Impacts of Population Size and Domestication Process on Genetic Diversity and Genetic Load in Genus Ovis.

In theoretical biology, a prevailing hypothesis posits a profound interconnection between effective population size (Ne), genetic diversity, inbreeding, and genetic load. The domestication and improvement processes are believed to be pivotal in diminishing genetic diversity while elevating levels of inbreeding and increasing genetic load. In this study, we performed a whole genome analysis to quantity genetic diversity, inbreeding, and genetic load across seven wild Ovis species and five domesticated sheep breeds. Our research demonstrates that the genetic load and diversity of species in the genus Ovis have no discernible impact on recent Ne, and three species within the subgenus Pachyceros tend to carry a higher genetic load and lower genetic diversity patterns. The results coincide with these species' dramatic decline in population sizes within the subgenus Pachyceros ~80-250 thousand years ago. European mouflon presented with the lowest Ne, lower genetic diversity, and higher individual inbreeding coefficient but a lower genetic load (missense and LoF). This suggests that the small Ne of European mouflon could reduce harmful mutations compared to other species within the genus Ovis. We showed lower genetic diversity in domesticated sheep than in Asiatic mouflon, but counterintuitive patterns of genetic load, i.e., lower weak genetic load (missense mutation) and no significant difference in strong genetic load (LoF mutation) between domestic sheep and Asiatic mouflon. These findings reveal that the "cost of domestication" during domestication and improvement processes reduced genetic diversity and purified weak genetic load more efficiently than wild species.

Single-cell transcriptome and metagenome profiling reveals the genetic basis of rumen functions and convergent developmental patterns in ruminants.

The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.

Genomic Landscape of Copy Number Variations and Their Associations with Climatic Variables in the World's Sheep.

Sheep show characteristics of phenotypic diversity and adaptation to diverse climatic regions. Previous studies indicated associations between copy number variations (CNVs) and climate-driven adaptive evolution in humans and other domestic animals. Here, we constructed a genomic landscape of CNVs (n = 39,145) in 47 old autochthonous populations genotyped at a set of high-density (600 K) SNPs to detect environment-driven signatures of CNVs using a multivariate regression model. We found 136 deletions and 52 duplications that were significantly (Padj. < 0.05) associated with climatic variables. These climate-mediated selective CNVs are involved in functional candidate genes for heat stress and cold climate adaptation (e.g., B3GNTL1, UBE2L3, and TRAF2), coat and wool-related traits (e.g., TMEM9, STRA6, RASGRP2, and PLA2G3), repairing damaged DNA (e.g., HTT), GTPase activity (e.g., COPG), fast metabolism (e.g., LMF2 and LPIN3), fertility and reproduction (e.g., SLC19A1 and CCDC155), growth-related traits (e.g., ADRM1 and IGFALS), and immune response (e.g., BEGAIN and RNF121) in sheep. In particular, we identified significant (Padj. < 0.05) associations between probes in deleted/duplicated CNVs and solar radiation. Enrichment analysis of the gene sets among all the CNVs revealed significant (Padj. < 0.05) enriched gene ontology terms and pathways related to functions such as nucleotide, protein complex, and GTPase activity. Additionally, we observed overlapping between the CNVs and 140 known sheep QTLs. Our findings imply that CNVs can serve as genomic markers for the selection of sheep adapted to specific climatic conditions.

Whole-genome selective scans detect genes associated with important phenotypic traits in goat (Capra hircus).

Goats with diverse economic phenotypic traits play an important role in animal husbandry. However, the genetic mechanisms underlying complex phenotypic traits are unclear in goats. Genomic studies of variations provided a lens to identify functional genes. In this study, we focused on the worldwide goat breeds with outstanding traits and used whole-genome resequencing data in 361 samples from 68 breeds to detect genomic selection sweep regions. We identified 210-531 genomic regions with six phenotypic traits, respectively. Further gene annotation analysis revealed 332, 203, 164, 300, 205, and 145 candidate genes corresponding with dairy, wool, high prolificacy, poll, big ear, and white coat color traits. Some of these genes have been reported previously (e.g., KIT, KITLG, NBEA, RELL1, AHCY, and EDNRA), while we also discovered novel genes, such as STIM1, NRXN1, LEP, that may be associated with agronomic traits like poll and big ear morphology. Our study found a set of new genetic markers for genetic improvement in goats and provided novel insights into the genetic mechanisms of complex traits.

