␣-Synuclein is a highly conserved presynaptic protein of unknown function. A mutation in the protein has been causally linked to Parkinson's disease in humans, and the normal protein is an abundant component of the intraneuronal inclusions (Lewy bodies) characteristic of the disease. ␣-Synuclein is also the precursor to an intrinsic component of extracellular plaques in Alzheimer's disease. The ␣-synuclein sequence is largely composed of degenerate 11-residue repeats reminiscent of the amphipathic ␣-helical domains of the exchangeable apolipoproteins. We hypothesized that ␣-synuclein should associate with phospholipid bilayers and that this lipid association should stabilize an ␣-helical secondary structure in the protein. We report that ␣-synuclein binds to small unilamellar phospholipid vesicles containing acidic phospholipids, but not to vesicles with a net neutral charge. We further show that the protein associates preferentially with vesicles of smaller diameter (20 -25 nm) as opposed to larger (ϳ125 nm) vesicles. Lipid binding is accompanied by an increase in ␣-helicity from 3% to approximately 80%. These observations are consistent with a role in vesicle function at the presynaptic terminal.
The most commonly cited descriptions of the behavioral characteristics of habituation come from two papers published almost 40 years ago (Thompson and Spencer, 1966;Groves and Thompson, 1970). In August 2007, the authors of this review, who study habituation in a wide range of species and paradigms, met to discuss their work on habituation and to revisit and refine the characteristics of habituation. This review offers a re-evaluation of the characteristics of habituation in light of these discussions. We made substantial changes to only a few of the characteristics, usually to add new information and expand upon the description rather than to substantially alter the original point.In the 20 th century, great progress was made in understanding the behavioral characteristics of habituation. A landmark paper published by Thompson and Spencer in 1966 clarified the definition of habituation, synthesized the research to date and presented a list of nine behavioral characteristics of habituation that appeared to be common in all organisms studied The history of habituation and the historical context of Thompson & Spencer's (1966) distillation are reviewed more fully in an article by Thompson (2009) that is included in this issue. This list was repeated and expanded upon by Groves and Thompson in 1970. These two papers are now citation classics and are considered to be the authorities on the characteristics of habituation. In August 2007, a group of 15 researchers (the authors of this review) who study habituation in a wide range of species and paradigms met to revisit these characteristics and refine them based on the 40 years of research since Thompson and Spencer 1966. The descriptions and characteristics from 1966 have held up remarkably well, and the revisions we have made to them were often for clarity rather than content. We made substantial changes to only a few of the characteristics, usually to add new information and expand upon the description rather than to substantially alter the original point. We restricted ourselves to an analysis of habituation; there was insufficient time for detailed discussions of the other form of non-associative learning "sensitization." Thus this review is restricted to our discussions of habituation and dishabituation (as it relates directly to habituation).Many people will be surprised to learn that, although habituation is termed "the simplest form of learning" and is well studied behaviorally, remarkably little is known about the neural mechanisms underlying habituation. Researchers who work on this form of learning believe that because habituation allows animals to filter out irrelevant stimuli and focus selectively on
The zebra finch is an important model organism in several fields1,2 with unique relevance to human neuroscience3,4. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken5—the only bird with a sequenced genome until now6. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes7. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour.
A male zebra finch learns a song by listening to a tutor, but song learning is normally restricted to a critical period in juvenile development. Here we identify an RNA whose expression in the song control circuit is altered during this critical period. The RNA encodes a soluble presynaptic protein that forms a predicted amphipathic alpha helix typical of the lipid-binding domain in apolipoproteins. We show this protein, which we call synelfin, to be the homolog of the human non-A beta component (and its precursor) recently purified from Alzheimer's disease amyloid. We suggest this highly conserved protein may serve a novel function critical to the regulation of vertebrate neural plasticity.
High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1–4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.
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