scholarly journals Comparative analysis on lung transcriptome of Mycoplasma ovipneumoniae (Mo) - infected Bashbay sheep and argali hybrid sheep

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Zengqiang Li ◽  
Zhihui Du ◽  
Jie Li ◽  
Yanming Sun
Keyword(s):  
Lung Tissue ◽  
Post Infection ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Regulation Of Gene Expression ◽  
Protein Glycosylation ◽  
Control Group ◽  
Transcriptomic Response ◽  
Tissue Samples ◽  
Mycoplasma Ovipneumoniae

Abstract Background Bashbay sheep (Bbs) has a certain degree of resistance to Mycoplasma ovipneumoniae (Mo), however, Argali hybrid sheep (Ahs) is susceptible to Mo. To understand the molecular mechanisms underlying the difference of the susceptibility for Mo infection, RNA-sequencing technology was used to compare the transcriptomic response of the lung tissue of Mo-infected Bbs and Ahs. Results Six Bbs and six Ahs were divided into experimental group and control group respectively, all of them were experimentally infected with Mo by intratracheal injection. For collecting lung tissue samples, three Bbs and three Ahs were sacrificed on day 4 post-infection, and the others were sacrificed on day 14 post-infection. Total RNA extracted from lung tissue were used for transcriptome analyses based on high-throughput sequencing technique and bioinformatics. The results showed that 212 (146 up-regulated, 66 down-regulated) DEGs were found when comparing transcriptomic data of Bbs and Ahs at 4th dpi, besides, 311 (158 up-regulated, 153 down-regulated) DEGs were found at 14th dpi. After GO analysis, three main GO items protein glycosylation, immune response and positive regulation of gene expression were found related to Mo infection. In addition, there were 20 DEGs enriched in these above items, such as SPLUC1 (BPIFA1), P2X7R, DQA, HO-1 and SP-A (SFTPA-1). Conclusions These selected 20 DEGs associated with Mo infection laid the foundation for further study on the underlying molecular mechanism involved in high level of resistance to Mo expressed by Bbs, meanwhile, provided deeper understandings about the development of pathogenicity and host-pathogen interactions.

scholarly journals Identification of the Genetic Basis for the Large-tailed Phenotypic Trait in Han Sheep Through Integrated mRNA and miRNA Analysis of Tail Fat Tissue Samples

2020 ◽  
Author(s):  
Yang Guangli ◽  
Zhang Huan ◽  
Zhang Shuhong ◽  
Li Zhiqiang ◽  
Gao Fengyi ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Fat Deposition ◽  
Differentially Expressed ◽  
Future Research ◽  
Phenotypic Trait ◽  
Fatty Tissue ◽  
Fat Tissue ◽  
Tissue Samples

Abstract Background: While evolution has led certain breeds of sheep to exhibit large tails composed of fatty tissue, the genetic basis for this fatty large-tailed phenotypic trait remains to be defined in breeds of Han sheep. Here, we employed a high-throughput sequencing approach to identify mRNAs and microRNAs (miRNAs) that were differentially expressed in tail fat tissue samples from large-tailed Han (LTH) and small-tailed Han (STH) sheep in order to identify key genetic determinants of the large-tailed phenotype.Results: In total, we identified 521 mRNAs (237 upregulated, 284 downregulated) and 14 miRNAs (6 upregulated, 8 downregulated) that were differentially expressed between these two sheep breeds. Predictive analytical database tools were subsequently utilized to identify 2,409 putative targets of these differentially expressed miRNAs (DEMs), including 65 which were among the list of differentially expressed genes (DEGs) identified in the present study. By specifically focusing on predicted DEM/DEG pairs with appropriate regulatory directionality, we identified DIRF, HSD17B12, LPL, APOBR, INSIGI, THRSP, ACSL5, FAAH, ACSS2, APOA1, ACLY, and ACSM3 through mRNA analyses and ACSL4, FTO, FGF8, IGF2, GNPDA2, LIPG, PRKAA2, ELOVL7, SOAT2, and SIRT1 through miRNA analyses as candidate genes which may regulate fat deposition and fatty acid metabolism in the adipose tissue from the tails of Han sheep. Conclusion: Together, our data provide insight into the potential genetic basis for the large-tailed phenotype of LTH sheep, suggesting that it may be attributable to specific DEMs and DEGs that regulate one another and thereby control lipid metabolism. These data provide a basis for future research regarding the role of these genes in ovine tail fat deposition, and offer preliminary perspectives on the molecular mechanisms governing the fatty large-tailed phenotype in LTH sheep.

