The hypoxic environment imposes severe selective pressure on species living at high altitude. To understand the genetic bases of adaptation to high altitude in dogs, we performed whole-genome sequencing of 60 dogs including five breeds living at continuous altitudes along the Tibetan Plateau from 800 to 5100 m as well as one European breed. More than 150× sequencing coverage for each breed provides us with a comprehensive assessment of the genetic polymorphisms of the dogs, including Tibetan Mastiffs. Comparison of the breeds from different altitudes reveals strong signals of population differentiation at the locus of hypoxia-related genes including endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) and beta hemoglobin cluster. Notably, four novel nonsynonymous mutations specific to high-altitude dogs are identified at EPAS1, one of which occurred at a quite conserved site in the PAS domain. The association testing between EPAS1 genotypes and blood-related phenotypes on additional high-altitude dogs reveals that the homozygous mutation is associated with decreased blood flow resistance, which may help to improve hemorheologic fitness. Interestingly, EPAS1 was also identified as a selective target in Tibetan highlanders, though no amino acid changes were found. Thus, our results not only indicate parallel evolution of humans and dogs in adaptation to high-altitude hypoxia, but also provide a new opportunity to study the role of EPAS1 in the adaptive processes.
We developed a three-dimensional mini-type permanent magnetic resonance imaging (MRI) device in our lab. The purposes of this study were (1) for further development of MRI technologies, (2) for support of broadening practices of animal test modeling in medical research, and (3) for training more specialists from colleges or universities in the field of MRI. This paper describes the research and development at our lab(s), especially stressing on the design of the main magnet, the gradient coil and the radio frequency coil. In addition, the specific methodologies used in our lab(s) and the related data are emphasized. The 3D MRI technologies have met the needs of using small animals, super thin sections of live animal body and high imaging resolutions. MRI images of mice head and abdominal have been obtained successfully by using the imager that we developed. The imaging results and analyses have also been discussed.
We have previously reported that neuron and glia could collaboratively govern the immunomodulation in traumatic rats. Herein, we characterized the sequential involvement of cortical neuron, microglia, and astrocytes in the traumatic stress-mediated neuroimmune modulation. At day 1 of trauma, transient extracellular signal related kinase 1/2 (ERK1/2) activation was initiated in neuron and microglia, which was accompanied by RSK-1 expression in the cytosol. At day 3 of trauma, persistent ERK1/2 activation occurred in astrocytes, which were destined for the nucleus leading to Elk-1 expression. Furthermore, the functional overlap of ERK1/2 and neuroligin 1 in astrocytes was strengthened at day 3 of trauma and responsible for the recovery from the immnosuppression. These effects could be disrupted by ?-neurexin blockade. Altogether, we proposed the mechanism underlying the traumatic stress-induced immunosuppression, in which local activity ensured the initial establishment of neural circuitry in the frontal cortex. ERK1/2-signaling events are required for the temporal and spatial coordination between neuron and glial cells.
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