Federated Learning With Only Positive Labels by Exploring Label Correlations.

Federated learning (FL) aims to collaboratively learn a model by using the data from multiple users under privacy constraints. In this article, we study the multilabel classification (MLC) problem under the FL setting, where trivial solution and extremely poor performance may be obtained, especially when only positive data with respect to a single class label is provided for each client. This issue can be addressed by adding a specially designed regularizer on the server side. Although effective sometimes, the label correlations are simply ignored and thus suboptimal performance may be obtained. Besides, it is expensive and unsafe to exchange user's private embeddings between server and clients frequently, especially when training model in the contrastive way. To remedy these drawbacks, we propose a novel and generic method termed federated averaging (FedAvg) by exploring label correlations (FedALCs). Specifically, FedALC estimates the label correlations in the class embedding learning for different label pairs and utilizes it to improve the model training. To further improve the safety and also reduce the communication overhead, we propose a variant to learn fixed class embedding for each client, so that the server and clients only need to exchange class embeddings once. Extensive experiments on multiple popular datasets demonstrate that our FedALC can significantly outperform the existing counterparts.

Inhibition of SMAD3 effectively reduces ADAMTS-5 expression in the early stages of osteoarthritis.

OBJECTIVE: As one of the most important protein-degrading enzymes, ADAMTS-5 plays an important role in the regulation of cartilage homeostasis, while miRNA-140 is specifically expressed in cartilage, which can inhibit the expression of ADAMTS-5 and delay the progression of OA (osteoarthritis). SMAD3 is a key protein in the TGF-ß signaling pathway, inhibiting the expression of miRNA-140 at the transcriptional and post-transcriptional levels, and studies have confirmed the high expression of SMAD3 in knee cartilage degeneration, but whether SMAD3 can mediate the expression of miRNA-140 to regulate ADAMTS-5 remains unknown. METHODS: Sprague-Dawley (SD) rat chondrocytes were extracted in vitro and treated with a SMAD3 inhibitor (SIS3) and miRNA-140 mimics after IL-1 induction. The expression of ADAMTS-5 was detected at the protein and gene levels at 24 h, 48 h, and 72 h after treatment. The OA model of SD rats was created using the traditional Hulth method in vivo, with SIS3 and lentivirus packaged miRNA-140 mimics injected intra-articularly at 2 weeks, 6 weeks and 12 weeks after surgery. The expression of miRNA-140 and ADAMTS-5 in the knee cartilage tissue was observed at the protein and gene levels. Concurrently, knee joint specimens were fixed, decalcified, and embedded in paraffin prior to immunohistochemical, Safranin O/Fast Green staining, and HE staining analyses for ADAMTS-5 and SMAD3. RESULTS: In vitro, the expression of ADAMTS-5 protein and mRNA in the SIS3 group decreased to different degrees at each time point. Meanwhile, the expression of miRNA-140 in the SIS3 group was significantly increased, and the expression of ADAMTS-5 in the miRNA-140 mimics group was also significantly downregulated (P < 0.05). In vivo, it was found that ADAMTS-5 protein and gene were downregulated to varying degrees in the SIS3 and miRNA-140 mimic groups at three time points, with the most significant decrease at the early stage (2 weeks) (P < 0.05), and the expression of miRNA-140 in the SIS3 group was significantly upregulated, similar to the changes detected in vitro. Immunohistochemical results showed that the expression of ADAMTS-5 protein in the SIS3 and miRNA-140 groups was significantly downregulated compared to that in the blank group. The results of hematoxylin and eosin staining showed that in the early stage, there was no obvious change in cartilage structure in the SIS3 and miRNA-140 mock groups. The same was observed in the results of Safranin O/Fast Green staining; the number of chondrocytes was not significantly reduced, and the tide line was complete. CONCLUSION: The results of in vitro and in vivo experiments preliminarily showed that the inhibition of SMAD3 significantly reduced the expression of ADAMTS-5 in early OA cartilage, and this regulation might be accomplished indirectly through miRNA-140.