scholarly journals Landscape and dynamics of transcription initiation in the malaria parasitePlasmodium falciparum

2015 ◽  
Author(s):  
Sophie Adjalley ◽  
Christophe Chabbert ◽  
Bernd Klaus ◽  
Vicent Pelechano ◽  
Lars Steinmetz
Keyword(s):  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Regulation Of Gene Expression ◽  
Nucleotide Composition ◽  
Transcriptional Unit ◽  
Developmental Cycle ◽  
Transcription Start Sites ◽  
Sequencing Technologies ◽  
Nucleotide Resolution

The lack of a comprehensive map of transcription start sites (TSS) across the highly AT-rich genome ofP. falciparumhas hindered progress towards deciphering the molecular mechanisms that underly the timely regulation of gene expression in this malaria parasite. Using high-throughput sequencing technologies, we generated a comprehensive atlas of transcription initiation events at single nucleotide-resolution during the parasite intra-erythrocytic developmental cycle. This detailed analysis of TSS usage enabled us to define architectural features of plasmodial promoters. We demonstrate that TSS selection and strength are constrained by local nucleotide composition. Furthermore, we provide evidence for coordinate and stage-specific TSS usage from distinct sites within the same transcriptional unit, thereby producing transcript isoforms, a subset of which are developmentally regulated. This work offers a framework for further investigations into the interactions between genomic sequences and regulatory factors governing the complex transcriptional program of this major human pathogen.

scholarly journals Bovine milk somatic cell transcriptomic response to Staphylococcus aureus is dependent on strain genotype

2021 ◽  
Author(s):  
Dagmara Niedziela ◽  
Paul Cormican ◽  
Gilles Foucras ◽  
Finola Leonard ◽  
Orla Keane
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Somatic Cell ◽  
Post Infection ◽  
Molecular Mechanisms ◽  
Clinical Signs ◽  
Differentially Expressed ◽  
Composition Analysis ◽  
Transcriptomic Response ◽  
M1 Macrophages

AbstractBackgroundMastitis is an economically important disease of dairy cows with Staphylococcus aureus a major cause worldwide. Challenge of Holstein-Friesian cows demonstrated that a strain belonging to Clonal Complex (CC)151 caused clinical mastitis, while a strain belonging to CC97 caused mild or subclinical mastitis. The aim of this study was to elucidate the molecular mechanisms of the host immune response utilising a transcriptomic approach. Milk somatic cells from cows infected with each strain of S. aureus at 0, 24, 48, 72 and 168 hours post-infection (hpi) were analysed for differentially expressed (DE) genes in response to each strain.ResultsIn response to MOK023 (CC97), 1278, 2278, 1986 and 1750 significant differentially expressed (DE) genes were found at 24, 48, 72 and 168 hpi, respectively, while 2293, 1979, 1428 and 1544 significant DE genes were found in response to MOK124 (CC151) at those time points. Genes involved in milk production (CSN1, CSN10, CSN1S2, CSN2, a-LACTA and PRLR) were downregulated in response to both strains, with a more pronounced decrease in the MOK124 group. Immune response pathways such as NF-κB and TNF signalling were overrepresented in response to both strains at 24 hpi. These immune pathways continued to be overrepresented in the MOK023 group at 48 and 72 hpi, while the Hippo signalling, extracellular matrix interaction (ECM) and tight junction pathways were overrepresented in the MOK124 group between 48 and 168 hpi. Cellular composition analysis demonstrated that a neutrophil response was predominant in response to MOK124, while M1 macrophages were the main milk cell type post-infection in the MOK023 group.ConclusionsA switch from immune response pathways to pathways involved in maintaining the integrity of the epithelial cell layer was observed in the MOK124 group from 48 hpi, which coincided with the occurrence of clinical signs in the infected animals. The higher proportion of M1 macrophages in the MOK023 group and lack of substantial neutrophil recruitment in response to MOK023 may indicate immune evasion by this strain. The results of this study highlight that the somatic cell transcriptomic response to S. aureus is dependent on the genotype of the infecting strain.