Whole-body adipose tissue multi-omic analyses in sheep reveal molecular mechanisms underlying local adaptation to extreme environments.

The fat tail of sheep is an important organ that has evolved to adapt to extreme environments. However, the genetic mechanisms underlying the fat tail phenotype remain poorly understood. Here, we characterize transcriptome and lipidome profiles and morphological changes in 250 adipose tissues from two thin-tailed and three fat-tailed sheep populations in summer and winter. We implement whole-genome selective sweep tests to identify genetic variants related to fat-tails. We identify a set of functional genes that show differential expression in the tail fat of fat-tailed and thin-tailed sheep in summer and winter. These genes are significantly enriched in pathways, such as lipid metabolism, extracellular matrix (ECM) remodeling, molecular transport, and inflammatory response. In contrast to thin-tailed sheep, tail fat from fat-tailed sheep show slighter changes in adipocyte size, ECM remodeling, and lipid metabolism, and had less inflammation in response to seasonal changes, indicating improved homeostasis. Whole-genome selective sweep tests identify genes involved in preadipocyte commitment (e.g., BMP2, PDGFD) and terminal adipogenic differentiation (e.g., VEGFA), which could contribute to enhanced adipocyte hyperplasia. Altogether, we establish a model of regulatory networks regulating adipose homeostasis in sheep tails. These findings improve our understanding of how adipose homeostasis is maintained, in response to extreme environments in animals.

Integrated analysis of the whole transcriptome of skeletal muscle reveals the ceRNA regulatory network related to the formation of muscle fibers in Tan sheep.

Meat quality is highly influenced by the kind of muscle fiber, and it can be significantly improved by increasing the percentage of slow-twitch fibers. It is still not known which genes control the formation of muscle fibers or how those genes control the process of forming in sheep until now. In this study, we used high-throughput RNA sequencing to assess the expression profiles of coding and noncoding RNAs in muscle tissue of Tan sheep and Dorper sheep. To investigate the molecular processes involved in the formation of muscle fibers, we collected two different muscle tissues, longissimus dorsi and biceps femoris, from Tan sheep and Dorper sheep. The longissimus dorsi of Tan sheep and Dorper sheep displayed significantly differential expression levels for 214 lncRNAs, 25 mRNAs, 4 miRNAs, and 91 circRNAs. Similarly, 172 lncRNAs, 35 mRNAs, 12 miRNAs, and 95 circRNAs were differentially expressed in the biceps femoris of Tan sheep and Dorper sheep according to the expression profiling. GO and KEGG annotation revealed that these differentially expressed genes and noncoding RNAs were related to pathways of the formation of muscle fiber, such as the Ca2+, FoxO, and AMPK signaling pathways. Several key genes are involved in the formation of muscle fibers, including ACACB, ATP6V0A1, ASAH1, EFHB, MYL3, C1QTNF7, SFSWAP, and FBXL5. RT-qPCR verified that the expression patterns of randomly selected differentially expressed transcripts were highly consistent with those obtained by RNA sequencing. A total of 10 lncRNAs, 12 miRNAs, 20 circRNAs, and 19 genes formed lncRNA/circRNA-miRNA-gene networks, indicating that the formation of muscle fiber in Tan sheep is controlled by intricate regulatory networks of coding and noncoding genes. Our findings suggested that specific ceRNA subnetworks, such as circ_0017336-miR-23a-FBXL5, may be critical in the regulation of the development of muscle fibers, offering a valuable resource for future study of the development of muscle fibers in this animal species. The findings increase our understanding of the variety in how muscle fibers originate in various domestic animals and lay the groundwork for future research into new systems that regulate the development of muscle.

Genomic analyses of wild argali, domestic sheep, and their hybrids provide insights into chromosome evolution, phenotypic variation, and germplasm innovation.