The clinical characteristics of anemia in native adults living at different altitudes of the Tibetan Plateau.

To provide evidence-based medicine references for formulating prevention and control policies in plateau areas, we explore the characteristics of anemia patients in Tibet (the plateau areas of China), especially those located at an altitude above 4500 m. We collected clinical data from 379 Tibetan anemia patients over the age of 18 years. We found those female patients accounted for the majority of Tibetan anemia patients. Almost half of the anemia patients aged from 28 to 47 years. The percentage of severe anemia and extremely severe anemia was 45.4% and 2.4%, respectively. 88.7% of patients are engaged in agriculture and animal husbandry, and 81.5% of patients just graduated from primary school or below. The most common causes of anemia were nutritional anemia, especially iron-deficiency anemia. At high-altitude localities, folic acid-deficiency anemia needs more attention. Overall, this study showed that altitude influences the incidence, severity, and cause of anemia. Peasants and herdsmen, low education levels, young and middle-aged women, and nutrition status should be paid attention to in future anemia control.

Activation of HIF-1α/VEGF-A pathway by deferoxamine ameliorates retinal hypoxia in a rat subarachnoid hemorrhage model.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is associated with sustained vasoconstriction in retinal vessels and vasoconstriction leads to retinal ischemia and hypoxia. Our previous finding also revealed the changes in hypoxia-related elements in the retina after SAH, further lending weight to the hypothesis that retinal vasospasm and hypoxia after SAH. Deferoxamine is a high-affinity iron chelator with reported neuroprotective effects against stroke. Here, we aimed to explore the effects of deferoxamine on retinal hypoxia after SAH. METHODS: SAH was established and deferoxamine was injected intraperitoneally for 3 days in the treatment group. To detect retinal new vessels, platelet endothelial cell adhesion molecule (CD31) was labeled by immunofluorescence and immunohistochemistry. Furthermore, the effects of deferoxamine on the expression of vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) were revealed by western blot analysis. RESULTS: The immunofluorescence and immunohistochemical staining of CD31 revealed a marked increase in new vessels in the retinal ganglion cell layer after deferoxamine treatment. By western blot analysis, HIF-1α and VEGF-A increased gradually in the first day and then rebounded to a new level on day 7. A deferoxamine-induced increase in HIF-1α/VEGF-A expression was also confirmed by western blot. CONCLUSIONS: Our findings suggest that modulating the application of deferoxamine may offer therapeutic approaches to alleviate retinal complications after SAH.

Dynamics of apoptosis-related gene expression during follicular development in yak.

The potential reproduction power of domestic animals is limited by a complicated follicular atresia process. P53, caspase-9 (Casp9), Bax, Bcl-2 and Fas play a crucial role in the ovarian mitochondrion-dependent apoptosis and death receptor pathway. In accordance with this study, the expression levels of Casp9, Bax, Bcl-2 and Fas were analysed in ovaries and oviducts of yak by immunohistochemistry (IHC). P53 and the above in ovarian granulosa cells (GCs) from atretic (3-6 mm) to healthy follicles (6-8 mm) and in oviducts were examined from the luteal phase to the follicular phase during the oestrous circle by Western blot (WB) and real-time PCR (RT-PCR). Results demonstrated that typical classic apoptotic factors Casp9, Bax, Bcl-2 and Fas were expressed in the cytoplasm and zonal pellucida of oocytes, primordial follicles, primary follicles, ovarian surface epithelium, ovarian GCs, granular lutein cells, surface epithelia in oviduct uterotubal junction and oviduct ampulla during the luteal phase. RT-PCR and WB revealed that P53 and Fas significantly increased in GCs of atretic follicles. P53 and Casp9 increased in oviduct epithelium during the luteal phase, but Fas was unchanged. A contrary tendency was noted in Bcl-2 and Bax expression. Overall, P53 and Fas play an essential role in inducing GC apoptosis, and Bax, Bcl-2, Casp9 and P53 are involved in oviduct epithelial regeneration in yak.

