Ye Z

References (13)

Title : Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial - Wang_2024_Diabetes.Obes.Metab__
Author(s) : Wang W , Guo X , Zhang C , Ning T , Ma G , Huang Y , Jia R , Zhou D , Cao M , Zhang T , Yao L , Yuan J , Chen L , Wang Y , Jiang C , Dong X , Chen M , Gu Q , Zhang L , Fu Y , Pan T , Bi Y , Song W , Xu J , Lu W , Sun X , Ye Z , Zhang D , Peng L , Lin X , Dai W , Wang Q , Yang W
Ref : Diabetes Obes Metab , : , 2024
Abstract : AIM: This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS: This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS: Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS: For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.
ESTHER : Wang_2024_Diabetes.Obes.Metab__
PubMedSearch : Wang_2024_Diabetes.Obes.Metab__
PubMedID: 38221859 || 38618970

Title : Genome-Wide Identification and Characterization of Effector Candidates with Conserved Motif in Falciphora oryzae - Dai_2024_Int.J.Mol.Sci_25_
Author(s) : Dai M , Su Z , Zhu X , Li L , Ye Z , Tan X , Kong D , Liu X , Lin F
Ref : Int J Mol Sci , 25 : , 2024
Abstract : Microbes employ effectors to disrupt immune responses and promote host colonization. Conserved motifs including RXLR, LFLAK-HVLVxxP (CRN), Y/F/WxC, CFEM, LysM, Chitin-bind, DPBB_1 (PNPi), and Cutinase have been discovered to play crucial roles in the functioning of effectors in filamentous fungi. Nevertheless, little is known about effectors with conserved motifs in endophytes. This research aims to discover the effector genes with conserved motifs in the genome of rice endophyte Falciphora oryzae. SignalP identified a total of 622 secreted proteins, out of which 227 were predicted as effector candidates by EffectorP. By utilizing HMM features, we discovered a total of 169 effector candidates with conserved motifs and three novel motifs. Effector candidates containing LysM, CFEM, DPBB_1, Cutinase, and Chitin_bind domains were conserved across species. In the transient expression assay, it was observed that one CFEM and one LysM activated cell death in tobacco leaves. Moreover, two CFEM and one Chitin_bind inhibited cell death induced by Bax protein. At various points during the infection, the genes' expression levels were increased. These results will help to identify functional effector proteins involving omics methods using new bioinformatics tools, thus providing a basis for the study of symbiosis mechanisms.
ESTHER : Dai_2024_Int.J.Mol.Sci_25_
PubMedSearch : Dai_2024_Int.J.Mol.Sci_25_
PubMedID: 38203820

Title : Monovalent SARS-COV-2 mRNA vaccine using optimal UTRs and LNPs is highly immunogenic and broadly protective against Omicron variants - Ye_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2311752120
Author(s) : Ye Z , Bonam SR , McKay LGA , Plante JA , Walker J , Zhao Y , Huang C , Chen J , Xu C , Li Y , Liu L , Harmon J , Gao S , Song D , Zhang Z , Plante KS , Griffiths A , Hu H , Xu Q
Ref : Proc Natl Acad Sci U S A , 120 :e2311752120 , 2023
Abstract : The emergence of highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that are resistant to the current COVID-19 vaccines highlights the need for continued development of broadly protective vaccines for the future. Here, we developed two messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccines, TU88mCSA and ALCmCSA, using the ancestral SARS-CoV-2 spike sequence, optimized 5' and 3' untranslated regions (UTRs), and LNP combinations. Our data showed that these nanocomplexes effectively activate CD4(+) and CD8(+) T cell responses and humoral immune response and provide complete protection against WA1/2020, Omicron BA.1 and BQ.1 infection in hamsters. Critically, in Omicron BQ.1 challenge hamster models, TU88mCSA and ALCmCSA not only induced robust control of virus load in the lungs but also enhanced protective efficacy in the upper respiratory airways. Antigen-specific immune analysis in mice revealed that the observed cross-protection is associated with superior UTRs [Carboxylesterase 1d (Ces1d)/adaptor protein-3beta (AP3B1)] and LNP formulations that elicit robust lung tissue-resident memory T cells. Strong protective effects of TU88mCSA or ALCmCSA against both WA1/2020 and VOCs suggest that this mRNA-LNP combination can be a broadly protective vaccine platform in which mRNA cargo uses the ancestral antigen sequence regardless of the antigenic drift. This approach could be rapidly adapted for clinical use and timely deployment of vaccines against emerging and reemerging VOCs.
ESTHER : Ye_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2311752120
PubMedSearch : Ye_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2311752120
PubMedID: 38134199

