| 1. |
- Birney, Ewan, et al.
(author)
-
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
-
Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
|
|
| 2. |
- Bedford, Lynn, et al.
(author)
-
Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies
- 2008
-
In: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 28:33, s. 8189-98
-
Journal article (peer-reviewed)abstract
- Ubiquitin-positive intraneuronal inclusions are a consistent feature of the major human neurodegenerative diseases, suggesting that dysfunction of the ubiquitin proteasome system is central to disease etiology. Research using inhibitors of the 20S proteasome to model Parkinson's disease is controversial. We report for the first time that specifically 26S proteasomal dysfunction is sufficient to trigger neurodegenerative disease. Here, we describe novel conditional genetic mouse models using the Cre/loxP system to spatially restrict inactivation of Psmc1 (Rpt2/S4) to neurons of either the substantia nigra or forebrain (e.g., cortex, hippocampus, and striatum). PSMC1 is an essential subunit of the 26S proteasome and Psmc1 conditional knock-out mice display 26S proteasome depletion in targeted neurons, in which the 20S proteasome is not affected. Impairment of specifically ubiquitin-mediated protein degradation caused intraneuronal Lewy-like inclusions and extensive neurodegeneration in the nigrostriatal pathway and forebrain regions. Ubiquitin and alpha-synuclein neuropathology was evident, similar to human Lewy bodies, but interestingly, inclusion bodies contained mitochondria. We support this observation by demonstrating mitochondria in an early form of Lewy body (pale body) from Parkinson's disease patients. The results directly confirm that 26S dysfunction in neurons is involved in the pathology of neurodegenerative disease. The model demonstrates that 26S proteasomes are necessary for normal neuronal homeostasis and that 20S proteasome activity is insufficient for neuronal survival. Finally, we are providing the first reproducible genetic platform for identifying new therapeutic targets to slow or prevent neurodegeneration.
|
|
| 3. |
- Bourlat, Sarah, et al.
(author)
-
Deuterostome phylogeny reveals monophyletic chordates and the new phylum Xenoturbellida
- 2006
-
In: Nature. ; 444:7115, s. 85-88
-
Journal article (peer-reviewed)abstract
- Deuterostomes comprise vertebrates, the related invertebrate chordates (tunicates and cephalochordates) and three other inver- tebrate taxa: hemichordates, echinoderms and Xenoturbella1. The relationships between invertebrate and vertebrate deuterostomes are clearly important for understanding our own distant origins. Recent phylogenetic studies of chordate classes and a sea urchin have indicated that urochordates might be the closest inverte- brate sister group of vertebrates, rather than cephalochordates, as traditionally believed2–5. More remarkable is the suggestion that cephalochordates are closer to echinoderms than to vertebrates and urochordates, meaning that chordates are paraphyletic2. To study the relationships among all deuterostome groups, we have assembled an alignment of more than 35,000 homologous amino acids, including new data from a hemichordate, starfish and Xenoturbella. We have also sequenced the mitochondrial genome of Xenoturbella. We support the clades Olfactores (urochordates and vertebrates) and Ambulacraria (hemichordates and echino- derms6). Analyses using our new data, however, do not support a cephalochordate and echinoderm grouping and we conclude that chordates are monophyletic. Finally, nuclear and mitochondrial data place Xenoturbella as the sister group of the two ambulacrar- ian phyla1. As such, Xenoturbella is shown to be an independent phylum, Xenoturbellida, bringing the number of living deutero- stome phyla to four.
|
|
| 4. |
|
|
| 5. |
- Lowe, Robert, et al.
(author)
-
Predictive Regulation : Allostasis, Behavioural Flexibility and Fear Learning
- 2008
-
In: Proceedings of The Fourth Workshop on Anticipatory Behavior in Adaptive Learning Systems, Munich, June 26th, 2008. - : Istituto di Scienze e Tecnologie della Cognizione - CNR.
-
Conference paper (peer-reviewed)abstract
- Dynamical systems perspectives on emotion emphasize the importance of the regulatory interplay between brain, body and environment to adaptive behaviour. We suggest that a key facet of emotions, above all fear, consistent with this perspective lies in the allostatic regulation of constitutive/behavioural dynamics in terms of prediction and behavioural biases linking internal needs to external adaptive concerns. Allostatic emotional regulation in organizationally complex organisms permits enhanced adaptive behavioural flexibility relative to more reactive homeostatic dynamical systems. We discuss emotions as regulatory phenomena and provide a brief description of work in progress that will facilitate the gleaning of insights in this regard.
|
|
| 6. |
- Lowe, Robert, et al.