Deferoxamine reduces amyloid-beta peptides genesis and alleviates neural apoptosis after traumatic brain injury.

Traumatic brain injury (TBI) is recognized as the most influential risk factor for neurodegenerative diseases later in life, including Alzheimer's disease. The aberrant genesis of amyloid-ß peptides, which is triggered by TBI, is associated with the development of Alzheimer's disease. Evidence suggests that iron plays a role in both the production of amyloid-ß and its neurotoxicity, and iron overload has been noted in the brain after TBI. We therefore investigated the effects of an iron-chelating treatment on amyloid-ß genesis in a weight-drop model of TBI in mice. Human brain samples were obtained from patients undergoing surgery for severe brain trauma. The Institute of Cancer Research mice were treated with deferoxamine by intraperitoneal injection after TBI induction. Changes in amyloid-ß(1-42) were assessed using western blot and immunohistochemical staining. Ferritin was also detected using western blot to investigate iron deposition in the mice brain. Immunofluorescent terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was also performed to evaluate neural apoptosis. The amyloid-ß(1-42) was markedly elevated after TBI in both humans and mice. Deferoxamine treatment in mice significantly decreased the levels of both amyloid-ß(1-42) and ferritin in the brain, and reduced TBI-induced neural cell apoptosis. The iron chelator deferoxamine can alleviate the increase of amyloid-ß(1-42) in the brain after TBI, and may therefore be a potential therapeutic strategy to prevent TBI patients from undergoing neurodegenerative processes.

Comparative and selection sweep analysis of CNV was associated to litter size in Dazu black goats.

This study aims to identify the relative Copy number variation (CNV) associated with the litter size of Dazu black goats based on the unpublished CNV analytical results of our previously published sequencing data, in which the litter-size groups were classified into extreme low- and high-yield groups. Firstly, to compare the existence of valuable CNV in Dazu black goats with different fertility levels with mixed pools. We obtained 4992 and 4888 CNVs from the HY and LY, which overlapping 1461 genes, and classified on the original CNV type. Three genes [LOC108633278, PPP1R12A, and YIPF4] were observed in the intersection between the HY deletion and the LY duplication groups. Secondly, on individuals level, we identified a novel candidate CNV (Chr1_50215501, FST = 0.148, VST = 0.347) from 214 autosomal credible CNVs to be significant with litter size in the Dazu black goat, which located in the CBLB gene. This finding indicates the CBLB gene may affect the litter size of the Dazu black goats through structural variations, and Chr1_50215501 can be an effective genetic marker for marker-assisted selection breeding, and this study was also helps understand the molecular mechanism related to the goat litter size.

Retinal hypoxia after experimental subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The patients who survive subarachnoid hemorrhage (SAH) often have long-term neurological complications. There are no reports about the pathological change of retina after SAH. METHODS: An experimental model of SAH was established by injecting autologous blood into the prechiasmatic cistern of Sprague-Dawley rats. Hematoxylin and eosin (HE) staining was performed to show the alternation of morphology in retina after SAH. To detect the retinal new vessels (NVs), CD31 was labelled by immunofluorescence and immunohistochemistry. The time-course expressions of vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1α (HIF-1 α) was also revealed by Western blot analysis. RESULTS: A clear reduction of retinal ganglion cells (RGCs) was noticed after SAH. The immunofluorescence and immunohistochemical staining of CD31 reveals a large number of NVs in RGC layer after SAH compared with the normal controls. The level of VEGF-A in the retina after SAH was increased and peaked at 12h and 14 d. The expression of HIF-1α in the retina increased as early as 3 h after SAH, reached a peak at 12 h after SAH. CONCLUSIONS: The results showed that SAH induced the retina hypoxia resulting in the reduction of RGCs, increase of NVs and activation of NVs related HIF-1α/VEGF-A pathway.

