[Effect of Sijunzi Decoction on intestinal barrier of type 2 diabetic mice].

This study aims to explore the improvement effect of Sijunzi Decoction on intestinal barrier in diabetic mice. A type 2 diabetes mellitus(T2DM) model was established in C57BL/6J mice by feeding them with high-sugar and high-fat diet combined with streptozotocin(STZ). The T2DM mice were randomly divided into a control group, a T2DM group, a donepezil(DON) group, a rosiglitazone(RGZ) group, and Sijunzi Decoction groups(7. 5, 15, and 30 g·kg~(-1)), and orally administered for six weeks. The body weight and fasting plasma glucose(FBG) of mice were recorded. Fasting plasma insulin(FINS) and insulin resistance index(HOMA-IR) were observed to assess insulin resistance(IR). Intestinal flora and levels of serotonin(5-HT), lipopolysaccharide(LPS), and short-chain fatty acids(SCFAs) in serum were analyzed. Changes in colonic structure and tight junction proteins occludin, claudin-1,and ZO-1 were observed through HE staining and immunohistochemistry. Spontaneous alternation test was conducted to observe the effect on spatial memory ability. Compared with the results in the control group, FBG and HOMA-IR in the T2DM group were significantly increased(P< 0. 01); species richness index(Sobs index), Shannon diversity index(Shannon index), and species abundance estimate index(Chao index) were decreased; LPS was significantly increased(P< 0. 001), while the levels of 5-HT,SCFAs, occludin, claudin-1, and ZO-1 were significantly decreased(P< 0. 01), indicating impaired colonic barrier function;spontaneous alternation accuracy was significantly decreased(P<0. 05). After 6 weeks of Sijunzi Decoction treatment, compared with the results in the T2DM group, FBG and HOMA-IR in the Sijunzi Decoction 15 g·kg~(-1) group were significantly decreased(P<0. 01);Sobs index, Shannon index, and Chao index were increased; LPS was significantly decreased(P<0. 01), while the levels of 5-HT,SCFAs, occludin, claudin-1, and ZO-1 were significantly increased(P< 0. 05), indicating improved colonic barrier function;spontaneous alternation accuracy was increased(P<0. 001). In conclusion, Sijunzi Decoction has the effect of improving intestinal barrier in diabetic mice.

Out of southern East Asia: the natural history of domestic dogs across the world.

The origin and evolution of the domestic dog remains a controversial question for the scientific community, with basic aspects such as the place and date of origin, and the number of times dogs were domesticated, open to dispute. Using whole genome sequences from a total of 58 canids (12 gray wolves, 27 primitive dogs from Asia and Africa, and a collection of 19 diverse breeds from across the world), we find that dogs from southern East Asia have significantly higher genetic diversity compared to other populations, and are the most basal group relating to gray wolves, indicating an ancient origin of domestic dogs in southern East Asia 33 000 years ago. Around 15 000 years ago, a subset of ancestral dogs started migrating to the Middle East, Africa and Europe, arriving in Europe at about 10 000 years ago. One of the out of Asia lineages also migrated back to the east, creating a series of admixed populations with the endemic Asian lineages in northern China before migrating to the New World. For the first time, our study unravels an extraordinary journey that the domestic dog has traveled on earth.

Genetic convergence in the adaptation of dogs and humans to the high-altitude environment of the tibetan plateau.

The high-altitude hypoxic environment represents one of the most extreme challenges for mammals. Previous studies of humans on the Tibetan plateau and in the Andes Mountains have identified statistical signatures of selection in different sets of loci. Here, we first measured the hemoglobin levels in village dogs from Tibet and those from Chinese lowlands. We found that the hemoglobin levels are very similar between the two groups, suggesting that Tibetan dogs might share similar adaptive strategies as the Tibetan people. Through a whole-genome sequencing approach, we have identified EPAS1 and HBB as candidate genes for the hypoxic adaptation on the Tibetan plateau. The population genetic analysis shows a significant convergence between humans and dogs in Tibet. The similarities in the sets of loci that exhibit putative signatures of selection and the hemoglobin levels between humans and dogs of the same environment, but not between human populations in different regions, suggests an extraordinary landscape of convergent evolution between human beings and their best friend on the Tibetan plateau.

The genomics of selection in dogs and the parallel evolution between dogs and humans.

The genetic bases of demographic changes and artificial selection underlying domestication are of great interest in evolutionary biology. Here we perform whole-genome sequencing of multiple grey wolves, Chinese indigenous dogs and dogs of diverse breeds. Demographic analysis show that the split between wolves and Chinese indigenous dogs occurred 32,000 years ago and that the subsequent bottlenecks were mild. Therefore, dogs may have been under human selection over a much longer time than previously concluded, based on molecular data, perhaps by initially scavenging with humans. Population genetic analysis identifies a list of genes under positive selection during domestication, which overlaps extensively with the corresponding list of positively selected genes in humans. Parallel evolution is most apparent in genes for digestion and metabolism, neurological process and cancer. Our study, for the first time, draws together humans and dogs in their recent genomic evolution.

Signature of balancing selection at the MC1R gene in Kunming dog populations.

Coat color in dog breeds is an excellent character for revealing the power of artificial selection, as it is extremely diverse and likely the result of recent domestication. Coat color is generated by melanocytes, which synthesize pheomelanin (a red or yellow pigment) or eumelanin (a black or brown pigment) through the pigment type-switching pathway, and is regulated by three genes in dogs: MC1R (melanocortin receptor 1), CBD103 (ß-defensin 103), and ASIP (agouti-signaling protein precursor). The genotypes of these three gene loci in dog breeds are associated with coat color pattern. Here, we resequenced these three gene loci in two Kunming dog populations and analyzed these sequences using population genetic approaches to identify evolutionary patterns that have occurred at these loci during the recent domestication and breeding of the Kunming dog. The analysis showed that MC1R undergoes balancing selection in both Kunming dog populations, and that the Fst value for MC1R indicates significant genetic differentiation across the two populations. In contrast, similar results were not observed for CBD103 or ASIP. These results suggest that high heterozygosity and allelic differences at the MC1R locus may explain both the mixed color coat, of yellow and black, and the difference in coat colors in both Kunming dog populations.