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1.
2.
Genome Biol ; 21(1): 46, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093779

RESUMO

Following publication of the original paper [1], the authors reported an error in the affiliation of Xin-Tian Hu, who is also affiliated with "Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China".

3.
Infect Genet Evol ; 81: 104181, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31918040

RESUMO

Avian influenza A viruses (AIVs) classify into 18 hemagglutinin (HA) and 11 neuraminidase (NA) subtypes. Even though H1N1 and H3N2 subtypes usually circulate among humans leading to infection, occasionally, H5, H6, H7, H9, and H10 that circulate in poultry also infect humans, and especially H5N1 and H7N9. Efficient virus replication is a critical factor that influences infection. Codon usage of a virus must coevolve with its host for efficient viral replication, therefore, we conduct a comprehensive analysis of codon usage bias in human-isolated AIVs to test their adaptation to host expression system. The relative synonymous codon usage (RSCU) pattern, and the codon adaptation index (CAI) are calculated for this purpose. We find that all human-isolated AIVs tend to eliminate GC and CpG compositions, which may prevent activation of the host innate immune system. Although codon usage differs between AIV subtypes, our data support the conclusion that natural selection has played a major role and mutation pressure a minor role in shaping codon usage bias in all AIVs. Our efforts discover that codon usage of genes encoding surface proteins of H5N1, and the polymerase genes of H7N9 has better fit to the human expression system. This may associate with their better replication and infection in human.

4.
G3 (Bethesda) ; 10(2): 515-524, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31792005

RESUMO

Reduced numbers of carpal and tarsal bones (wrist and ankle joints) are extensively observed in the clade of Cetacea and Ruminantia (Cetruminantia). Homebox D11 (Hoxd11) is one of the important genes required for limb development in mammals. Mutations in Hoxd11 can lead to defects in particular bones of limbs, including carpus and tarsus. To test whether evolutionary changes in Hoxd11 underlie the loss of these bones in Cetruminantia, we sequenced and analyzed Hoxd11 coding sequences and compared them with other 5' HoxA and HoxD genes in a taxonomic coverage of Cetacea, Ruminantia and other mammalian relatives. Statistical tests on the Hoxd11 sequences found an accelerated evolution in the common ancestor of cetaceans and ruminants, which coincided with the reduction of carpal and tarsal bones in this clade. Five amino acid substitutions (G222S, G227A, G229S, A240T and G261V) and one amino acid deletion (G254Del) occurred in this lineage. In contrast, other 5' HoxA and HoxD genes do not show this same evolutionary pattern, but instead display a highly conserved pattern of evolution in this lineage. Accelerated evolution of Hoxd11, but not other 5' HoxA and HoxD genes, is probably related to the reduction of the carpal and tarsal bones in Cetruminantia. Moreover, we found two amino acid substitutions (G110S and D223N) in Hoxd11 that are unique to the lineage of Cetacea, which coincided with hindlimb loss in the common ancestor of cetaceans. Our results give molecular evidence of Hoxd11 adaptive evolution in cetaceans and ruminants, which could be correlated with limb morphological adaptation.

7.
Int J Mol Med ; 45(1): 10-22, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746376

RESUMO

Ovarian cancer has a high rate of recurrence, with M2 macrophages having been found to be involved in its progression and metastasis. To examine the relationship between macrophages and ovarian cancer in the present study, M0 macrophages were stimulated with apoptotic SKOV3 cells and it was found that these macrophages promoted tumor proliferation and migration. Subsequently, the mRNAs and proteins expressed at high levels in these M2 macrophages were examined by RNA­Seq and quantitative proteomics, respectively, which revealed that M0 macrophages stimulated by apoptotic SKOV3 cells also expressed M2 markers, including CD206, interleukin­10, C­C motif chemokine ligand 22, aminopeptidase­N, disabled homolog 2, matrix metalloproteinase 1 and 5'­nucleotidase. The abundance of phosphorylated Erk1/2 in these macrophages was increased. The results indicate that apoptotic SKOV3 cells stimulate M0 macrophages to differentiate into M2 macrophages by activating the ERK pathway. These results suggest possible treatments for patients with ovarian cancer who undergo chemotherapy; inhibiting M2 macrophage differentiation during chemotherapy may reduce the rate of tumor recurrence.