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.

Improved Outcomes of Combined Main Branch Stenting and Side Branch Drug-Coated Balloon versus Two-Stent Strategy in Patients with Left Main Bifurcation Lesions.

BACKGROUND: Drug-eluting stent (DES) plus drug-coated balloon (DCB) is a safe and effective treatment strategy for coronary artery bifurcation lesions, but there is no report about this strategy being used for left main (LM) bifurcation lesions. We aim to explore the efficacy and safety of DES plus DCB in the treatment of LM bifurcation lesions. METHODS: A total of 100 patients diagnosed with LM bifurcation lesions by coronary angiography were retrospectively enrolled at our center from January 2018 to December 2019. They received either a two-stent strategy or a main branch (MB) stenting plus side branch (SB) DCB strategy and were accordingly divided into the 2-DES group and the DES + DCB group. Patients treated with DES + DCB were compared with a cohort of matched patients treated with a 2-DES strategy. Clinical data was collected and quantitative coronary analysis was performed. RESULTS: For immediate postoperative angiography, though the two groups had no differences in the minimal luminal diameter (MLD) and luminal stenosis of MB, the DES + DCB group had significantly lower SB ostial MLD and a higher degree of residual lumen stenosis than the 2-DES group (P < 0.05). At the time of follow-up, the SB ostial MLD of the DES + DCB group was higher than that of the 2-DES group, but lumen stenosis, late lumen loss (LLL), and LLL at the distal end of the left MB were all smaller than those of the 2-DES group (Ps < 0.05). Furthermore, the incidence of lumen restenosis and MACE between the two groups had no significance. CONCLUSION: The combination of DES and DCB is relatively safe and effective for the treatment of LM bifurcation lesions, and this strategy seems to have advantages in reducing LLL at the SB ostium.

Whole-Genome Resequencing of Worldwide Wild and Domestic Sheep Elucidates Genetic Diversity, Introgression, and Agronomically Important Loci.

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.

Adverse Cardiovascular Effects of Anti-COVID-19 Drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 infection is the cause of the ongoing global pandemic. Mortality from COVID-19 infection is particularly high in patients with cardiovascular diseases. In addition, COVID-19 patients with preexisting cardiovascular comorbidities have a higher risk of death. Main cardiovascular complications of COVID-19 are myocardial infarction, myocarditis, acute myocardial injury, arrhythmias, heart failure, stroke, and venous thromboembolism. Therapeutic interventions in terms of drugs for COVID-19 have many cardiac adverse effects. Here, we review the relative therapeutic efficacy and adverse effects of anti-COVID-19 drugs.

Genome-wide DNA arrays profiling unravels the genetic structure of Iranian sheep and pattern of admixture with worldwide coarse-wool sheep breeds.

Archaeological and genetic evidence show that sheep were originally domesticated in area around the North of Zagros mountains, North-west of Iran. The Persian plateau exhibits a variety of native sheep breeds with a common characteristic of coarse-wool production. Therefore, knowledge about the genetic structure and diversity of Iranian sheep and genetic connections with other sheep breeds is of great interest. To this end, we genotyped 154 samples from 11 sheep breeds distributed across Iran with the Ovine Infinium HD SNP 600 K BeadChip array, and analyzed this dataset combined with the retrieved data of 558 samples from 19 worldwide coarse-wool sheep breeds. The average genetic diversity ranged from 0.315 to 0.354, while the FST values ranged from 0.016 to 0.177 indicating a low differentiation of Iranian sheep. Analysis of molecular variance showed that 90.21 and 9.79% of the source of variation were related to differences within and between populations, respectively. Our results indicated that the coarse-wool sheep from Europe were clearly different from those of the Asia. Accordingly, the Asiatic mouflon was positioned between Asian and European countries. In addition, we found that the genetic background of Iranian sheep is present in sheep from China and Kyrgyzstan, as well as India. The revealed admixture patterns of the Iranian sheep and other coarse-wool sheep breeds probably resulted from the expansion of nomads and through the Silk Road trade network.

Genome-Wide Detection of Copy Number Variations and Their Association With Distinct Phenotypes in the World's Sheep.

