Neuropeptide S (NPS) and its receptor (NPSR) constitute a novel neuropeptide system that is involved in regulating arousal and anxiety. The NPS precursor mRNA is highly expressed in a previously undescribed group of neurons located between the locus coeruleus (LC) and Barrington's nucleus. We report here that the majority of NPS-expressing neurons in the LC area and the principal sensory trigeminal nucleus are glutamatergic neurons, whereas many NPS-positive neurons in the lateral parabrachial nucleus coexpress corticotropin-releasing factor (CRF). In addition, we describe a comprehensive map of NPSR mRNA expression in the rat brain. High levels of expression are found in areas involved in olfactory processing, including the anterior olfactory nucleus, the endopiriform nucleus, and the piriform cortex. NPSR mRNA is expressed in several regions mediating anxiety responses, including the amygdaloid complex and the paraventricular hypothalamic nucleus. NPSR mRNA is also found in multiple key regions of sleep neurocircuitries, such as the thalamus, the hypothalamus, and the preoptic region. In addition, NPSR mRNA is strongly expressed in major output and input regions of hippocampus, including the parahippocampal regions, the lateral entorhinal cortex, and the retrosplenial agranular cortex. Multiple hypothalamic nuclei, including the dorsomedial and the ventromedial hypothalamic nucleus and the posterior arcuate nucleus, express high levels of NPSR mRNA, indicating that NPS may regulate energy homeostasis. These data suggest that the NPS system may play a key role in modulating a variety of physiological functions, especially arousal, anxiety, learning and memory, and energy balance.

Comparative population genomics offers an opportunity to discover the signatures of artificial selection during animal domestication, however, their function cannot be directly revealed. We discover the selection signatures using genome-wide comparisons among 40 mallards, 36 indigenous-breed ducks, and 30 Pekin ducks. Then, the phenotypes are fine-mapped based on resequencing of 1026 ducks from an F2 segregating population generated by wild × domestic crosses. Interestingly, the two key economic traits of Pekin duck are associated with two selective sweeps with fixed mutations. A novel intronic insertion most possibly leads to a splicing change in MITF accounted for white duck down feathers. And a putative long-distance regulatory mutation causes continuous expression of the IGF2BP1 gene after birth which increases body size by 15% and feed efficiency by 6%. This study provides new insights into genotype–phenotype associations in animal research and constitutes a promising resource on economically important genes in fowl.

We have recently shown that Neuropeptide S (NPS) can promote arousal and induce anxiolytic-like effects after central administration in rodents. Another study reported a number of natural polymorphisms in the human NPS receptor gene. Some of these polymorphisms were associated with increased risk of asthma and possibly other forms of atopic diseases, but the physiological consequences of the mutations remain unclear. One of the polymorphisms produces an Asn-Ile exchange in the first extracellular loop of the receptor protein, and a C-terminal splice variant of the NPS receptor was found overexpressed in human asthmatic airway tissue. We sought to study the pharmacology of the human receptor variants in comparison with the murine receptor protein. Here, we report that the N107I polymorphism in the human NPS receptor results in a gain-offunction characterized by an increase in agonist potency without changing binding affinity in NPSR Ile 107 . In contrast, the C-terminal splice variant of the human NPS receptor shows a pharmacological profile similar to NPSR Asn 107 . The mouse NPS receptor, which also carries an Ile residue at position 107, displays an intermediate pharmacological profile. Structureactivity relationship studies show that the amino terminus of NPS is critical for receptor activation. The altered pharmacology of the Ile 107 isoform of the human NPS receptor implies a mechanism of enhanced NPS signaling that might have physiological significance for brain function as well as peripheral tissues that express NPS receptors.Neuropeptide S (NPS) is the endogenous ligand of an orphan G protein-coupled receptor (GPCR). The NPS receptor (NPSR) belongs to the subfamily of peptide GPCRs and is widely expressed in the brain, with highest levels found in hypothalamus, amygdala, endopiriform nucleus, cortex, subiculum, and nuclei of the thalamic midline. In contrast, the NPS precursor mRNA is found in only a few brain structures (Xu et al., 2004). Highest levels of NPS precursor expression were detected in a novel nucleus located in between the noradrenergic locus coeruleus and Barrington's nucleus in the pontine area of the rat brain stem. Other brain regions of high NPS precursor expression include the lateral parabrachial nucleus, sensory principle 5 nucleus, and a few scattered neurons in the amygdala and dorsomedial hypothalamic nucleus. In addition, we found high expression of NPS and NPSR mRNA in endocrine tissues, including thyroid, mammary, and salivary glands, but did not observe significant levels in rat lung tissue.Central administration of NPS promotes behavioral arousal and suppresses all stages of sleep in rodents. Furthermore, NPS was found to produce anxiolytic-like effects in a battery of four different tests that measure behavioral responses of rodents to novelty or stress. NPS was shown to induce transient increases of intracellular Ca 2ϩ , indicating that it might have excitatory effects at the cellular level (Xu et al., 2004).Recently, a number of polymorphisms in the human NPS rece...

Understanding the genetic changes underlying phenotypic variation in sheep (Ovis aries) may facilitate our efforts towards further improvement. Here, we report the deep resequencing of 248 sheep including the wild ancestor (O. orientalis), landraces, and improved breeds. We explored the sheep variome and selection signatures. We detected genomic regions harboring genes associated with distinct morphological and agronomic traits, which may be past and potential future targets of domestication, breeding, and selection. Furthermore, we found non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds. We identified PDGFD as a likely causal gene for fat deposition in the tails of sheep through transcriptome, RT-PCR, qPCR, and Western blot analyses. Our results provide insights into the demographic history of sheep and a valuable genomic resource for future genetic studies and improved genome-assisted breeding of sheep and other domestic animals.