Title : A universal GlycoDesign for lysosomal replacement enzymes to improve circulation time and biodistribution - Chen_2023_Front.Bioeng.Biotechnol_11_1128371
Author(s) : Chen YH , Tian W , Yasuda M , Ye Z , Song M , Mandel U , Kristensen C , Povolo L , Marques ARA , Caval T , Heck AJR , Sampaio JL , Johannes L , Tsukimura T , Desnick R , Vakhrushev SY , Yang Z , Clausen H
Ref : Front Bioeng Biotechnol , 11 :1128371 , 2023
Abstract : Currently available enzyme replacement therapies for lysosomal storage diseases are limited in their effectiveness due in part to short circulation times and suboptimal biodistribution of the therapeutic enzymes. We previously engineered Chinese hamster ovary (CHO) cells to produce alpha-galactosidase A (GLA) with various N-glycan structures and demonstrated that elimination of mannose-6-phosphate (M6P) and conversion to homogeneous sialylated N-glycans prolonged circulation time and improved biodistribution of the enzyme following a single-dose infusion into Fabry mice. Here, we confirmed these findings using repeated infusions of the glycoengineered GLA into Fabry mice and further tested whether this glycoengineering approach, Long-Acting-GlycoDesign (LAGD), could be implemented on other lysosomal enzymes. LAGD-engineered CHO cells stably expressing a panel of lysosomal enzymes [aspartylglucosamine (AGA), beta-glucuronidase (GUSB), cathepsin D (CTSD), tripeptidyl peptidase (TPP1), alpha-glucosidase (GAA) or iduronate 2-sulfatase (IDS)] successfully converted all M6P-containing N-glycans to complex sialylated N-glycans. The resulting homogenous glycodesigns enabled glycoprotein profiling by native mass spectrometry. Notably, LAGD extended the plasma half-life of all three enzymes tested (GLA, GUSB, AGA) in wildtype mice. LAGD may be widely applicable to lysosomal replacement enzymes to improve their circulatory stability and therapeutic efficacy.
ESTHER : Chen_2023_Front.Bioeng.Biotechnol_11_1128371
PubMedSearch : Chen_2023_Front.Bioeng.Biotechnol_11_1128371
PubMedID: 36911201