Therapeutic Erythrocytapheresis Is Effective in Treating High Altitude Polycythemia on the Qinghai-Tibet Plateau.

INTRODUCTION: High altitude polycythemia (HAPC) is a common chronic disease at high altitudes. It is characterized by excessive erythrocytosis (≥190 g·L-1 in females or ≥210 g·L-1 in males). HAPC severely jeopardizes the health status of plateau dwellers. The Qinghai-Tibet plateau, with an elevation above 4000 m, is the highest plateau in the world. Both Han and Tibetan populations residing there face the threat of HAPC. Therapeutic erythrocytapheresis (TE) was introduced to Tibet as an alternative to phlebotomy in 2015. METHODS: In this study, we retrospectively analyzed 155 patients with HAPC treated with TE in Tibet. Routine blood testing values before and after TE were compared to evaluate treatment efficacy. The efficiency rate, defined as the rate of increase in red blood cell depletion attained by TE compared with 450 mL whole blood phlebotomy, was calculated using whole blood volume and hematocrit before and after treatment and used to identify patients who maintained a normal hemoglobin level in the year after the TE procedure. RESULTS: On average, TE reduced red blood cell levels by 1.5×1012·L-1, hemoglobin concentration by 52 g·L-1, and hematocrit by 14% (P<0.001 for each). Patients who underwent TE with an efficiency rate ≥1.9 were more likely to maintain a normal hemoglobin level in the following year than those who underwent TE with an efficiency rate <1.9 (90 vs 28%, P<0.01). CONCLUSIONS: TE is a feasible therapeutic method to treat HAPC on the Qinghai-Tibet plateau. The efficiency rate is a useful tool to predict the expected interval between TE procedures.

Neuroprotective role of glutathione peroxidase 4 in experimental subarachnoid hemorrhage models.

BACKGROUND AND PURPOSE: Early brain injury is an essential pathological process after subarachnoid hemorrhage (SAH), with many cell death modalities. Ferroptosis is a newly discovered regulated cell death caused by the iron-dependent accumulation of lipid peroxidation, which can be prevented by glutathione peroxidase 4 (GPX4). Our study aimed to investigate the role of GPX4 in neuronal cell death after experimental SAH. METHODS: In vivo experimental SAH was induced by injecting autologous arterial blood into the prechiasmatic cistern in male Sprague-Dawley rats. Meanwhile, the in vitro SAH model was performed with primary rat cortical neurons cultured in medium containing hemoglobin (Hb). Adenovirus was used to overexpress GPX4 before experimental SAH. GPX4 expression was detected by western blot and immunofluorescence experiments. Malondialdehyde (MDA) was measured to evaluate the level of lipid peroxidation. Nissl staining was employed to assess cell death in vivo, whereas lactate dehydrogenase (LDH) release was used to evaluate cell damage in vitro. The brain water content and neurological deficits were evaluated to determine brain injury. RESULTS: Endogenous GPX4 was mainly expressed in neurons, and its expression decreased at 24 h after experimental SAH. Overexpression of GPX4 significantly reduced lipid peroxidation and cell death in the experimental SAH models both in vivo and in vitro. Moreover, overexpression of GPX4 ameliorated brain edema and neurological deficits at 24 h after SAH. CONCLUSIONS: The decrease of GPX4 expression potentially plays an important role in ferroptosis during early brain injury after SAH. Overexpression of GPX4 has a neuroprotective effect after SAH.

SNP of AHSA2 gene in three cattle breeds using snapshot technology.