8.
Gene ; 728: 144296, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31866555

RESUMO

Insulin and glucagon are important hormones for regulating blood glucose levels. Rodents are useful models for understanding human physiology, however, differences exist between rodents and humans. Here I examined the evolution of the genes encoding insulin (Ins) and glucagon (Gcg, which also encodes GLP-1 and GLP-2) and the receptors for these hormones (Insr, Gcgr, Glp1r, and Glp2r). Our results show that the insulin 1 gene (Ins1) that originated by retroposition in some rodents such as mice, experienced selective constraints that are as strong as those acting upon the Ins2 gene found in the locus-of-origin. Previous studies had shown that the insulin hormones and genes in hystricomorph rodents, such as the guinea pig, have altered function and selective constraints, respectively. Here I show that the insulin receptor genes in hystricomorph rodents also experienced changes in evolutionary rates, but that these changes did not alter sites involved in hormone binding. While glucagon, but not GLP-1 and GLP-2, in hystricomorph rodents also show increased rates of sequence evolution, no changes in the evolution of the glucagon receptor gene (Gcgr) was seen. Intriguingly, the GLP2 receptor gene (Glp2r) in mice-like rodents evolved more rapidly than those in hystricomorph rodents. When the rates of evolution of the genes encoding the receptors for proglucagon-derived peptides, which are all G-protein coupled receptors, were compared, the GLP-1 receptor gene (Glp1r) was found to display increased levels of sequence constraint compared to the Gcgr and Glp2r genes.


Assuntos
Evolução Molecular , Glucagon/genética , Insulina/genética , Receptor de Insulina/genética , Receptores de Glucagon/genética , Roedores/genética , Animais , Genoma , Filogenia
10.
Genome Biol ; 20(1): 258, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779658

RESUMO

BACKGROUND: Brain aging is a complex process that depends on the precise regulation of multiple brain regions; however, the underlying molecular mechanisms behind this process remain to be clarified in non-human primates. RESULTS: Here, we explore non-human primate brain aging using 547 transcriptomes originating from 44 brain areas in rhesus macaques (Macaca mulatta). We show that expression connectivity between pairs of cerebral cortex areas as well as expression symmetry between the left and right hemispheres both decrease after aging. Although the aging mechanisms across different brain areas are largely convergent, changes in gene expression and alternative splicing vary at diverse genes, reinforcing the complex multifactorial basis of aging. Through gene co-expression network analysis, we identify nine modules that exhibit gain of connectivity in the aged brain and uncovered a hub gene, PGLS, underlying brain aging. We further confirm the functional significance of PGLS in mice at the gene transcription, molecular, and behavioral levels. CONCLUSIONS: Taken together, our study provides comprehensive transcriptomes on multiple brain regions in non-human primates and provides novel insights into the molecular mechanism of healthy brain aging.

11.
Peptides ; : 170158, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31582191

RESUMO

Glucose-dependent insulinotropic polypeptide (GIP) is a product of the Gip gene and acts as an incretin hormone in mammals. Gip is most closely related to the proglucagon (Gcg) and Exendin genes and diverged from these very early in vertebrate evolution. In mammals, GIP acts through its specific receptor, encoded by the Gipr gene, which belongs to a subfamily of 7-transmembrane G-protein coupled receptor (GPCR) genes that also includes those for the proglucagon-derived peptides (Gcgr, Glp1r, and Glp2r), and the receptor for Exendin (Grlr). Gip, Gipr, Exendin, and Grlr genes are found in species from most vertebrate classes. While most species that have a Gip gene also have a Gipr gene, two classes of vertebrates, cartilaginous fish and birds, retain conserved Gip genes but lack Gipr genes. This raises the possibility the GIP signals through other receptors in some vertebrates. Exendin genes and the gene for its receptor, Grlr, are also found in diverse vertebrates, with the notable exception of mammals. Both GIP and Exendin likely have important roles in vertebrate physiology, but their roles are either dispensable or can be replaced by other hormones.