Copy number variations (CNVs) are a major source of structural variation in mammalian genomes. Here, we characterized the genome-wide CNV in 2059 sheep from 67 populations all over the world using the Ovine Infinium HD (600K) SNP BeadChip. We tested their associations with distinct phenotypic traits by conducting multiple independent genome-wide tests. In total, we detected 7547 unique CNVs and 18,152 CNV events in 1217 non-redundant CNV regions (CNVRs), covering 245 Mb (∼10%) of the whole sheep genome. We identified seven CNVRs with frequencies correlating to geographical origins and 107 CNVRs overlapping 53 known quantitative trait loci (QTLs). Gene ontology and pathway enrichment analyses of CNV-overlapping genes revealed their common involvement in energy metabolism, endocrine regulation, nervous system development, cell proliferation, immune, and reproduction. For the phenotypic traits, we detected significantly associated (adjusted P < 0.05) CNVRs harboring functional candidate genes, such as SBNO2 for polycerate; PPP1R11 and GABBR1 for tail weight; AKT1 for supernumerary nipple; CSRP1, WNT7B, HMX1, and FGFR3 for ear size; and NOS3 and FILIP1 in Wadi sheep; SNRPD3, KHDRBS2, and SDCCAG3 in Hu sheep; NOS3, BMP1, and SLC19A1 in Icelandic; CDK2 in Finnsheep; MICA in Romanov; and REEP4 in Texel sheep for litter size. These CNVs and associated genes are important markers for molecular breeding of sheep and other livestock species.

Mitochondrial DNA Analysis Clarifies Taxonomic Status of the Northernmost Snow Sheep (Ovis nivicola) Population.

Currently, the intraspecific taxonomy of snow sheep (Ovis nivicola) is controversial and needs to be specified using DNA molecular genetic markers. In our previous work using whole-genome single nucleotide polymorphism (SNP) analysis, we found that the population inhabiting Kharaulakh Ridge was genetically different from the other populations of Yakut subspecies to which it was usually referred. Here, our study was aimed at the clarification of taxonomic status of Kharaulakh snow sheep using mitochondrial cytochrome b gene. A total of 87 specimens from five different geographic locations of Yakut snow sheep as well as 20 specimens of other recognized subspecies were included in this study. We identified 19 haplotypes, two of which belonged to the population from Kharaulakh Ridge. Median-joining network and Bayesian tree analyses revealed that Kharaulakh population clustered separately from all the other Yakut snow sheep. The divergence time between Kharaulakh population and Yakut snow sheep was estimated as 0.48 ± 0.19 MYA. Thus, the study of the mtDNA cytb sequences confirmed the results of genome-wide SNP analysis. Taking into account the high degree of divergence of Kharaulakh snow sheep from other groups, identified by both nuclear and mitochondrial DNA markers, we propose to classify the Kharaulakh population as a separate subspecies.

Liraglutide Attenuates Myocardial Fibrosis via Inhibition of AT1R-Mediated ROS Production in Hypertensive Mice.

BACKGROUND/AIMS: Glucagon-like peptide-1 receptor agonist liraglutide has been reported to exert cardioprotective effects, but its effect on cardiac fibrosis remains controversial. The aim of this study was to investigate the effects of liraglutide on cardiac fibrosis and potential mechanisms. METHODS: C57BL/6 mice (3-month old) were randomly divided into control, hypertension, and hypertension + liraglutide groups. The hypertensive state was created by infusion of Ang II (100 ng/kg·min) for 4 weeks through subcutaneously implanted osmotic pumps. The control mice were infused with saline. Mice were also given vehicle or liraglutide (400 µg/kg·day). Blood pressure (BP), blood sugar, myocardial fibrosis, AT1R expression, and reactive oxygen species (ROS) levels were measured. To further elucidate the mechanisms of fibrosis, mouse cardiac fibroblasts were isolated and treated with liraglutide (300 nM/L) or losartan (10 µM) for 3 hours, followed by Ang II (10-7 M) for additional 12 hours. Reactive oxygen species production and expressions of collagen-1 and -3 were measured. RESULTS: Liraglutide reduced BP and blood sugar but did not affect the body weight of the hypertensive mice. Liraglutide also inhibited collagen accumulation, AT1R expression, and ROS generation in the hearts of the hypertensive mice. In in vitro studies, pretreatment with liraglutide and losartan (as control) markedly inhibited Ang II-induced ROS production and collagen expression in the cultured cardiac fibroblasts. CONCLUSION: Liraglutide reduces myocardial fibrosis in the hypertensive mice, which appears to be dependent on at least in part inhibition of ROS production.

