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    Co-expression of the SARS-CoV-2 entry molecules ACE2 and TMPRSS2 in human ovaries: Identification of cell types and trends with age

    Wu M.Ma L.Xue L.Zhu Q....
    12页
    查看更多>>摘要：? 2021The high rate of SARS-CoV-2 infection poses a serious threat to public health. Previous studies have suggested that SARS-CoV-2 can infect human ovary, the core organ of the female reproductive system. However, it remains unclear which type of ovarian cells are easily infected by SARS-CoV-2 and whether ovarian infectivity differs from puberty to menopause. In this study, public datasets containing bulk and single-cell RNA-Seq data derived from ovarian tissues were analyzed to demonstrate the mRNA expression and protein distribution of the two key entry receptors for SARS-CoV-2—angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2). Furthermore, an immunohistochemical study of ACE2 and TMPRSS2 in human ovaries of different ages was conducted. Differentially expressed gene (DEG) analysis of ovaries of different ages and with varying ovarian reserves was conducted to explore the potential functions of ACE2 and TMPRSS2 in the ovary. The analysis of the public datasets indicated that the co-expression of ACE2 and TMPRSS2 was observed mostly in oocytes and partially in granulosa cells. However, no marked difference was observed in ACE2 or TMPRSS2 expression between young and old ovaries and ovaries with low and high reserves. Correspondingly, ACE2 and TMPRSS2 were detected in the human ovarian cortex and medulla, especially in oocytes of different stages, with no observed variations in their expression level in ovaries of different ages, which was consistent with the results of bioinformatic analyses. Remarkably, DEG analysis showed that a series of viral infection-related pathways were more enriched in ACE2-positive ovarian cells than in ACE2-negative ovarian cells, suggesting that SARS-CoV-2 may potentially target specific ovarian cells and affect ovarian function. However, further fundamental and clinical research is still needed to monitor the process of SARS-CoV-2 entry into ovarian cells and the long-term effects of SARS-CoV-2 infection on the ovarian function in recovered females.
      原文链接:
    • NSTL
    • Elsevier

    HIV-1 Tat and cocaine impact astrocytic energy reservoir influence on miRNA epigenetic regulation

    Doke M.Kashanchi F.Khan M.A.Samikkannu T....
    15页
    查看更多>>摘要：? 2021 Elsevier Inc.Astrocytes are the primary regulator of energy metabolism in the central nervous system (CNS), and impairment of astrocyte's energy resource may trigger neurodegeneration. HIV infections and cocaine use are known to alter epigenetic modification, including miRNAs, which can target gene expression post-transcriptionally. However, miRNA-mediated astrocyte energy metabolism has not been delineated in HIV infection and cocaine abuse. Using next-generation sequencing (NGS), we identified a total of 1900 miRNAs, 64 were upregulated and 68 miRNAs were downregulated in the astrocytes by HIV-1 Tat with cocaine exposure. Moreover, miR-4727-3p, miR-5189-5p, miR-5090, and miR-6810-5p expressions were significantly impacted, and their gene targets were identified as VAMP2, NFIB, PPM1H, MEIS1, and PSD93 through the bioinformatic approach. In addition, the astrocytes treated with the nootropic drug piracetam protects these miRNAs. These findings provide evidence that the miRNAs in the astrocytes may be a potential biomarker and therapeutic target for HIV and cocaine abuse-induced neurodegeneration.
      原文链接:
    • NSTL
    • Elsevier

    Epigenetic differences in an identical genetic background modulate alternative splicing in A. thaliana

    Chaudhary S.Jabre I.Syed N.H.
    11页
    查看更多>>摘要：? 2021How stable and temperature-dependent variations in DNA methylation and nucleosome occupancy influence alternative splicing (AS) remains poorly understood in plants. To answer this, we generated transcriptome, whole-genome bisulfite, and MNase sequencing data for an epigenetic Recombinant Inbred Line (epiRIL) of A. thaliana at normal and cold temperature. For comparative analysis, the same data sets for the parental ecotype Columbia (Col-0) were also generated, whereas for DNA methylation, previously published high confidence methylation profiles of Col-0 were used. Significant epigenetic differences in an identical genetic background were observed between Col-0 and epiRIL lines under normal and cold temperatures. Our transcriptome data revealed that differential DNA methylation and nucleosome occupancy modulate expression levels of many genes and AS in response to cold. Collectively, DNA methylation and nucleosome levels exhibit characteristic patterns around intron-exon boundaries at normal and cold conditions, and any perturbation in them, in an identical genetic background is sufficient to modulate AS in Arabidopsis.
      原文链接:
    • NSTL
    • Elsevier

    Distinct transcriptomic profiles of na?ve CD4+ T cells distinguish HIV-1 infected patients initiating antiretroviral therapy at acute or chronic phase of infection