Title : Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via miR-5120\/ABHD6 - Li_2022_Drug.Des.Devel.Ther_16_3557
Author(s) : Li R , Ye Z , She D , Fang P , Zong G , Hu K , Kong D , Xu W , Li L , Zhou Y , Zhang K , Xue Y
Ref : Drug Des Devel Ther , 16 :3557 , 2022
Abstract : OBJECTIVE: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has been extensively studied, the role of its underlying pathogenesis remains unclear, and there is currently no approved therapeutic strategy for NAFLD. The purpose of this study was to observe the beneficial effects of Semaglutide on NAFLD in vivo and in vitro, as well as its potential molecular mechanisms. METHODS: Semaglutide was used to treat type 2 diabetes mellitus (T2DM) combined with NAFLD mice for 12 weeks. Hepatic function and structure were evaluated by liver function, blood lipids, liver lipids, H&E staining, oil red staining and Sirius staining. The expression of alpha/beta hydrolase domain-6 (ABHD6) was measured by qPCR and Western blotting in vivo and in vitro. Then, dual-luciferase reporter assay was performed to verify the regulation of the upstream miR-5120 on ABHD6. RESULTS: Our data revealed that Semaglutide administration significantly improved liver function and hepatic steatosis in T2DM combined with NAFLD mice. Furthermore, compared with controls, up-regulation of ABHD6 and down-regulation of miR-5120 were found in the liver of T2DM+NAFLD mice and HG+FFA-stimulated Hepa 1-6 hepatocytes. Interestingly, after Semaglutide intervention, ABHD6 expression was significantly decreased in the liver of T2DM+NAFLD mice and in HG+FFA-stimulated Hepa 1-6 hepatocytes, while miR-5120 expression was increased. We also found that miR-5120 could regulate the expression of ABHD6 in hepatocytes, while Semaglutide could modulate the expression of ABHD6 through miR-5120. In addition, GLP-1R was widely expressed in mouse liver tissues and Hepa 1-6 cells. Semaglutide could regulate miR-5120/ABHD6 expression through GLP-1R. CONCLUSION: Our data revealed the underlying mechanism by which Semaglutide improves hepatic steatosis in T2DM+NAFLD, and might shed new light on the pathological role of miR-5120/ABHD6 in the pathogenesis of T2DM+NAFLD.
ESTHER : Li_2022_Drug.Des.Devel.Ther_16_3557
PubMedSearch : Li_2022_Drug.Des.Devel.Ther_16_3557
PubMedID: 36238196

Title : Esterase-responsive and size-optimized prodrug nanoparticles for effective intracranial drug delivery and glioblastoma treatment - Ye_2022_Nanomedicine__102581
Author(s) : Ye Z , Gao L , Cai J , Wang Y , Li Y , Tong S , Yan T , Sun Q , Qi Y , Xu Y , Jiang H , Zhang S , Zhao L , Chen Q
Ref : Nanomedicine , :102581 , 2022
Abstract : Glioblastoma multiforme (GBM) is the intracranial malignancy with the highest rates of morbidity and mortality. Chemotherapy is often ineffective against GBM due to the presence of the blood-brain barrier (BBB); however, the application of nanotechnology is expected to overcome this limitation. Poly(lactic-co-glycolic acid) (PLGA) is a degradable and nontoxic functional polymer with good biocompatibility that is widely used in the pharmaceutical industry. Previous studies have shown that the ability of PLGA nanoparticles (NPs) to penetrate the BBB is largely determined by their size; however, determination of the optimal PLGA NP size requires further research. Here, we report a tandutinib-based prodrug (proTan), which responds to the GBM microenvironment, that was combined with NPs to overcome the BBB. AMD3100-PLGA NPs loaded with proTan inhibited tumor growth and effectively prolonged the survival of tumor-bearing mice.
ESTHER : Ye_2022_Nanomedicine__102581
PubMedSearch : Ye_2022_Nanomedicine__102581
PubMedID: 35811067

Title : Oligo(Lactic Acid)(8)-Docetaxel Prodrug-Loaded PEG-b-PLA Micelles for Prostate Cancer - Repp_2021_Nanomaterials.(Basel)_11_
Author(s) : Repp L , Unterberger CJ , Ye Z , Feltenberger JB , Swanson SM , Marker PC , Kwon GS
Ref : Nanomaterials (Basel) , 11 : , 2021
Abstract : Docetaxel (DTX) is among the most frequently prescribed chemotherapy drugs and has recently been shown to extend survival in advanced prostate cancer patients. However, the poor water solubility of DTX prevents full exploitation of this potent anticancer drug. The current marketed formulation, Taxotere((a)), contains a toxic co-solvent that induces adverse reactions following intravenous injection. Nano-sized polymeric micelles have been proposed to create safer, water-soluble carriers for DTX, but many have failed to reach the clinic due to poor carrier stability in vivo. In this study, we aimed to improve micelle stability by synthesizing an ester prodrug of DTX, oligo(lactic acid)(8)-docetaxel (o(LA)(8)-DTX), for augmented compatibility with the core of poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) micelles. Due to the enhancement of drug-carrier compatibility, we were able to load 50% (w/w) prodrug within the micelle, solubilize 20 mg/mL o(LA)(8)-DTX (~12 mg/mL DTX-equivalent) in aqueous media, and delay payload release. While the micelle core prohibited premature degradation, o(LA)(8)-DTX was rapidly converted to parent drug DTX through intramolecular backbiting (t(1/2) = 6.3 h) or esterase-mediated degradation (t(1/2) = 2.5 h) following release. Most importantly, o(LA)(8)-DTX micelles proved to be as efficacious but less toxic than Taxotere((a)) in a preclinical mouse model of prostate cancer.
ESTHER : Repp_2021_Nanomaterials.(Basel)_11_
PubMedSearch : Repp_2021_Nanomaterials.(Basel)_11_
PubMedID: 34685195