Historical Introgression from Wild Relatives Enhanced Climatic Adaptation and Resistance to Pneumonia in Sheep.

How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here, we conducted a comprehensive genomic analysis of diversity, interspecies introgression, and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600K and 50K genome-wide single nucleotide polymorphism data from 3,447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn, and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248,302,667-248,306,614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication.

Fasting Plasma Glucose and Coronary Heart Disease in a Rural Population of North Henan, China.

Even in individuals without diabetes, the incidence of coronary heart disease (CHD) increases with the rise in fasting plasma glucose (FPG); however, the threshold of FPG for CHD in rural areas of China is unclear. We retrospectively examined 2,987 people. Coronary angiography records were used to determine the presence of CHD as well as its severity. Risk factors for CHD and the relationship between different levels of FPG and CHD were analyzed. After adjusting for age, hypertension, dyslipidemia, smoking, drinking, chronic kidney disease, and previous ischemic stroke, the incidence of CHD in nondiabetic women began to increase when FPG exceeded 5.2 mmol/L (odds ratio (OR) = 1.438, 95% confidence interval (CI) = 1.099-1.880, p=0.008), and the degree of coronary artery lesions also became more severe (OR = 1.406, 95% CI = 1.107-1.788, p=0.005). However, no such correlations were found in nondiabetic men. In conclusion, among the nondiabetic women in rural areas of northern Henan, both the incidence of CHD and the severity of lesions increased when FPG levels were greater than 5.2 mmol/L, while no significant correlation between FPG and CHD was observed in diabetes-free men.

Paternal Origins and Migratory Episodes of Domestic Sheep.

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution.

CLEC3B protects H9c2 cardiomyocytes from apoptosis caused by hypoxia via the PI3K/Akt pathway.

Ischemic heart disease (IHD) is one of the leading causes of death worldwide. C-type lectin domain family 3 member B (CLEC3B) is a C-type lectin superfamily member and is reported to promote tissue remodeling. The serum levels of CLEC3B are downregulated in patients with cardiovascular disease. However, the molecular mechanisms of CLEC3B in IHD is not well-characterized. Therefore, we overexpressed CLEC3B and silenced CLEC3B in H9c2 rat cardiomyocytes for the first time. We then constructed a model of IHD in vitro through culturing H9c2 cardiomyocytes in serum-free medium under oxygen-deficit conditions. Then, Cell Counting Kit-8 (CCK-8), flow cytometry, qRT-PCR, and western blot assays were performed to investigate cell viability, apoptosis, and expression levels of CLEC3B, phosphatidylinositol 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (Akt), phosphorylated Akt (p-Akt), and cleaved-caspase 3. We observed that the mRNA expression of CLEC3B was decreased in hypoxic H9c2 cardiomyocytes (P<0.05). Overexpression of CLEC3B increased cell viability (P<0.01), inhibited cell apoptosis (P<0.05), upregulated the levels of p-PI3K/PI3K and p-Akt/Akt (P<0.01 or P<0.05), and downregulated expression of cleaved-caspase 3 (P<0.001) in hypoxic H9c2 cardiomyocytes while silencing of CLEC3B caused the opposite results. Inhibition of the PI3K/Akt pathway reversed the protective effect of CLEC3B on hypoxic H9c2 cardiomyocytes. Our study demonstrated that CLEC3B alleviated the injury of hypoxic H9c2 cardiomyocytes via the PI3K/Akt pathway.

Whole-genome resequencing of wild and domestic sheep identifies genes associated with morphological and agronomic traits.

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.