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- 2019
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Tidskriftsartikel (refereegranskat)
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- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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- O'Connor, M. I., et al.
(författare)
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A general biodiversity-function relationship is mediated by trophic level
- 2017
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Ingår i: Oikos. - : Wiley. - 0030-1299. ; 126:1, s. 18-31
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Tidskriftsartikel (refereegranskat)abstract
- Species diversity affects the functioning of ecosystems, including the efficiency by which communities capture limited resources, produce biomass, recycle and retain biologically essential nutrients. These ecological functions ultimately support the ecosystem services upon which humanity depends. Despite hundreds of experimental tests of the effect of biodiversity on ecosystem function (BEF), it remains unclear whether diversity effects are sufficiently general that we can use a single relationship to quantitatively predict how changes in species richness alter an ecosystem function across trophic levels, ecosystems and ecological conditions. Our objective here is to determine whether a general relationship exists between biodiversity and standing biomass. We used hierarchical mixed effects models, based on a power function between species richness and biomass production (Y = a x S-b), and a database of 374 published experiments to estimate the BEF relationship (the change in biomass with the addition of species), and its associated uncertainty, in the context of environmental factors. We found that the mean relationship (b = 0.26, 95% CI: 0.16, 0.37) characterized the vast majority of observations, was robust to differences in experimental design, and was independent of the range of species richness levels considered. However, the richness-biomass relationship varied by trophic level and among ecosystems; in aquatic systems b was nearly twice as large for consumers (herbivores and detritivores) compared to primary producers; in terrestrial ecosystems, b for detritivores was negative but depended on few studies. We estimated changes in biomass expected for a range of changes in species richness, highlighting that species loss has greater implications than species gains, skewing a distribution of biomass change relative to observed species richness change. When biomass provides a good proxy for processes that underpin ecosystem services, this relationship could be used as a step in modeling the production of ecosystem services and their dependence on biodiversity.
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- Schwandt, Melanie L., et al.
(författare)
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Gene-Environment Interactions and Response to Social Intrusion in Male and Female Rhesus Macaques
- 2010
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 67:4, s. 323-330
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic factors interact with environmental stressors to moderate risk for human psychopathology, but sex may also be an important mediating factor. Different strategies for coping with environmental stressors have evolved in males and females, and these differences may underlie the differential prevalence of certain types of psychopathology in the two sexes. In this study, we investigated the possibility of sex-specific gene-environment interactions in a nonhuman primate model of response to social threat. Methods: Rhesus macaques (77 males and 106 females) were exposed to an unfamiliar conspecific. Using factor analysis, we identified three behavioral factors characterizing the response to social threat. Monkeys were genotyped for the serotonin transporter-linked polymorphism (5-HTTLPR), and the effects of genotype, early life stress, and sex on behavioral responses were evaluated. Results: Factor analysis produced five factors: High-Risk Aggression, Impulsivity/Novelty-Seeking, Gregariousness/Boldness, Harm Avoidance, and Redirected Aggression. Overall, males displayed higher levels of High-Risk Aggression and Gregariousness/Boldness than females. Levels of High-Risk Aggression in males carrying the s allele were significantly higher if they were also exposed to early adversity in the form of peer rearing. Conclusions: Our findings support those from studies in humans suggesting that males are more vulnerable to externalizing or aggression-related disorders. The results highlight the importance of interactions that exist among behavior, genes, and the environment and suggest that sex differences in vulnerability to psychopathology may be grounded in our evolutionary history.
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- Smerdon, J. E., et al.