scholarly journals Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality

2021 ◽  
Author(s):  
Anshul Budhraja ◽  
Anubhav Basu ◽  
Atish Gheware ◽  
Dasari Abhilash ◽  
Seesandra Rajagopala ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Complement Activation ◽  
Molecular Mechanisms ◽  
Metabolic Reprogramming ◽  
Lung Damage ◽  
Molecular Signature ◽  
Lung Pathology ◽  
Tissue Samples ◽  
Drug Molecules ◽  
The Status

The precise molecular mechanisms behind severe life-threatening lung abnormalities during severe SARS-CoV-2 infections are still unclear. To address this challenge, we performed whole transcriptome sequencing of lung autopsies from 31 patients suffering from severe COVID-19 related complications and 10 uninfected controls. Using a metatranscriptome analysis of lung tissue samples we identified the existence of two distinct molecular signatures of lethal COVID-19. The dominant "classical" signature (n=23) showed upregulation of unfolded protein response, steroid biosynthesis and complement activation supported by massive metabolic reprogramming leading to characteristic lung damage. The rarer signature (n=8) potentially representing "Cytokine Release Syndrome" (CRS) showed upregulation of IL1 cytokines such CCL19 but absence of complement activation and muted inflammation. Further, dissecting expression of individual genes within enriched pathways for patient signature suggests heterogeneity in host response to the primary infection. We found that the majority of patients cleared the SARS-CoV-2 infection, but all suffered from acute dysbiosis with characteristic enrichment of opportunistic pathogens such as Gordonia bronchialis in "classical" patients and Staphylococcus warneri in CRS patients. Our results suggest two distinct models of lung pathology in severe COVID-19 patients that can be identified through the status of the complement activation, presence of specific cytokines and characteristic microbiome. This information can be used to design personalized therapy to treat COVID-19 related complications corresponding to patient signature such as using the identified drug molecules or mitigating specific secondary infections.

Expression of long non-coding RNAs ROR and MALAT1 in uterine fibroids

2021 ◽  
Vol 20 (4) ◽  
pp. 17-21
Author(s):  
S.A. Levakov ◽  
◽  
G.Ya. Azadova ◽  
A.E. Mamedova ◽  
Kh.R. Movtaeva ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Uterine Fibroids ◽  
Reproductive Age ◽  
Expression Level ◽  
Control Group ◽  
Tissue Samples ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Objective. To study the expression level of long non-coding RNAs ROR and MALAT1 in tissue samples of uterine fibroids. Patients and methods. Samples of myomatous nodes and tissues of normal myometrium in 28 women of reproductive age were examined. The analysis of the expression of long non-coding RNAs was carried out using a real-time reverse-transcription polymerase chain reaction (RT-PCR) with specific primers. Results. There was a significant decrease in the expression level of long non-coding RNA ROR and an increase in the MALAT1 expression in tissue samples of uterine fibroids relative to the control group. Conclusion. The results obtained demonstrate a possible role of long non-coding RNAs in the development of uterine fibroids and correlate with the data which we obtained for patients with endometriosis. Detecting the expression level of long non-coding RNAs can improve the existing methods for diagnosing this disease. However, further research is required to determine the clinical significance of MALAT1 and ROR, and the molecular mechanisms underlying the action of these RNAs in uterine fibroid cells. Key words: long non-coding RNAs, uterine fibroids, myomectomy, lncROR, MALAT1

scholarly journals The impact of sex on gene expression across human tissues

Science ◽  
2020 ◽  
Vol 369 (6509) ◽  
pp. eaba3066 ◽  
Author(s):  
Meritxell Oliva ◽  
Manuel Muñoz-Aguirre ◽  
Sarah Kim-Hellmuth ◽  
Valentin Wucher ◽  
Ariel D. H. Gewirtz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Molecular Mechanisms ◽  
Genome Wide Association Study ◽  
Genetic Regulation ◽  
Regulation Of Gene Expression ◽  
Tissue Expression ◽  
Study Data ◽  
Tissue Samples ◽  
The Impact

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.

scholarly journals Bovine milk somatic cell transcriptomic response to Staphylococcus aureus is dependent on strain genotype