Droughtmaster is a tropical breed of beef cattle that can survive in hot climates and easily adapt to torrid environments. These traits are important in livestock breeding. In this study, we genotyped five single-nucleotide polymorphisms (SNPs) of the AHSA2 gene from 190 cattle belonging to three different breeds (Droughtmaster, Angus and Simmental) by using snapshot technology. This work aimed to identify the valuable molecular marker of heat resistance in cattle. Results showed that Droughtmaster exhibited higher expected heterozygosity and polymorphic information content compared with the two other breeds. The AHSA2-1 locus deviated from the Hardy-Weinberg equilibrium in the Droughtmaster breed (P < 0.05). Two SNPs in Droughtmaster diverged significantly from Angus and Simmental. The SNPs were identified as AHSA2-3 and AHSA2-4, which were closely linked to the three breeds based on pair-wise FST. AHSA2-4 involved a missense mutation. In summary, the GG genotypes in AHSA2-3 and AHSA2-4 may be candidate genotypes associated with heat resistance traits and may serve as valuable genetic markers for breeding of heat-tolerant beef cattle in the future.

Evolutionary relationship and population structure of domestic Bovidae animals based on MHC-linked and neutral autosomal microsatellite markers.

Major histocompatibility complex (MHC) genes are critical for disease resistance or susceptibility responsible for host-pathogen interactions determined mainly by extensive polymorphisms in the MHC genes. Here, we examined the diversity and phylogenetic pattern of MHC haplotypes reconstructed using three MHC-linked microsatellite markers in 55 populations of five Bovidae species and compared them with those based on neutral autosomal microsatellite markers (NAMs). Three-hundred-and-forty MHC haplotypes were identified in 1453 Bovidae individuals, suggesting significantly higher polymorphism and heterozygosity compared with those based on NAMs. The ambitious boundaries in population differentiation (phylogenetic network, pairwise FST and STRUCTURE analyses) within and between species assessed using the MHC haplotypes were different from those revealed by NAMs associated closely with speciation, geographical distribution, domestication and management histories. In addition, the mean FST was significantly correlated negatively with the number of observed alleles (NA), observed (HO) and expected (HE) heterozygosity and polymorphism information content (PIC) (P < 0.05) in the MHC haplotype dataset while there was no correction of the mean FST estimates (P> 0.05) between the MHC haplotype and NAMs datasets. Analysis of molecular variance (AMOVA) revealed a lower percentage of total variance (PTV) between species/groups based on the MHC-linked microsatellites than NAMs. Therefore, it was inferred that individuals within populations accumulated as many MHC variants as possible to increase their heterozygosity and thus the survival rate of their affiliated populations and species, which eventually reduced population differentiation and thereby complicated their classification and phylogenetic relationship inference. In summary, host-pathogen coevolution and heterozygote advantage, rather than demographic history, act as key driving forces shaping the MHC diversity within the populations and determining the interspecific MHC diversity.

Cross-talk between microRNA-let7c and transforming growth factor-ß2 during epithelial-to-mesenchymal transition of retinal pigment epithelial cells.

AIM: To explore the roles of microRNA-let7c (miR-let7c) and transforming growth factor-ß2 (TGF-ß2) and cellular signaling during epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial cells. METHODS: Retinal pigment epithelial (ARPE-19) cells were cultured with no serum for 12h, and then with recombinant human TGF-ß2 for different lengths of time. ARPE-19 cells were transfected with 1×106 TU/mL miR-let7c mimcs (miR-let7cM), miR-let7c mimcs negative control (miR-let7cMNC) and miR-let7c inhibitor (miR-let7cI) using the transfection reagent. The expression of keratin-18, vimentin, N-cadherin, IKB alpha, p65 were detected by Western blot, quantitative polymerase chain reaction and immunofluorescence. RESULTS: The expression of miR-let7c was dramatically reduced and the nuclear factor-kappa B (NF-κB) signaling pathway was activated after induction by TGF-ß2 (P<0.05). In turn, overexpressed miR-let7c significantly inhibited TGF-ß2-induced EMT (P<0.05). However, miR-let7c was unable to inhibit TGF-ß2-induced EMT when the NF-κB signaling pathway was inhibited by BAY11-7082 (P<0.01). CONCLUSION: The miR-let7c regulates TGF-ß2-induced EMT through the NF-κB signaling pathway in ARPE-19 cells.