(författare)
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Comparing proxy and model estimates of hydroclimate variability and change over the Common Era
- 2017
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 13:12, s. 1851-1900
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Tidskriftsartikel (refereegranskat)abstract
- Water availability is fundamental to societies and ecosystems, but our understanding of variations in hydroclimate (including extreme events, flooding, and decadal periods of drought) is limited because of a paucity of modern instrumental observations that are distributed unevenly across the globe and only span parts of the 20th and 21st centuries. Such data coverage is insufficient for characterizing hydroclimate and its associated dynamics because of its multidecadal to centennial variability and highly regionalized spatial signature. High-resolution (seasonal to decadal) hydroclimatic proxies that span all or parts of the Common Era (CE) and paleoclimate simulations from climate models are therefore important tools for augmenting our understanding of hydroclimate variability. In particular, the comparison of the two sources of information is critical for addressing the uncertainties and limitations of both while enriching each of their interpretations. We review the principal proxy data available for hydroclimatic reconstructions over the CE and highlight the contemporary understanding of how these proxies are interpreted as hydroclimate indicators. We also review the available last-millennium simulations from fully coupled climate models and discuss several outstanding challenges associated with simulating hydroclimate variability and change over the CE. A specific review of simulated hydroclimatic changes forced by volcanic events is provided, as is a discussion of expected improvements in estimated radiative forcings, models, and their implementation in the future. Our review of hydroclimatic proxies and last-millennium model simulations is used as the basis for articulating a variety of considerations and best practices for how to perform proxy-model comparisons of CE hydroclimate. This discussion provides a framework for how best to evaluate hydroclimate variability and its associated dynamics using these comparisons and how they can better inform interpretations of both proxy data and model simulations. We subsequently explore means of using proxy-model comparisons to better constrain and characterize future hydroclimate risks. This is explored specifically in the context of several examples that demonstrate how proxy-model comparisons can be used to quantitatively constrain future hydroclimatic risks as estimated from climate model projections.
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- Bodin, Örjan, et al.
(författare)
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Improving network approaches to the study of complex social–ecological interdependencies
- 2019
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 2:7, s. 551-559
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Tidskriftsartikel (refereegranskat)abstract
- Achieving effective, sustainable environmental governance requires a better understanding of the causes and consequences of the complex patterns of interdependencies connecting people and ecosystems within and across scales. Network approaches for conceptualizing and analysing these interdependencies offer one promising solution. Here, we present two advances we argue are needed to further this area of research: (i) a typology of causal assumptions explicating the causal aims of any given network-centric study of social–ecological interdependencies; (ii) unifying research design considerations that facilitate conceptualizing exactly what is interdependent, through what types of relationships and in relation to what kinds of environmental problems. The latter builds on the appreciation that many environmental problems draw from a set of core challenges that re-occur across contexts. We demonstrate how these advances combine into a comparative heuristic that facilitates leveraging case-specific findings of social–ecological interdependencies to generalizable, yet context-sensitive, theories based on explicit assumptions of causal relationships.
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- Baker, Maggie, et al.
(författare)
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Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 114:44, s. 11769-11774
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Tidskriftsartikel (refereegranskat)abstract
- Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male, n = 13). Focusing on genes with roles in stress response and behavior, we assessed the effects of rearing on H3K4me3 binding by ANOVA. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene OXTR, for which we observed a corresponding decrease in RNA expression. Based on this finding, we performed behavioral analyses to deter mine whether a gain-of-function nonsynonymous OXTR SNP inter acted with early stress to influence relevant behavioral stress reactivity phenotypes (n = 194), revealing that this SNP partially rescued the PR phenotype. PR infants exhibited higher levels of separation anxiety and arousal in response to social separation, but infants carrying the alternative OXTR allele did not exhibit as great a separation response. These data indicate that the oxytocin system is involved in social-separation response and suggest that epigenetic down-modulation of OXTR could contribute to behavior al differences observed in PR animals. Epigenetic changes at OXTR may represent predictive adaptive responses that could impart readiness to respond to environmental challenge or maintain proximity to a caregiver but also contribute to behavioral pathology. Our data also demonstrate that OXTR polymorphism can permit animals to partially overcome the detrimental effects of early maternal deprivation, which could have translational implications for human psychiatric disorders.
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