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Dagmara A. Niedziela ◽  
Paul Cormican ◽  
Gilles Foucras ◽  
Finola C. Leonard ◽  
Orla M. Keane
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Somatic Cell ◽  
Post Infection ◽  
Molecular Mechanisms ◽  
Bovine Milk ◽  
Clinical Signs ◽  
Composition Analysis ◽  
Transcriptomic Response ◽  
M1 Macrophages

Abstract Background Mastitis is an economically important disease of dairy cows with Staphylococcus aureus a major cause worldwide. Challenge of Holstein-Friesian cows demonstrated that S. aureus strain MOK124, which belongs to Clonal Complex (CC)151, caused clinical mastitis, while strain MOK023, belonging to CC97, caused mild or subclinical mastitis. The aim of this study was to elucidate the molecular mechanisms of the host immune response utilising a transcriptomic approach. Milk somatic cells were collected from cows infected with either S. aureus MOK023 or MOK124 at 0, 24, 48, 72 and 168 h post-infection (hpi) and analysed for differentially expressed (DE) genes in response to each strain. Results In response to MOK023, 1278, 2278, 1986 and 1750 DE genes were found at 24, 48, 72 and 168 hpi, respectively, while 2293, 1979, 1428 and 1544 DE genes were found in response to MOK124 at those time points. Genes involved in milk production (CSN1, CSN10, CSN1S2, CSN2, a-LACTA and PRLR) were downregulated in response to both strains, with a more pronounced decrease in the MOK124 group. Immune response pathways such as NF-κB and TNF signalling were overrepresented in response to both strains at 24 hpi. These immune pathways continued to be overrepresented in the MOK023 group at 48 and 72 hpi, while the Hippo signalling, extracellular matrix interaction (ECM) and tight junction pathways were overrepresented in the MOK124 group between 48 and 168 hpi. Cellular composition analysis demonstrated that a neutrophil response was predominant in response to MOK124, while M1 macrophages were the main milk cell type post-infection in the MOK023 group. Conclusions A switch from immune response pathways to pathways involved in maintaining the integrity of the epithelial cell layer was observed in the MOK124 group from 48 hpi, which coincided with the occurrence of clinical signs in the infected animals. The higher proportion of M1 macrophages in the MOK023 group and lack of substantial neutrophil recruitment in response to MOK023 may indicate immune evasion by this strain. The results of this study highlight that the somatic cell transcriptomic response to S. aureus is dependent on the genotype of the infecting strain.

scholarly journals Study on Intervention Mechanism of Yiqi Huayu Jiedu Decoction on ARDS Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Xu Liang ◽  
Changyong Luo ◽  
Yan Li ◽  
Xin Li ◽  
Qian Wang ◽  
...  
Keyword(s):  
Western Blot ◽  
Lung Tissue ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Expression Level ◽  
Network Pharmacology ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Protective Effects ◽  
Lung Tissue Damage

Background. Yiqi Huayu Jiedu (YQHYJD) is a traditional Chinese medicine decoction made up of eight traditional Chinese medicines. Although YQHYJD is effectively used to prevent and treat ARDS/acute lung injury (ALI) in rats, the molecular mechanisms supporting its clinical application remain elusive. The purpose of the current study was to understand its lung protective effects at the molecular level using network pharmacology approach. Methods. In an ARDS animal model, the beneficial pharmacological activities of YQHYJD were confirmed by reduced lung tissue damage levels observed on drug treated rats versus control group. We then proposed a network analysis to discover the key nodes based on drugs and disease network. Subsequently, we analyzed interaction networks and screened key targets. Using Western blot to detect the expression level of key targets, the intervention effect of changes in expression level of key targets on ARDS was evaluated. Results. Pathway enrichment analysis of highly ranked genes showed that ErbB pathways were highly related to ARDS. Finally, western blot results showed decreased level of the AKT1 and KRAS/NRAS/HRAS protein in the lung after treatment which confirmed the hypothesis. Conclusion. In conclusion, our results suggest that YQHYJD can exert lung tissue protective effect against the severe injury through multiple pathways, including the endothelial cells permeability improvement, inflammatory reaction inhibition, edema, and lung tissue hemorrhage reduction.