Title : Repurposing of Camptothecin: An Esterase-Activatable Prodrug Delivered by a Self-Emulsifying Formulation that Improves Efficacy in Colorectal Cancer - Fang_2021_Int.J.Pharm__120399
Author(s) : Fang T , Ye Z , Chen X , Wang Y , Wan J , Wang H
Ref : Int J Pharm , :120399 , 2021
Abstract : The global burden of colorectal cancer (CRC), the third most commonly diagnosed malignancy, continues to rise. Therefore, more effective and less toxic therapies are needed for CRC. CPT-11 (also called irinotecan), the standard-of-care treatment for CRC, has only had limited effects on survival outcomes. In vivo, CPT-11 must be converted to an active metabolite, SN38, to exert antitumor activity in the presence of carboxylesterases in vivo, but the conversion rate is extremely low (usually less than 8%). To fully harness the active SN38 compound, we showed here that esterification of SN38 using alpha-linolenic acid (LNA) generated a prodrug (termed LSN38), which can be formulated in pharmaceutically acceptable surfactants, such as polysorbate 80. Upon blending with an aqueous ethanolic solution, the mixture of LSN38/polysorbate 80 formed self-emulsifying nanomicelles (termed LSN38 NMs), enabling systemic injection. Unlike the insufficient release of active SN38 from CPT-11, drug activation from the LSN38 prodrug was quantitative and relied on esterase, which is abundant in cancerous cells. Pharmacokinetics studies revealed that polysorbate 80-based nanomicelles stably constrained the prodrug in the reservoir and prolonged blood circulation compared to CPT-11. Furthermore, LSN38 NMs showed superior therapeutic efficacy against a colorectal xenograft-bearing mouse model that failed to be treated with clinically approved CPT-11. Overall, these studies highlight the feasibility of converting a chemotherapeutic agent that is not miscible or compatible with pharmaceutical surfactants into an injectable self-emulsifying formulation. This approach could be applied to rescue other drugs or drug candidates that are abandoned in the preclinical stages due to pharmaceutical challenges.
ESTHER : Fang_2021_Int.J.Pharm__120399
PubMedSearch : Fang_2021_Int.J.Pharm__120399
PubMedID: 33647408