12.
Stem Cell Res Ther ; 10(1): 302, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623669

RESUMO

BACKGROUND: A refractory wound is a typical complication of diabetes and is a common outcome after surgery. Current approaches have difficulty in improving wound healing. Recently, non-expanded stromal vascular fraction (SVF), which is derived from mature fat, has opened up new directions for the treatment of refractory wound healing. The aim of the current study is to systematically investigate the impact of SVF on wound healing, including the rate and characteristics of wound healing, ability of fibroblasts to migrate, and blood transport reconstruction, with a special emphasis on their precise molecular mechanisms. METHODS: SVF was isolated by digestion, followed by filtration and centrifugation, and then validated by immunocytochemistry, a MTS proliferation assay and multilineage potential analysis. A wound model was generated by creating 6-mm-diameter wounds, which include a full skin defect, on the backs of streptozocin-induced hyperglycemic mice. SVF or human adipose-derived stem cell (hADSC) suspensions were subcutaneously injected, and the wounds were characterized over a 9-day period by photography and measurements. A scratch test was used to determine whether changes in the migratory ability of fibroblasts occurred after co-culture with hADSCs. Angiogenesis was observed with human umbilical vein endothelial cells. mRNA from fibroblasts, endotheliocyte, and skin tissue were sequenced by high-throughput RNAseq, and differentially expressed genes, and pathways, potentially regulated by SVF or hADSCs were bioinformatically analyzed. RESULTS: Our data show that hADSCs have multiple characteristics of MSC. SVF and hADSCs significantly improved wound healing in hyperglycemic mice. hADSCs improve the migratory ability of fibroblasts and capillary structure formation in HUVECs. SVF promotes wound healing by focusing on angiogenesis and matrix remodeling. CONCLUSIONS: Both SVF and hADSCs improve the function of fibroblast and endothelial cells, regulate gene expression, and promote skin healing. Various mechanisms likely are involved, including migration of fibroblasts, tubulogenesis of endothelial cells through regulation of cell adhesion, and cytokine pathways.

13.
J Mol Evol ; 87(9-10): 309-316, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31506780

RESUMO

In mammals, chicken-type (c-type) lysozymes are part of the innate immune system, killing bacteria by degrading peptidoglycan in their cell walls. Many of the studies on the evolution of c-type lysozymes have focused on its new digestive function, including the duplicated stomach lysozymes in ruminants. Similarly, in bats, gene duplications and subsequent adaptive evolution of c-type lysozyme have been reported in a clade of insectivorous species, which might have been driven by the need to digest chitin. However, no studies on the evolution of c-type lysozyme have been carried out in the second largest and dietary diverse bat family Phyllostomidae, which includes insectivorous, frugivorous, nectarivorous and sanguivorous species. Here, we sequenced and analyzed c-type lysozyme genes from four phyllostomid bats, the common vampire bat, the white-winged vampire bat, the lesser long-nosed bat and the big fruit-eating bat. Only a single lysozyme gene was identified in each of these species. Evidence for positive selection on mature lysozyme was found on lineages leading to vampire bats, but not other bats with single copy lysozyme genes. Moreover, several amino acid substitutions found in mature lysozymes from the sanguivorous clade are predicted to have functional impacts, adding further evidence for the adaptive evolution of lysozyme in vampire bats. Functional adaptation of vampire bat lysozymes could be associated with anti-microbial defense, possibly driven by the specialized sanguivory-related habits of vampire bats.

