5 research outputs found
Limited emission dredging: Design of a decision-making tool aimed at the technically, economically and socially feasible reduction of dredging fleet emission
Technology, Policy and Managemen
Transcription-associated DNA DSBs activate p53 during hiPSC-based neurogenesis
Funding Information: We thank the Stem Cell Core, Genome Analysis and Technology Core, and the Flow Cytometry Core at the University of Virginia School of Medicine. This work was supported by a Wagner Fellowship (N.M, H.M.R), F31AG062042 (N.M), 5T32GM008136 (N.M, H.M.R), 5T32GM007267 (N.M), a Maddy Deal Pilot Grant (M.J.M), the Owens (M.J.M.) and Familant (M.J.M.) Family Funds, McDonnell Foundation (I.E.B), FONDECYT Regular #1191737 from the Agencia Nacional de Investigación y Desarrollo de Chile (I.E.B.) and R01GM101192 (Y.H.W). Funding Information: We thank the Stem Cell Core, Genome Analysis and Technology Core, and the Flow Cytometry Core at the University of Virginia School of Medicine. This work was supported by a Wagner Fellowship (N.M, H.M.R), F31AG062042 (N.M), 5T32GM008136 (N.M, H.M.R), 5T32GM007267 (N.M), a Maddy Deal Pilot Grant (M.J.M), the Owens (M.J.M.) and Familant (M.J.M.) Family Funds, McDonnell Foundation (I.E.B), FONDECYT Regular #1191737 from the Agencia Nacional de Investigación y Desarrollo de Chile (I.E.B.) and R01GM101192 (Y.H.W). Publisher Copyright: © 2022, The Author(s).Neurons are overproduced during cerebral cortical development. Neural progenitor cells (NPCs) divide rapidly and incur frequent DNA double-strand breaks (DSBs) throughout cortical neurogenesis. Although half of the neurons born during neurodevelopment die, many neurons with inaccurate DNA repair survive leading to brain somatic mosaicism. Recurrent DNA DSBs during neurodevelopment are associated with both gene expression level and gene length. We used imaging flow cytometry and a genome-wide DNA DSB capture approach to quantify and map DNA DSBs during human induced pluripotent stem cell (hiPSC)-based neurogenesis. Reduced p53 signaling was brought about by knockdown (p53KD); p53KD led to elevated DNA DSB burden in neurons that was associated with gene expression level but not gene length in neural progenitor cells (NPCs). Furthermore, DNA DSBs incurred from transcriptional, but not replicative, stress lead to p53 activation in neurotypical NPCs. In p53KD NPCs, DNA DSBs accumulate at transcription start sites of genes that are associated with neurological and psychiatric disorders. These findings add to a growing understanding of how neuronal genome dynamics are engaged by high transcriptional or replicative burden during neurodevelopment
Making amphibian conservation more effective
Amphibians face an extinction crisis. Hundreds of species may be lost as conservation scientists and practitioners struggle to identify remedies to poorly understood declines spanning several decades. Due to various life history characteristics and a range of drivers, amphibians continue to be especially hard-hit, more so than any other vertebrate group. In this special issue of Conservation Evidence, studies that report the effectiveness of amphibian conservation interventions are presented to add to the rapidly growing body of literature on this topic. We here summarise the current understanding of global amphibian declines to highlight the importance of applying evidence-based strategies to amphibian conservation
Commercial farming threatens Chinese Giant Salamander conservation through disease, introgression and overexploitation.
The Chinese giant salamander (Andrias davidianus; CGS), endemic to China and Critically Endangered, has been identified as the amphibian species most in need of conservation action1. Since 2004, a rapidly growing industry to farm CGS for food, subsidised in order to diversify and bolster the rural economy and employment opportunities, has developed throughout much of China, centred on Shaanxi Province.
By mid-2012 at least 141 CGS farms had been licensed in the province, with many more farms unrecorded. In 2011, 2.6 million farmed CGS were documented in Shaanxi Province alone. Wild-caught CGS continue to be in demand for breeding farms even though their capture is illegal. This is partly due to problems in getting > F1 animals to breed and partly due to huge (up to 100%) losses of farm stock from disease epidemics and the consequent requirement to restock affected farms2. This demand for breeding stock, which can command very high prices, has driven recent overexploitation and near-depletion from the wild.