Title : The cross-sectional study of hepatic lipase SNPs and plasma lipid levels - Wei_2020_Food.Sci.Nutr_8_1162
Author(s) : Wei W , Hu T , Luo H , Ye Z , Lu F , Wu Y , Ying M
Ref : Food Sci Nutr , 8 :1162 , 2020
Abstract : By the combination of meta-analysis, the data of the 1,000 Genomes Project Phase 3, and the promoter sequence of hepatic lipase (LIPC), we performed the cross-sectional study to explore the associations of four variants (rs1077835; rs1077834; rs1800588 [C-514T], and rs2070895 [G-250A]) in LIPC promoter with plasma lipid levels. Our results indicate that the first and the next three of the four SNPs are, respectively, reported to be associated with the decreased and increased HDL-c level. Meta-analysis of 87 studies with 101,988 participants indicates that HDL-c level in rs1800588 (C-514T) (pooled mean difference = 0.03, 95%CI (0.03, 0.04), p < .001) and rs2070895 (G-250A) (pooled mean difference = 0.07, 95%CI (0.05, 0.09), p < .001) is higher in allele T or A carriers. Similarly, LDL-c, TC, TG, and BMI levels are generally increased in T or A alleles carriers. We failed to conduct the meta-analysis of rs1077835 and rs1077834 due to the limited previous reports. Data from the 1,000 Genomes indicate that the allele frequencies of the four SNPs in total or subpopulations are almost equal to each other. The paired value r (2) and D' of the four SNPs are larger than 0.8, which indicate the linkage disequilibrium of the four variants. The analysis of LIPC promoter indicate that C-514T and G-250A are, respectively, located in transcriptional factor binding sites of USF1and Pbx1b, which may partly explain the effect of the two SNPs on the decreased LIPC activity in the alleles carriers and the corresponding increased plasma lipids hydrolyzed by LIPC. These results may help us to better understand the different effects of the four SNPs on the plasma lipid levels among subpopulations and offer clues for future clinical treatment of dyslipidemia-related diseases.
ESTHER : Wei_2020_Food.Sci.Nutr_8_1162
PubMedSearch : Wei_2020_Food.Sci.Nutr_8_1162
PubMedID: 32341780

Title : Single-particle enumeration-based ultrasensitive enzyme activity quantification with fluorescent polymer nanoparticles - Han_2019_Nanoscale_11_14793
Author(s) : Han Y , Ye Z , Wang F , Chen T , Wei L , Chen L , Xiao L
Ref : Nanoscale , 11 :14793 , 2019
Abstract : Acetylcholinesterase (AChE) plays a vital role in nerve conduction through rapidly hydrolyzing the neurotransmitter acetylcholine (ACh) and is correlated with Alzheimer's disease. In this work, a label-free single-particle enumeration (SPE) method for the quantitative detection of acetylcholinesterase (AChE) activity is developed. The design is based on the fluorescence resonance energy transfer (FRET) between fluorescent conjugated polymer nanoparticles (FCPNPs) and MnO2 nanosheets. The fluorescence of FCPNPs can be effectively quenched by MnO2 nanosheets via hydrogen bonding interaction. In the presence of acetylcholinesterase (AChE), acetylthiocholine (ATCh) could be hydrolyzed to thiocholine (TCh), which can reduce MnO2 to Mn2+ and trigger the decomposition of MnO2 nanosheets. As a result, the fluorescence of FCPNPs is restored. Taking advantage of the superior brightness and stable fluorescence emission from individual FCPNPs, the accurate quantification of AChE is achieved by statistically counting the fluorescent particles on the glass slide surface. A linear range from 5 to 1600 muU mL-1 is obtained for AChE assay and the limit-of-detection (LOD) is 1.02 muU mL-1, which is far below the spectroscopic measurements in bulk solution. In the human serum sample, satisfactory recovery efficiencies are determined in a range of 91.0%-103.0%. Furthermore, pesticide carbaryl as an inhibitor of AChE activity was detected. The LOD is 1.12 pg mL-1 with linear responses ranging from 5 to 300 pg mL-1, which demonstrates the feasibility of this approach for AChE inhibitor screening. As a consequence, the label-free SPE-based method affords a promising platform for the sensitive detection of target molecules in the future.
ESTHER : Han_2019_Nanoscale_11_14793
PubMedSearch : Han_2019_Nanoscale_11_14793
PubMedID: 31353389