15.
Sci Rep ; 9(1): 11463, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391504

RESUMO

Tibetan pig is native to the Qinghai-Tibet Plateau and has adapted to the high-altitude environmental condition such as hypoxia. However, its origin and genetic mechanisms underlying high-altitude adaptation still remain controversial and enigmatic. Herein, we analyze 229 genomes of wild and domestic pigs from Eurasia, including 63 Tibetan pigs, and detect 49.6 million high-quality variants. Phylogenomic and structure analyses show that Tibetan pigs have a close relationship with low-land domestic pigs in China, implying a common domestication origin. Positively selected genes in Tibetan pigs involved in high-altitude physiology, such as hypoxia, cardiovascular systems, UV damage, DNA repair. Three of loci with strong signals of selection are associated with EPAS1, CYP4F2, and THSD7A genes, related to hypoxia and circulation. We validated four non-coding mutations nearby EPAS1 and CYP4F2 showing reduced transcriptional activity in Tibetan pigs. A high-frequency missense mutation is found in THSD7A (Lys561Arg) in Tibetan pigs. The selective sweeps in Tibetan pigs was found in association with selection against non-coding variants, indicating an important role of regulatory mutations in Tibetan pig evolution. This study is important in understanding the evolution of Tibetan pigs and advancing our knowledge on animal adaptation to high-altitude environments.

16.
Endocrinology ; 160(10): 2326-2327, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369078
17.
J Cancer ; 10(13): 2892-2906, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281466

RESUMO

Exosomes have recently become the subject of increasing research interest. Interactions between tumor and host cells via exosomes play crucial roles in the initiation, progression and invasiveness of breast cancer. In our study, we used exosomes isolated from a co-culture model of THP-1-derived macrophages exposed to apoptotic MCF-7 or MDA-MB-231 breast cancer cell line cells to investigate their effects on naïve MCF-7 or MDA-MB-231 cells in vitro and in vivo. This post-chemotherapy tumor microenvironment model allowed us to explore possible mechanisms that explain increased proliferation and metastasis of breast cancer seen in some patients. Our results suggest that while exosomes derived from macrophages normally inhibit proliferation and metastasis of MCF-7 or MDA-MB-231 cells, exposure of macrophages to breast cancer cells that have experienced chemotherapy are modified them to promote these processes. Exosomes from macrophages exposed to apoptotic cancer cells have increased amounts of IL-6 that increases the phosphorylation of STAT3, which likely explains the increased transcription of STAT3 target genes such as CyclinD1, MMP2 and MMP9. These observations suggest that the inhibition of exosome secretion and STAT3 signaling pathway activation might suppress the growth and metastasis of malignant tumors, and provide new targets for therapeutic treatment of malignant tumors after chemotherapy.

18.
Front Microbiol ; 10: 1328, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249566

RESUMO

Avian influenza A viruses (AIVs) H5N1, first identified in 1996, are highly pathogenic in domestic poultry and continue to occasionally infect humans. In this study, we sought to identify genetic changes that occurred during their multiple invasions to humans. We evaluated all available H5Nx AIV genomes. Significant signals of positive selection were detected in 29 host-shift branches. 126 parallel evolution sites were detected on these branches, including 17 well-known sites (such as T271A, A274T, T339M, Q591K, E627K, and D701N in PB2; A134V, D154N, S223N, and R497K in HA) that play roles in allowing AIVs to cross species barriers. Our study suggests that during human infections, H5Nx viruses have experienced adaptive evolution (positive selection and convergent evolution) that allowed them to adapt to their new host environments. Analyses of adaptive evolution should be useful in identifying candidate sites that play roles in human infections, which can be tested by functional experiments.

19.
Biotechnol Bioeng ; 116(10): 2652-2661, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31180145

RESUMO

A pyrogen test is crucial for evaluating the safety of drugs and medical equipment, especially those involved in injections. As existing pyrogen tests, including the rabbit pyrogen test, the limulus amoebocyte lysate (LAL) test and the monocyte activation test have limitations, development of new models for pyrogen testing is necessary. Here we develop a sensitive cell model for pyrogen test based on the lipopolysaccharides (LPS) signal pathway. TLR4, MD2, and CD14 play key roles in the LPS-mediated pyrogen reaction. We established a new TLR4/MD2/CD14-specific overexpressing knock-in cell model using the CRISPR/CAS9 technology and homologous recombination to detect LPS. Stimulation of our TLR4/CD14/MD2 knock-in cell line model with LPS leads to the release of the cytokines IL-6 and TNF-alpha, with a detection limit of 0.005 EU/ml, which is greatly lower than the lower limit of 0.015 EU/ml detected by the Tachypleus amebocyte lysate (TAL) assay.

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