Genome-wide selective sweep analysis of the high-altitude adaptability of yaks by using the copy number variant.

The domestic yak (Bos grunniens) from the Qinghai-Tibet Plateau is an important animal model in high-altitude adaptation studies. Here, we performed the genome-wide selective sweep analysis to identify the candidate copy number variation (CNV) for the high-altitude adaptation of yaks. A total of 531 autosomal CNVs were determined from 29 yak genome-wide resequencing data (15 high- and 14 low-altitude distributions) by using a CNV caller with a CNV identification interval > 5 kb, CNV silhouette score > 0.7, and minimum allele frequency > 0.05. Most high-frequency CNVs were located at the exonic (44.63%) and intergenic (46.52%) regions. In accordance with the results of the selective sweep analysis, 7 candidate CNVs were identified from the interaction of the top 20 CNVs with highest divergence from the F ST and V ST between the low (LA) and high (HA) altitudes. Five genes (i.e., GRIK4, IFNLR1, LOC102275985, GRHL3, and LOC102275713) were also annotated from the seven candidate CNVs and their upstream and downstream ranges at 300 kb. GRIK4, IFNLR1, and LOC102275985 were enriched in five known signal pathways, namely, glutamatergic synapse, JAK-STAT signaling pathway, cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and olfactory transduction. These pathways are involved in the environmental adaptability and various physiological functions of animals, especially the physiological regulation under a hypoxic environment. The results of this study advanced the understanding of CNV as an important genomic structure variant type that contributes to HA adaptation and helped further explain the molecular mechanisms underlying the altitude adaptability of yaks.

FOXO4 expression associates with glioblastoma development and FOXO4 expression inhibits cell malignant phenotypes in vitro and in vivo.

BACKGROUND AND AIM: Forkhead box protein O4 (FOXO4) is a transcription factor, and aberrant FOXO4 expression is associated with development of various human cancers. This study explored the role of FOXO4 in glioma in vitro and in vivo. METHODS: FOXO4 expression was first assessed in normal brain tissues, low-grade glioma, glioblastoma multiforme (GBM), normal human astrocytes (HA), and GBM cell lines, while manipulation of FOXO4 expression in glioma cell lines was assessed using qRT-PCR, Western blot, and cell viability CCK-8, Transwell, and a nude mouse subcutaneous xenograft assays. KEY FINDINGS: The data showed downregulated FOXO4 expression in GBM tissues and cell lines. FOXO4 overexpression induced by transfection with FOXO4 cDNA significantly inhibited GBM cell proliferation, migration, and invasion, but increased tumor cells to undergo apoptosis in vitro, while suppressed growth of GBM cell subcutaneous xenografts in nude mice. In conclusion, FOXO4 possesses an anti-cancer glioma activity, which could be a novel target for future control of GBM.

The role of mechanical stretch and TGF-ß2 in epithelial-mesenchymal transition of retinal pigment epithelial cells.