    Petkov S.Chiodi F.
    14页
    查看更多>>摘要：? 2021 The AuthorsWe analyzed the whole transcriptome characteristics of blood CD4+ T na?ve (TN) cells isolated from HIV-1 infected patients starting ART at acute (early ART = EA; n = 13) or chronic (late ART = LA; n = 11) phase of infection and controls (C; n = 15). RNA sequencing revealed 389 differentially expressed genes (DEGs) in EA and 810 in LA group in relation to controls. Comparison of the two groups of patients showed 183 DEGs. We focused on DEGs involved in apoptosis, inflammation and immune response. Clustering showed a poor separation of EA from C suggesting that these two groups present a similar transcriptomic profile of CD4+ TN cells. The comparison of EA and LA patients resulted in a high cluster purity revealing that different biological dysfunctions characterize EA and LA patients. The upregulated expression of several inflammatory chemokine genes distinguished the patient groups from C; CCL2 and CCL7, however, were downregulated in EA compared to LA patients. BCL2, an anti-apoptotic factor pivotal for na?ve T cell homeostasis, distinguished both EA and LA from C. The expression of several DEGs involved in different inflammatory processes (TLR4, PTGS2, RAG1, IFNA16) was lower in EA compared LA. We conclude that although the transcriptome of CD4+ TN cells isolated from patients initiating ART at acute infection reveals a more quiescent phenotype, the survival profile of these cells still appears to be affected. Our results show that the detrimental process of inflammation is under more efficient control in EA patients.
      原文链接:
    • NSTL
    • Elsevier

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

    Lv F.-H.Esmailizadeh A.Moosanezhad Khabisi M.Asadi Foozi M....
    11页
    查看更多>>摘要：? 2021 Elsevier Inc.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.
      原文链接:
    • NSTL
    • Elsevier

    Inhibited HDAC3 promotes microRNA-376c-3p to suppress malignant phenotypes of gastric cancer cells by reducing WNT2b

    Zhang L.Liu F.Meng Z.Luo Q....
    11页
    查看更多>>摘要：? 2021 Elsevier Inc.Objective: Our study aims to identify the impact of histone deacetylase 3 (HDAC3) and microRNA-376c-3p (miR-376c-3p) on gastric cancer (GC) by targeting wingless-type MMTV integration site family member 2b (WNT2b). Methods: Levels of miR-376c-3p, HDAC3 and WNT2b were assessed. GC cells were treated with altered HDAC3 or miR-376c-3p to evaluate their biological functions, and rescue experiment was performed to assess the effect of WNT2b on GC cells. The tumor growth in vivo was observed. Results: HDAC3 and WNT2b were up-regulated while miR-376c-3p was reduced in GC tissues and cell lines. The inhibited HDAC3 or elevated miR-376c-3p could restrain malignant behaviors of GC cells in vitro, and also suppress the xenograft growth. WNT2b silencing reduced the effect of miR-376c-3p inhibition while WNT2b overexpression mitigated that of miR-376c-3p promotion on GC cell growth. Conclusion: Inhibiting HDAC3 promotes miR-376c-3p to suppress malignant phenotypes of GC cells via reducing WNT2b, thereby restricting GC development.
      原文链接:
    • NSTL
    • Elsevier

    The global population structure and beta-lactamase repertoire of the opportunistic pathogen Serratia marcescens

    Matteoli F.P.Pedrosa-Silva F.Dutra-Silva L.Giachini A.J....
    10页
    查看更多>>摘要：? 2021 Elsevier Inc.Serratia marcescens is a global spread nosocomial pathogen. This rod-shaped bacterium displays a broad host range and worldwide geographical distribution. Here we analyze an international collection of this multidrug-resistant, opportunistic pathogen from 35 countries to infer its population structure. We show that S. marcescens comprises 12 lineages; Sm1, Sm4, and Sm10 harbor 78.3% of the known environmental strains. Sm5, Sm6, and Sm7 comprise only human-associated strains which harbor smallest pangenomes, genomic fluidity and lowest levels of core recombination, indicating niche specialization. Sm7 and Sm9 lineages exhibit the most concerning resistome; blaKPC-2 plasmid is widespread in Sm7, whereas Sm9, also an anthropogenic-exclusive lineage, presents highest plasmid/lineage size ratio and plasmid-diversity encoding metallo-beta-lactamases comprising blaNDM-1. The heterogeneity of resistance patterns of S. marcescens lineages elucidated herein highlights the relevance of surveillance programs, using whole-genome sequencing, to provide insights into the molecular epidemiology of carbapenemase producing strains of this species.
      原文链接:
    • NSTL
    • Elsevier

    Clustering genomic organization of sea cucumber miRNAs impacts their evolution and expression

    Liu C.Yuan J.Zhang X.Jin S....
    12页
    查看更多>>摘要：? 2021 Elsevier Inc.Echinoderms are marine deuterostomes with fascinating adaptation features such as aestivation and organ regeneration. However, post-transcriptional gene regulation by microRNAs (miRNAs) underlying these features are largely unexplored. Here, using homology-based and de novo approaches supported by expression data, we provided a comprehensive annotation of miRNA genes in the sea cucumber Apostichopus japonicus. By linkage and phylogenic analyses, we characterized miRNA genomic organization, evolutionary history and expression regulation. The results showed that sea cucumbers evolved a large number of new miRNAs, which tended to form polycistronic clusters via tandem duplication that had been especially active in the echinoderms. Most new miRNAs were weakly expressed, but miRNA clustering increased the expression level of clustered new miRNAs. The most abundantly expressed new miRNAs were organized in a single tandem cluster (cluster n2), which was activated during aestivation and intestine regeneration. Overall, our analyses suggest that clustering of miRNAs is important for their evolutionary origin, expression control, and functional cooperation.
      原文链接:
    • NSTL
    • Elsevier