Changes in lung eicosanoid content during normal and abnormal transition in perinatal lambs

1992 ◽  
Vol 262 (2) ◽  
pp. L214-L222 ◽  
Author(s):  
S. H. Abman ◽  
K. R. Stenmark
Keyword(s):  
Pulmonary Hypertension ◽  
Cesarean Section ◽  
Lung Tissue ◽  
Fetal Lung ◽  
Late Gestation ◽  
Control Group ◽  
Potential Contribution ◽  
Tissue Samples ◽  
Cesarean Section Delivery ◽  
Hypertensive Group

To study the potential contribution of eicosanoids in maintaining high vascular tone in utero or in modulating resistance during the normal or abnormal transition of the pulmonary circulation, we performed serial measurements of hemodynamic parameters and lung eicosanoid content in perinatal sheep with and without pulmonary hypertension. Prostacyclin (6-keto-PGF1 alpha), thromboxane (TxB2), and leukotriene contents were measured in fetal lung liquid (FLL), bronchoalveolar lavage fluid (BALF), and lung tissue samples. Leukotriene content was barely detectable above background in FLL samples from 11 late-gestation fetuses, and lung leukotriene content in fetal lung was one-third of that measured in maternal lung (P less than 0.01). Tissue samples from serial lung biopsies obtained before and after cesarean-section delivery of late-gestation lambs demonstrated increased lung prostacyclin content after delivery (P less than 0.04), but no changes in total leukotriene or thromboxane contents were found. In an experimental model of perinatal pulmonary hypertension, prostanoid and leukotriene content of FLL obtained immediately before delivery were not different from an age-matched nonhypertensive control group. Leukotriene content in BALF and lung tissue obtained 2 h after delivery was not increased in the hypertensive group. TxB2, but not 6-keto-PGF1 alpha, content was higher in lung tissue from the hypertensive group (P less than 0.02). Thus lung leukotriene content did not decrease from fetal values after cesarean-section delivery, and the lipoxygenase pathway was not significantly activated with delivery after chronic intrauterine pulmonary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The Effect of Taxifolin on Cisplatin-Induced Pulmonary Damage in Rats: A Biochemical and Histopathological Evaluation

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Edhem Unver ◽  
Mustafa Tosun ◽  
Hasan Olmez ◽  
Mehmet Kuzucu ◽  
Ferda Keskin Cimen ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Oxidative Dna Damage ◽  
Control Group ◽  
Distilled Water ◽  
Tissue Samples ◽  
Experimental Procedure ◽  
Water As Solvent ◽  
Pulmonary Damage ◽  
Healthy Control ◽  
Histopathological Results

The effect of taxifolin on cisplatin-induced oxidative pulmonary damage was investigated biochemically and histopathologically in male albino Wistar rats. There were four groups, with six animals in each group: 50 mg/kg of taxifolin plus 2.5 mg/kg of cisplatin (TC) group, 2.5 mg/kg of cisplatin only (CIS) group, 50 mg/kg of taxifolin only (TG) group, and a healthy control group (HG). In terms of the experimental procedure, the animals in the TC and TG groups were first treated via oral gavage. The CIS and HG groups received distilled water as solvent, respectively. One hour later, the TC and CIS groups received cisplatin at a dose of 2.5 mg/kg (injected intraperitoneally). Taxifolin, cisplatin, and the distilled water were administered at the indicated dose and volume, using the same method daily for 14 d. At the end of this period, the animals were killed with a high dosage of thiopental anaesthesia (50 mg/kg). Blood and lung tissue samples were taken for biochemical (malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), and 8-hydroxy-2 deoxyguanosine (8-OHdG)) analyses and histopathological examinations. The biochemical and histopathological results in the TC and HG groups were then compared with those in the CIS group. Cisplatin increased the levels of MDA, myeloperoxidase, and 8-OHdG, a marker of oxidative DNA damage, and reduced the amount of tGSH in the lung tissue. Moreover, severe alveolar damage, including oedema and extensive alveolar septal fibrosis, in addition to infiltration of polymorphic nuclear leucocytes and haemorrhagic foci, was observed in the CIS group. These histopathological findings demonstrate that taxifolin provides protection against pulmonary oxidative stress by preventing increases in oxidant parameters and decreases in antioxidants.

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