ten of the intended twelve items were integrated into two scales. To compare the new questionnaire (EFT to the MDMQ and a hedonic test, panels of 59 (EFT, 64 (MDMQ and 63 (hedonic sensory test untrained individuals described their perceptions after consuming sensorially similar pairs of milk, water, bread and sugar. The benchmark of comparison was the power to discriminate between the food pairs. Test-retest replicability was demonstrated. All three tests presented slight differences in sample preference and effect size depending on the offered products. These findings underscore the need to test new methods with a wide range of products. Further research is needed to investigate the relationship between sensorial perception and emotional response.

DEVELOPMENT OF USER-FRIENDLY SIMULATION SYSTEM OF EARTHQUAKE INDUCED URBAN SPREADING FIRE

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