    Decreased expression of HADH is related to poor prognosis and immune infiltration in kidney renal clear cell carcinoma

    Jiang H.Chen H.Wan P.Chen N....
    9页
    查看更多>>摘要：? 2021 Elsevier Inc.Kidney renal clear cell carcinoma (KIRC) is the subtype pf kidney cancer having the highest mortality as well as the highest potential of invasion and metastasis. The expression of HADH, encoding a key enzyme in fatty acid β-oxidation, has rarely been reported to correlate with prognosis and immune infiltration in cancers. This study aimed to explore the prognostic value of HADH in patients with KIRC. Gene expression profiles and clinical data of KIRC patients were acquired from The Cancer Genome Atlas. We compared the expression of HADH between KIRC tissues and normal tissues. Then, the relationship between HADH expression and the clinicopathological characteristics (survival, age, gender, stage, and grade) of KIRC was explored. Data from several online databases and paraffin-embedded specimens from two cohorts were used for external validation (10 cases from Meizhou People's Hospital and another 75 cases from a tissue chip, with both cohorts including KIRC samples and paired normal tissues). We also predicted the fractions of tumor-infiltrating immune cells (TIICs) in various tissues using CIBERSORT. Next, we estimated the prognostic value of differences in TIIC proportions between the high and low HADH expression groups. Finally, gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms by which HADH expression influences patient survival. The expression of HADH was significantly lower in KIRC tissue than in normal tissue. Decreased expression of HADH was significantly correlated with high histologic grade, advanced stage, and poor prognosis. The differential expression of HADH was validated at the protein level by immunohistochemistry. Multivariate Cox regression analysis indicated that HADH was an independent prognostic factor for KIRC. In addition, HADH expression was significantly associated with the accumulation of several TIICs, especially regulatory T cells. Finally, GSEA revealed that the transcriptome of the low HADH expression group was significantly enriched in genes involved in not only epithelial-mesenchymal transition and inflammatory response but also TNF-α, IL-6-JAK-STAT3, and interferon-γ signaling. In conclusion, our study demonstrated that decreased expression of HADH is related to poor prognosis and immune infiltration in KIRC; this finding may provide crucial information for the development of immunotherapies.
      原文链接:
    • NSTL
    • Elsevier

    Molecular mechanisms of mesocotyl elongation induced by brassinosteroid in maize under deep-seeding stress by RNA-sequencing, microstructure observation, and physiological metabolism

    Zhao X.Zhong Y.Zhou W.
    17页
    查看更多>>摘要：? 2021Deep-seeding is an important way to improve maize drought resistance, mesocotyl elongation can significantly enhance its seedling germination. To improve our understanding of transcription-mediated maize mesocotyl elongation under deep-seeding stress. RNA-sequencing was used to identify differentially expressed genes (DEGs) in both deep-seeding tolerant W64A and intolerant K12 mesocotyls following culture for 10 days after 2.0 mg·L?1 24-epibrassinolide (EBR) induced stress at the depths of 3 and 20 cm. Phenotypically, the mesocotyl length of both maize significantly increased under 20 cm stress and in the presence of EBR. Microstructure observations revealed that the mesocotyls underwent programmed cell death under deep-seeding stress, which was alleviated by EBR. This was found to be regulated by multiple DEGs encoding cysteine protease/senescence-specific cysteine protease, aspartic protease family protein, phospholipase D, etc. and transcription factors (TFs; MYB, NAC). Additionally, some DEGs associated with cell wall components, i.e., cellulose synthase/cellulose synthase like protein (CESA/CSL), fasciclin-like arabinogalactan (APG), leucine-rich repeat protein (LRR) and lignin biosynthesis enzymes including phenylalanine ammonia-lyase, S-adenosyl-L-methionine-dependent methyltransferases, 4-coumarate-CoA ligase, cinnamoyl CoA reductase, cinnamyl alcohol dehydrogenase, catalase, peroxiredoxin/peroxidase were found to control cell wall sclerosis. Moreover, in auxin, ethylene, brassinosteriod, cytokinin, zeatin, abscisic acid, gibberellin, jasmonic acid, and salicylic acid signaling transduction pathways, the corresponding DEGs were activated/inhibited by TFs (ARF, BZR1/2, B-ARR, A-ARR, MYC2, ABF, TGA) and synthesis of phytohormones-related metabolites. These findings provide information on the molecular mechanisms controlling maize deep-seeding tolerance and will aid in the breeding of deep-seeding maize varieties.
      原文链接:
    • NSTL
    • Elsevier