Title : Enzymatic synthesis and characterization of galactosyl monoesters - An_2015_Carbohydr.Res_414_32
Author(s) : An D , Zhao X , Ye Z
Ref : Carbohydr Res , 414 :32 , 2015
Abstract : Enzyme-catalyzed synthesis of several fatty acyl-amino acid esters based on D-galactose, as well as their chemical evaluation, was performed. These novel galactosyl fatty acyl-amino acid monoesters were synthesized by utilizing lipase from lipozyme TL IM in tert-butanol with D-galactose and fatty acyl-amino acids as starting materials. The products were characterized by (1)H NMR, (13)C NMR and MS analysis. In addition, their primary physical properties, such as hydrophilic-lipophilic balance (HLB), critical micellar concentration (CMC), solubility in water, maximum surface excess (gamma max), and minimal surface tension (Amin) were measured. The experimental results showed that their CMC values are between 5 and 0.4 mM. The HLB values of galactosyl esters 15-17 indicate that they are useful as oil-in-water emulsions or detergents, whereas 18-22 can be employed as water-in-oil emulsifiers or wetting agents.
ESTHER : An_2015_Carbohydr.Res_414_32
PubMedSearch : An_2015_Carbohydr.Res_414_32
PubMedID: 26172090

Title : N-myc downstream regulated gene 1 acts as a tumor suppressor in ovarian cancer - Wang_2014_Oncol.Rep_31_2279
Author(s) : Wang B , Li J , Ye Z , Li Z , Wu X
Ref : Oncol Rep , 31 :2279 , 2014
Abstract : Although implicated in a number of tumor types, the role of N-myc downstream regulated gene 1 (NDRG1) in ovarian cancer (OC) is unclear. In the present study, we used short hairpin RNA (shRNA) to silence NDRG1 in the OC cell line OVCAR3 and assessed the effect of its knockdown on cell morphology, proliferation, colony formation, migration and invasion. To complement these knockdown studies, we overexpressed NDRG1 in the same cell line. We found that NDRG1 knockdown significantly enhanced OVCAR3 proliferation, migration and invasion; however, there were no apparent changes in cell morphology. We also examined the effect in vivo and found that NDRG1 depletion promoted OVCAR3 xenograft growth in nude mice. In accordance with these data, we found that NDRG1 overexpression decreased proliferation, adhesion and apoptosis, and induced G0/G1 cell cycle arrest in OVCAR3 cells; expression of p21 and p53 was also increased. In conclusion, we demonstrated that NDRG1 acts as a tumor suppressor in ovarian carcinogenesis and may be a potential therapeutic target in this disease.
ESTHER : Wang_2014_Oncol.Rep_31_2279
PubMedSearch : Wang_2014_Oncol.Rep_31_2279
PubMedID: 24626771

Title : The yak genome and adaptation to life at high altitude - Qiu_2012_Nat.Genet_44_946
Author(s) : Qiu Q , Zhang G , Ma T , Qian W , Wang J , Ye Z , Cao C , Hu Q , Kim J , Larkin DM , Auvil L , Capitanu B , Ma J , Lewin HA , Qian X , Lang Y , Zhou R , Wang L , Wang K , Xia J , Liao S , Pan S , Lu X , Hou H , Wang Y , Zang X , Yin Y , Ma H , Zhang J , Wang Z , Zhang Y , Zhang D , Yonezawa T , Hasegawa M , Zhong Y , Liu W , Huang Z , Zhang S , Long R , Yang H , Lenstra JA , Cooper DN , Wu Y , Shi P , Liu J
Ref : Nat Genet , 44 :946 , 2012
Abstract : Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.
ESTHER : Qiu_2012_Nat.Genet_44_946
PubMedSearch : Qiu_2012_Nat.Genet_44_946
PubMedID: 22751099
Gene_locus related to this paper: bosmu-l8ic43 , bovin-2neur , bovin-balip , bovin-BCHE , bovin-e1bbv2 , bovin-e1bn79 , bovin-est8 , bovin-f1mi11 , bovin-f1n385 , bovin-g3mxp5 , bovin-lipli , bovin-lipr2 , bovin-q2kj30 , bovin-q3sz79 , bovin-q3t0r6 , bovin-ABHDA , bovin-q08dw9 , bovin-ABHD16B , bovin-SPG21 , bovin-TEX30 , 9ceta-l8iwv2 , 9ceta-l8idy3 , 9ceta-l8hsi3 , bovin-e1bjq9 , bovin-f1mc21 , 9ceta-l8hyl8 , bovin-LIPG , bovin-a0a3q1nm09 , bovin-f1n2i5