AIM: To explore the effects and mechanisms of mechanical stress and transforming growth factor-beta2 (TGF-ß2) on epithelial-mesenchymal transition (EMT) in cultured human retinal pigment epithelial (RPE) cells. METHODS: Human RPE cells were inoculated on BioFex 6-well plates and RPE cells received 0, 1, 2, 3, or 4 mild stretch injuries delivered 3h apart after 24h of culture. The device of mechanical stress parameters were set to sine wave, frequency 1 Hz, stretch strength 20%. For treatment with TGF-ß2, when the inoculated RPE cells in 6-well plates were around 60% confluent, serum was reduced to 0 for 12h and recombinant human TGF-ß2 (0, 1, 5, 10 ng/mL) was added for 48h. α-SMA, Vimentin and N-Cadherin, fibronectin proteins expressions were detected by Western blotting, confocal cell immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR). Then we detected the change of miRNA-29b and ascertained the changes of phosphatidylinositol 3-kinase-serine threonine protein kinase (PI3K/Akt) pathway after RPE cells were stretched by the device of mechanical stress and induced by TGF-ß2 by Western blotting, confocal cell immunofluorescence and qRT-PCR. RESULTS: Mechanical stress induce EMT and activate the PI3K/Akt pathway in ways that lead to the EMT process. TGF-ß2 induce RPE cells EMT and in a certain range and TGF-ß2 decrease the miRNA-29b expression in RPE cells, and the inhibitory effect is more obvious with the increase of TGF-ß2 concentration. CONCLUSION: Our findings are crucial steps in determining the critical roles of the PI3K/Akt signaling pathway and miRNA-29b in pathogenesis of proliferative vitreoretinopathy (PVR) which may be a potential target for preventing or treating PVR.

Genome-wide selection signatures analysis of litter size in Dazu black goats using single-nucleotide polymorphism.

Litter size is considered to be the most important index for estimating domestic animal productivity. The number of indigenous goats in China with higher litter sizes than those of commercial breeds in other countries may be helpful for accelerating genetic improvements in goat breeding. We performed a genome-wide selective sweep analysis of 31 Dazu black goats with extreme standard deviation in litter size within the third fetus to identify significant genomic regions and candidate genes through different analyses. The analysis identified a total of 33,917,703 variants, including 32,262,179 SNPs and 1,655,524 indels. In addition, two novel candidate genes (LRP1B and GLRB), which are related to litter size, were obtained with π, Tajima's D, πA/πB, and F ST at the individual level with a 95% threshold for each parameter. These two genes were annotated in five GO terms (localization, binding, macromolecular complex, membrane part, and membrane) and two pathways (long-term depression and neuroactive ligand-receptor interaction pathway). Regarding the result of linkage disequilibrium (LD) analysis, in LRP1B and GRID2, the high-yield Dazu black goats exhibit significantly different LD patterns from low-yield goats. Litter size variability has low heritability and is related to multiple complex factors found in domestic animals. Obtaining a clear explanation and significant signal by genome-wide selective sweep analysis with a small sample size is difficult. However, we investigated some candidate genes, particularly LRP1B and GLRB, which may provide useful information for further research.

Whole-genome analysis identifying candidate genes of altitude adaptive ecological thresholds in yak populations.

The domestic yak (Bos grunniens) is an iconic symbol of animal husbandry on the Qinghai-Tibet Plateau. Long-term domestication and natural selection have led to a wide distribution of yak, forming many ecological populations to adapt to the local ecological environment. High altitude is closely related to oxygen density, and it is an important environmental ecological factor for biological survival and livestock production. The aim of the present study was to perform a preliminary analysis to identify the candidate genes of altitude distribution adapted ecological thresholds in yak using next-generation sequence technology. A total of 15,762,829 SNPs were obtained from 29 yaks with high- and low-altitude distribution by genome-wide sequencing. According to the results of the selective sweep analysis with FST and ZHp, 21 candidate genes were identified. 14 genes (serine/threonine protein kinase TNNI3K, TEN1, DYM, ITPR1, ZC4H2, KNTC1, ADGRB3, CLYBL, TANGO6, ASCC3, KLHL3, PDE4D, DEPDC1B and AGBL4) were grouped into 32 Gene Ontology terms, and four genes (RPS6KA6, ITPR1, GNAO1 and PDE4D) annotated in 35 pathways, including seven environmental information processing and one environmental adaptation. Therefore, the novel candidate genes found in the current study do not only support new theories about high-altitude adaptation, but also further explain the molecular mechanisms of altitude adaptation threshold in yaks.