We visited CGS farms during outbreaks of fatal disease and, using PCR, we identified Ranavirus infection as the cause2. Thirty-nine of 43 additional farms surveyed reported that they had suffered disease outbreaks consistent with ranaviral disease. Three of the four farms that did not report disease held stock of ≤ 3,000 animals, lower than the mean number of 8,354 CGS per surveyed farm. The industrial-scale farming, high stocking densities, and trade in animals across China in the absence of biosecurity measures has led to a system that has fostered the propagation and spread of infectious disease.
Genetic screening of wild and farmed CGS has identified geographic structuring of wild salamanders but genetic mixing and hybridisation of farmed animals3. The current structure and management of the CGS farming industry presents conservation threats to extant wild CGS (and possibly other wild fauna) through the discharge of contaminated farm wastewater or the escape of infected individuals to the wild. Additional disease and genetic threats to CGS conservation are posed by the Chinese government-sponsored conservation action of purchasing farmed animals for release into the wild without adherence to IUCN guidelines, such as pathogen or genetic screening, identification of suitable habitat or post-release monitoring.
Complete separation of farmed and wild CGS populations and improved CGS farm management, including the quarantining of new stock and the disinfection of waste-water, is recommended in order to reduce disease risks to both farmed and wild animals. The number and native locations of CGS evolutionary significant units should be identified and in situ protection measures put in place and enforced. A CGS conservation action plan should be developed and, if conservation breeding and release is an identified requirement, this should be conducted separately from commercial farming and should follow IUCN guidelines.
References
1. Isaac, N.J.B., Redding, D.W., Meredith, H.M.R. & Safi, K. (2012) Phylogenetically-informed priorities for amphibian conservation. PLoS ONE 7, e43912.
2. Cunningham, A. A., Turvey, S. T., Zhou, F., Meredith, H., Guan, W., Liu, X., Sun, C., Wang, Z. & Wu, M. (2016) The development of the Chinese giant salamander (Andrias davidianus) farming industry in Shaanxi Province, China: conservation threats and opportunities. Oryx 50, 265-273.
3. Yan, F., Lü, J., Zhang, B., Yuan, Z., Huang, S., Wei, G., Mi, X., Zou, D., Chen, S., Wu, M., Xiao, H., Liang, Z., Tapley, B., Papenfuss, T. J., Cunningham, A. A., Murphy, R. W., Zhang, Y. & Che, J. The Chinese giant salamander exemplifies the hidden extinction of cryptic species. Submitted.peerReviewedunknown accessibilityei tietoa saavutettavuudest
A behavioural and electrophysiological study of factors involved in the relationship between stress and alcohol dependence
Alcohol dependence causes disruption to both work and family life and the associated costs are £150+ million in the UK alone. Stressful life events play a role in initiation of uncontrolled (dependent) drinking and can precipitate relapse to high ethanol consumption after treatment / abstinence. The primary neurological substrate for ethanol reward is the mesolimbic dopamine system of the medial forebrain bundle. Activation of the hypothalamopituitaryadrenal axis (the hormonal response to many stresssors) plays a role in the control of ethanol consumption and relapse, and modulation of neuronal activity by chronic calcium channel blockade decreases ethanol intake, tolerance and withdrawal. The stress system and calcium channel blockade both affect the dopaminergic reward pathways. Hypothesis: Stress and the stress hormone, corticosterone, play a crucial role in the modulation of ethanol consumption and the long term changes resulting from chronic ethanol intake. This hypothesis was tested by investigating the effects of:• social status and calcium channel blockade on chronic ethanol intake (free choice 5, 10, 20% ethanol and water) of group housed rats.• social stress from defeat by an aggressive resident on ethanol preference of low ethanol preference C57 mice.• 6 days abstinence from chronic ethanol intake (liquid diet) on NMDA-stimulated firing of dopaminergic, ventral tegmental area, cells and the role of corticosterone in modulation of this response to NMDA. The main findings from these studies indicate that, while the social stress of group housing under laboratory conditions may be insufficient to elevate ethanol intake, repeated defeat significantly increases ethanol intake. However, neither chronic ethanol consumption nor corticosterone seemd to have any effect on NMDA-stimulated dopamine cell firing. These results indicate a significant role for social stress in the modulation of ethanol intake but possibly not via the action of corticosterone on NMDA-stimulation of the mesolimbic dopamine system