(author)
-
The degree of potential damage in agonistic contests and its effects on social aggression, territoriality and display evolution
- 2005
-
In: The 2005 IEEE Congress on Evolutionary Computation IEEE CEC 2005. - New York : IEEE conference proceedings. - 0780393635 ; , s. 351-358
-
Conference paper (peer-reviewed)abstract
- The potential for animals to inflict damage on one another whilst competing for indivisible resources is a factor of crucial importance when determining pay-offs to such animals and consequent likelihood of adopting an aggressive resource procurement strategy, a less costly display-based alternative or just a retreat response. Using computer simulations of evolving agents, we assessed the effects of degree of damage potential on social aggression and resource procuring strategies. Furthermore, we assessed the effects of evolving ritualized displays used in contests over resources relative to damage potential. Our results showed that aggressive interactions increased in frequency when the degree of damage potential was low. Ritualized displays tended to reduce aggressive approaches and mortality rate where damage potential was high and low but this was not the case at the intermediate level where aggression and mortality rate increased.
|
|
| 7. |
- Lowe, Robert, et al.
(author)
-
The dual-route hypothesis : evaluating a neurocomputational model of fear conditioning in rats
- 2009
-
In: Connection science (Print). - : Taylor & Francis. - 0954-0091 .- 1360-0494. ; 21:1, s. 15-37
-
Journal article (peer-reviewed)abstract
- Research on the neural bases of emotion raises much controversy and few quantitative models exist that can help address the issues raised. Here we replicate and dissect one of those models, Armony and colleagues’neurocomputational model of fear conditioning, which is based on LeDoux’s dual-route hypothesis regarding the rat fear circuitry. The importance of the model’s modular abstraction of the neuroanatomy, its use of population coding, and in particular the interplay between thalamo-amygdala and thalamo-cortical pathways are tested. We show that a trivially minimal version of the model can produce conditioning to a reinforced stimulus without recourse to the dual pathway structure, but a modification of the original model, which nevertheless preserves the thalamo-amygdala and (reduced) thalamo-cortical pathways, enables stronger conditioning to a conditioned stimulus. Implications for neurocomputational modelling approaches are discussed.
|
|
| 8. |
- Lowe, Robert, et al.
(author)
-
The Embodied Dynamics of Emotion, Appraisal and Attention
- 2007
-
In: Attention in Cognitive Systems. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783540773429 - 9783540773436 ; , s. 1-20
-
Conference paper (peer-reviewed)abstract
- Emotions can be considered inextricably linked to embodied appraisals - perceptions of bodily states that inform agents of how they are faring in the world relative to their own well-being. Emotion-appraisals are thus relational phenomena the relevance of which can be learned or evolutionarily selected for given a reliable coupling between agent-internal and environmental states. An emotion-appraisal attentional disposition permits agents to produce behaviour that exploits such couplings allowing for adaptive agent performance across agent-environment interactions. This chapter discusses emotions in terms of dynamical processes whereby attentional dispositions are considered central to an understanding of behaviour. The need to reconcile a dynamical systems perspective with an approach that views emotions as attentional dispositions representative of embodied relational phenomena (embodied appraisals) is argued for. Attention and emotion are considered to be features of adaptive agent behaviour that are interdependent in their temporal, structural and organizational relations.
|
|
| 9. |
|
|
| 10. |
- Montebelli, Alberto, et al.
(author)
-
Embodied anticipation for swift re-adaptation in neurocomputational cognitive architectures for robotic agents
- 2009
-
In: Proceedings of the 31th Annual Conference of the Cognitive Science Society. - Austin : Cognitive Science Society, Inc.. - 9780976831853 ; , s. 3082-3087
-
Conference paper (peer-reviewed)abstract
- The coupling between a body (in an extended sense that encompasses both neural and non-neural dynamics) and its environment is here conceived as a critical substrate for cognition. We propose and discuss the plan for a neurocomputational cognitive architecture for robotic agents, so far implemented in its minimalist form for supporting the behavior of a simple simulated agent. A non-neural internal bodily mechanism (crucially characterized by a time scale much slower than the normal sensory-motor interactions of the robot with its environment) extends the cognitive potential of a system composed of purely reactive parts with a dynamic action selection mechanism and the capacity to integrate information over time. The same non-neural mechanism is the foundation for a novel, minimalist anticipatory architecture, capable of swift re-adaptation to related yet novel tasks.
|
|
