@misc{15385,
  abstract     = {Relevant information about the data can be found in the 'Readme_Data.txt' file. 
A previous version of the publication can be found on BioRxiv: https://www.biorxiv.org/content/10.1101/2022.10.11.511691v4
and published in Plos Biology (2024)},
  author       = {Burnett, Laura and Koppensteiner, Peter and Symonova, Olga and Masson, Tomas and Vega Zuniga, Tomas A and Contreras, Ximena and Rülicke, Thomas and Shigemoto, Ryuichi and Novarino, Gaia and Jösch, Maximilian A},
  keywords     = {ASD, periaqueductal gray, perception, behavior, potassium channels},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice}},
  doi          = {10.15479/AT:ISTA:15385},
  year         = {2024},
}

@article{17142,
  abstract     = {Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in 3 independent mouse models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments—a nonperceptual trait. Focusing on a common cause of ASDs, the Setd5 gene mutation, we define the molecular mechanism. We show that the perceptual impairment is caused by a potassium channel (Kv1)-mediated hypoexcitability in a subcortical node essential for the initiation of escape responses, the dorsal periaqueductal grey (dPAG). Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance deficits, causally linking seemingly unrelated trait deficits to the dPAG. Furthermore, we show that different molecular mechanisms converge on similar behavioural phenotypes by demonstrating that the autism models Cul3 and Ptchd1, despite having similar behavioural phenotypes, differ in their functional and molecular alteration. Our findings reveal a link between rapid perception controlled by subcortical pathways and appropriate learned interactions with the environment and define a nondevelopmental source of such deficits in ASD.},
  author       = {Burnett, Laura and Koppensteiner, Peter and Symonova, Olga and Masson, Tomas and Vega Zuniga, Tomas A and Contreras, Ximena and Rülicke, Thomas and Shigemoto, Ryuichi and Novarino, Gaia and Jösch, Maximilian A},
  issn         = {1545-7885},
  journal      = {PLoS Biology},
  publisher    = {Public Library of Science},
  title        = {{Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice}},
  doi          = {10.1371/journal.pbio.3002668},
  volume       = {22},
  year         = {2024},
}

@article{15268,
  abstract     = {Apolipoprotein A‐I (apoA‐I) has a key function in the reverse cholesterol transport. However, aggregation of apoA‐I single point mutants can lead to hereditary amyloid pathology. Although several studies have tackled the biophysical and structural consequences introduced by these mutations, there is little information addressing the relationship between the evolutionary and structural features that contribute to the amyloid behavior of apoA‐I. We combined evolutionary studies, in silico mutagenesis and molecular dynamics (MD) simulations to provide a comprehensive analysis of the conservation and pathogenic role of the aggregation‐prone regions (APRs) present in apoA‐I. Sequence analysis demonstrated that among the four amyloidogenic regions described for human apoA‐I, only two (APR1 and APR4) are evolutionary conserved across different species of Sarcopterygii. Moreover, stability analysis carried out with the FoldX engine showed that APR1 contributes to the marginal stability of apoA‐I. Structural properties of full‐length apoA‐I models suggest that aggregation is avoided by placing APRs into highly packed and rigid portions of its native fold. Compared to silent variants extracted from the gnomAD database, the thermodynamic and pathogenic impact of amyloid mutations showed evidence of a higher destabilizing effect. MD simulations of the amyloid variant G26R evidenced the partial unfolding of the alpha‐helix bundle with the concomitant exposure of APR1 to the solvent, suggesting an insight into the early steps involved in its aggregation. Our findings highlight APR1 as a relevant component for apoA‐I structural integrity and emphasize a destabilizing effect of amyloid variants that leads to the exposure of this region.},
  author       = {Gisonno, Romina A. and Masson, Tomas and Ramella, Nahuel A. and Barrera, Exequiel E. and Romanowski, Víctor and Tricerri, M. Alejandra},
  issn         = {1097-0134},
  journal      = {Proteins: Structure, Function, and Bioinformatics},
  keywords     = {Molecular Biology, Biochemistry, Structural Biology},
  number       = {1},
  pages        = {258--269},
  publisher    = {Wiley},
  title        = {{Evolutionary and structural constraints influencing apolipoprotein A‐I amyloid behavior}},
  doi          = {10.1002/prot.26217},
  volume       = {90},
  year         = {2022},
}