Dual DNA Methylation Patterns in the CNS Reveal Developmentally Poised Chromatin and Monoallelic Expression of Critical Genes

As a first step towards discovery of genes expressed from only one allele in the CNS, we used a tiling array assay for DNA sequences that are both methylated and unmethylated (the MAUD assay). We analyzed regulatory regions of the entire mouse brain transcriptome, and found that approximately 10% of the genes assayed showed dual DNA methylation patterns. They include a large subset of genes that display marks of both active and silent, i.e., poised, chromatin during development, consistent with a link between differential DNA methylation and lineage-specific differentiation within the CNS. Sixty-five of the MAUD hits and 57 other genes whose function is of relevance to CNS development and/or disorders were tested for allele-specific expression in F1 hybrid clonal neural stem cell (NSC) lines. Eight MAUD hits and one additional gene showed such expression. They include Lgi1, which causes a subtype of inherited epilepsy that displays autosomal dominance with incomplete penetrance; Gfra2, a receptor for glial cell line-derived neurotrophic factor GDNF that has been linked to kindling epilepsy; Unc5a, a netrin-1 receptor important in neurodevelopment; and Cspg4, a membrane chondroitin sulfate proteoglycan associated with malignant melanoma and astrocytoma in human. Three of the genes, Camk2a, Kcnc4, and Unc5a, show preferential expression of the same allele in all clonal NSC lines tested. The other six genes show a stochastic pattern of monoallelic expression in some NSC lines and bi-allelic expression in others. These results support the estimate that 1–2% of genes expressed in the CNS may be subject to allelic exclusion, and demonstrate that the group includes genes implicated in major disorders of the CNS as well as neurodevelopment

The importance of the altricial – precocial spectrum for social complexity in mammals and birds:A review

Various types of long-term stable relationships that individuals uphold, including cooperation and competition between group members, define social complexity in vertebrates. Numerous life history, physiological and cognitive traits have been shown to affect, or to be affected by, such social relationships. As such, differences in developmental modes, i.e. the ‘altricial-precocial’ spectrum, may play an important role in understanding the interspecific variation in occurrence of social interactions, but to what extent this is the case is unclear because the role of the developmental mode has not been studied directly in across-species studies of sociality. In other words, although there are studies on the effects of developmental mode on brain size, on the effects of brain size on cognition, and on the effects of cognition on social complexity, there are no studies directly investigating the link between developmental mode and social complexity. This is surprising because developmental differences play a significant role in the evolution of, for example, brain size, which is in turn considered an essential building block with respect to social complexity. Here, we compiled an overview of studies on various aspects of the complexity of social systems in altricial and precocial mammals and birds. Although systematic studies are scarce and do not allow for a quantitative comparison, we show that several forms of social relationships and cognitive abilities occur in species along the entire developmental spectrum. Based on the existing evidence it seems that differences in developmental modes play a minor role in whether or not individuals or species are able to meet the cognitive capabilities and requirements for maintaining complex social relationships. Given the scarcity of comparative studies and potential subtle differences, however, we suggest that future studies should consider developmental differences to determine whether our finding is general or whether some of the vast variation in social complexity across species can be explained by developmental mode. This would allow a more detailed assessment of the relative importance of developmental mode in the evolution of vertebrate social systems

Framework for integrating animal welfare into life cycle sustainability assessment

Purpose This study seeks to provide a framework for integrating animal welfare as a fourth pillar into a life cycle sustainability assessment and presents three alternative animal welfare indicators. Methods Animal welfare is assessed during farm life and during slaughter. The indicators differ in how they value premature death. All three consider (1) the life quality of an animal such as space allowance, (2) the slaughter age either as life duration or life fraction, and (3) the number of animals affected for providing a product unit, e.g. 1 Mcal. One of the indicators additionally takes into account a moral value denoting their intelligence and self-awareness. The framework allows for comparisons across studies and products and for applications at large spatial scales. To illustrate the framework, eight products were analysed and compared: beef, pork, poultry, milk, eggs, salmon, shrimps, and, as a novel protein source, insects. Results and discussion Insects are granted to live longer fractions of their normal life spans, and their life quality is less compromised due to a lower assumed sentience. Still, they perform worst according to all three indicators, as their small body sizes only yield low product quantities. Therefore, we discourage from eating insects. In contrast, milk is the product that reduces animal welfare the least according to two of the three indicators and it performs relatively better than other animal products in most categories. The difference in animal welfare is mostly larger for different animal products than for different production systems of the same product. This implies that, besides less consumption of animal-based products, a shift to other animal products can significantly improve animal welfare. Conclusions While the animal welfare assessment is simplified, it allows for a direct integration into life cycle sustainability assessment. There is a trade-off between applicability and indicator complexity, but even a simple estimate of animal welfare is much better than ignoring the issue, as is the common practice in life cycle sustainability assessments. Future research should be directed towards elaborating the life quality criterion and extending the product coverage.ISSN:0948-3349ISSN:1614-750

Spontaneous cortical activity is transiently poised close to criticality

Brain activity displays a large repertoire of dynamics across the sleep-wake cycle and even during anesthesia. It was suggested that criticality could serve as a unifying principle underlying the diversity of dynamics. This view has been supported by the observation of spontaneous bursts of cortical activity with scale-invariant sizes and durations, known as neuronal avalanches, in recordings of mesoscopic cortical signals. However, the existence of neuronal avalanches in spiking activity has been equivocal with studies reporting both its presence and absence. Here, we show that signs of criticality in spiking activity can change between synchronized and desynchronized cortical states. We analyzed the spontaneous activity in the primary visual cortex of the anesthetized cat and the awake monkey, and found that neuronal avalanches and thermodynamic indicators of criticality strongly depend on collective synchrony among neurons, LFP fluctuations, and behavioral state. We found that synchronized states are associated to criticality, large dynamical repertoire and prolonged epochs of eye closure, while desynchronized states are associated to sub-criticality, reduced dynamical repertoire, and eyes open conditions. Our results show that criticality in cortical dynamics is not stationary, but fluctuates during anesthesia and between different vigilance states.GH, CM and YF were supported by the CNRS, the Agence Nationale de la Recherche (ANR: V1-Complex) https://www.cnrs.fr. GH and GB were financed by the initial training network program FACETS-ITN (PITN-GA-2009- 237955) http://facets.kip.uni-heidelberg.de/ITN/. APA was supported by SEMAINE ERA-Net NEURON Project and by a Juan de la Cierva fellowship (IJCI-2014-21066) from the Spanish Ministry of Economy and Competitiveness. CM, GD and YF received funding from the EC grants BrainScales (FP7-2010- IST-FETPI 269921) and the flagship Human Brain Project (n.604102) https://www.humanbrainproject.eu/. The Utah array recordings were made possible through a loan by S.GruÈn (Research Center JuÈlich, INM6, Germany) and were part of a collaborative work with S. GruÈn and A. Riehle (INT, Marseille). AK received funding from the German Federal Ministry of Education and Research (BMBF 01GQ0420 to BCCN Freiburg and 01GQ0830 to BFNT Freiburg/TuÈbingen) https://www.bmbf.de/en/. GD is supported by the ERC Advanced Grant: DYSTRUCTURE (n. 295129), by the Spanish Research Project PSI2016-75688-P and by the the European Union's Horizon 2020 research and innovation programme under grant agreement n. 720270 (HBP SGA1). GD obtained support from the ERC Advanced Grant DYSTRUCTURE (n. 295129) gustavodecolab.com/dystructure/ and the Spanish Research Project PSI2013-42091- P. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript