scholarly journals Intestinal Transcriptomic and Histologic Profiling Reveals Tissue Repair Mechanisms Underlying Resistance to the Parasite Ceratonova shasta

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1179
Author(s):  
Damien E. Barrett ◽  
Itziar Estensoro ◽  
Ariadna Sitjà-Bobadilla ◽  
Jerri L. Bartholomew

Background: Myxozoan parasites infect fish worldwide causing significant disease or death in many economically important fish species, including rainbow trout and steelhead trout (Oncorhynchus mykiss). The myxozoan Ceratonova shasta is a parasite of salmon and trout that causes ceratomyxosis, a disease characterized by severe inflammation in the intestine resulting in hemorrhaging and necrosis. Populations of O. mykiss that are genetically fixed for resistance or susceptibility to ceratomyxosis exist naturally, offering a tractable system for studying the immune response to myxozoans. The aim of this study was to understand how steelhead trout that are resistant to the disease respond to C. shasta once it has become established in the intestine and identify potential mechanisms of resistance. Results: Sequencing of intestinal mRNA from resistant steelhead trout with severe C. shasta infections identified 417 genes differentially expressed during the initial stage of the infection compared to uninfected control fish. A strong induction of interferon-gamma and interferon-stimulated genes was evident, along with genes involved in cell adhesion and migration. A total of 11,984 genes were differentially expressed during the late stage of the infection, most notably interferon-gamma, interleukin-6, and immunoglobulin transcripts. A distinct hardening of the intestinal tissue and a strong inflammatory reaction in the intestinal submucosa including severe hyperplasia and inflammatory cell infiltrates were observed in response to the infection. The massive upregulation of caspase-14 early in the infection, a protein involved in keratinocyte differentiation might reflect the rapid onset of epithelial repair mechanisms, and the collagenous stratum compactum seemed to limit the spread of C. shasta within the intestinal layers. These observations could explain the ability of resistant fish to eventually recover from the infection. Conclusions: Our results suggest that resistance to ceratomyxosis involves both a rapid induction of key immune factors and a tissue response that limits the spread of the parasite and the subsequent tissue damage. These results improve our understanding of the myxozoan–host dialogue and provide a framework for future studies investigating the infection dynamics of C. shasta and other myxozoans.


2020 ◽  
Vol 26 (29) ◽  
pp. 3619-3630
Author(s):  
Saumya Choudhary ◽  
Dibyabhaba Pradhan ◽  
Noor S. Khan ◽  
Harpreet Singh ◽  
George Thomas ◽  
...  

Background: Psoriasis is a chronic immune mediated skin disorder with global prevalence of 0.2- 11.4%. Despite rare mortality, the severity of the disease could be understood by the accompanying comorbidities, that has even led to psychological problems among several patients. The cause and the disease mechanism still remain elusive. Objective: To identify potential therapeutic targets and affecting pathways for better insight of the disease pathogenesis. Method: The gene expression profile GSE13355 and GSE14905 were retrieved from NCBI, Gene Expression Omnibus database. The GEO profiles were integrated and the DEGs of lesional and non-lesional psoriasis skin were identified using the affy package in R software. The Kyoto Encyclopaedia of Genes and Genomes pathways of the DEGs were analyzed using clusterProfiler. Cytoscape, V3.7.1 was utilized to construct protein interaction network and analyze the interactome map of candidate proteins encoded in DEGs. Functionally relevant clusters were detected through Cytohubba and MCODE. Results: A total of 1013 genes were differentially expressed in lesional skin of which 557 were upregulated and 456 were downregulated. Seven dysregulated genes were extracted in non-lesional skin. The disease gene network of these DEGs revealed 75 newly identified differentially expressed gene that might have a role in development and progression of the disease. GO analysis revealed keratinocyte differentiation and positive regulation of cytokine production to be the most enriched biological process and molecular function. Cytokines -cytokine receptor was the most enriched pathways. Among 1013 identified DEGs in lesional group, 36 DEGs were found to have altered genetic signature including IL1B and STAT3 which are also reported as hub genes. CCNB1, CCNA2, CDK1, IL1B, CXCL8, MKI 67, ESR1, UBE2C, STAT1 and STAT3 were top 10 hub gene. Conclusion: The hub genes, genomic altered DEGs and other newly identified differentially dysregulated genes would improve our understanding of psoriasis pathogenesis, moreover, the hub genes could be explored as potential therapeutic targets for psoriasis.



2020 ◽  
Vol 21 (7) ◽  
pp. 2562 ◽  
Author(s):  
Charlotte Gibson ◽  
Marta de Ruijter-Villani ◽  
Stefan Bauersachs ◽  
Tom A.E. Stout

Preimplantation horse conceptuses require nutrients and signals from histotroph, the composition of which is regulated by luteal progesterone and conceptus-secreted factors. To distinguish progesterone and conceptus effects we shortened the period of endometrial progesterone-priming by asynchronous embryo transfer. Day 8 embryos were transferred to synchronous (day 8) or asynchronous (day 3) recipients, and RNA sequencing was performed on endometrium and conceptuses recovered 6 and 11 days later (embryo days 14 and 19). Asynchrony resulted in many more differentially expressed genes (DEGs) in conceptus membranes (3473) than endometrium (715). Gene ontology analysis identified upregulation in biological processes related to organogenesis and preventing apoptosis in synchronous conceptuses on day 14, and in cell adhesion and migration on day 19. Asynchrony also resulted in large numbers of DEGs related to ‘extracellular exosome’. In endometrium, genes involved in immunity, the inflammatory response, and apoptosis regulation were upregulated during synchronous pregnancy and, again, many genes related to extracellular exosome were differentially expressed. Interestingly, only 14 genes were differentially expressed in endometrium recovered 6 days after synchronous versus 11 days after asynchronous transfer (day 14 recipient in both). Among these, KNG1 and IGFBP3 were consistently upregulated in synchronous endometrium. Furthermore bradykinin, an active peptide cleaved from KNG1, stimulated prostaglandin release by cultured trophectoderm cells. The horse conceptus thus responds to a negatively asynchronous uterus by extensively adjusting its transcriptome, whereas the endometrial transcriptome is modified only subtly by a more advanced conceptus.



Vaccine ◽  
2003 ◽  
Vol 21 (11-12) ◽  
pp. 1158-1164 ◽  
Author(s):  
Amelia R Woolums ◽  
Leonardo Siger ◽  
Scott Johnson ◽  
Guillermo Gallo ◽  
Jennifer Conlon
Keyword(s):  


Author(s):  
Rashid Saif ◽  
Tania Mahmood ◽  
Aniqa Ejaz ◽  
Saeeda Zia

The Pashmina and Barbari are two famous goat breeds found in the wide areas of the Indo-Pak region. Pashmina is famous for its long hair-fiber (Cashmere) production while Barbari is not-selected for this trait. So, the mRNA expression profiling in the skin samples of both breeds would be an attractive and judicious approach for detecting putative genes involved in this valued trait. Here, we performed differential gene expression analysis on publicly available RNA-Seq data from both breeds. Out of 44,617,994 filtered reads of Pashmina and 55,995,999 of Barbari which are 76.48% and 73.69% mapped to the ARS1 reference transcriptome assembly respectively. A pairwise comparison of both breeds resulted in 47,159 normalized expressed transcripts while 8,414 transcripts are differentially expressed above the significant threshold. Among these, 4,788 are upregulated in Pashmina while 3,626 transcripts are upregulated in Barbari. Fifty-nine transcripts harbor 57 genes including 32 LOC genes and 24 are annotated genes which were selected on the basis of TMM counts > 500. Genes with ectopic expressions other than uncharacterized and LOC symbol genes are Keratins (KRT) and Keratin Associated Proteins (KRTAPs), CystatinA&6, TCHH, SPRR4, PPIA, SLC25A4, S100A11, DMKN, LOR, ANXA2, PRR9 and SFN. All of these genes are likely to be involved in keratinocyte differentiation, sulfur matrix proteins, dermal papilla cells, hair follicles proliferation, hair curvature, wool fiber diameter, hair transition, hair shaft differentiation and its keratinization. These differentially expressed reported genes are critically valuable for enhancing the quality and quantity of the pashmina fiber and overall breed improvement. This study will also provide important information on hair follicle differentiation for further enrichment analyses and introducing this valued trait to other goat breeds as well.



Author(s):  
Charlotte Gibson ◽  
Marta de Ruijter-Villani ◽  
Stefan Bauersachs ◽  
Tom A.E. Stout

Pre-implantation horse conceptuses require nutrients and signals from histotroph, the composition of which is regulated by luteal progesterone and conceptus-secreted factors. To distinguish progesterone and conceptus effects we shortened the period of endometrial progesterone-priming by asynchronous embryo transfer. Day 8 embryos were transferred to synchronous (day 8) or asynchronous (day 3) recipients, and RNA sequencing was performed on endometrium and conceptuses recovered 6 and 11 days later (embryo days 14 and 19). Asynchrony resulted in many more differentially expressed genes (DEGs) in conceptus membranes (3473) than endometrium (715). Gene ontology analysis identified upregulation in biological processes related to organogenesis and preventing apoptosis in synchronous conceptuses on day 14, and in cell adhesion and migration on day 19. Asynchrony also resulted in large numbers of DEGs related to ‘extracellular exosome’. In endometrium, genes involved in immunity, the inflammatory response, and apoptosis regulation were upregulated during synchronous pregnancy and, again, many genes related to extracellular exosome were differentially expressed. Interestingly, only 14 genes were differentially expressed in endometrium recovered 6 days after synchronous versus 11 days after asynchronous transfer (day 14 recipient in both). Among these, KNG1 and IGFBP3 were consistently up-regulated in synchronous endometrium. Furthermore bradykinin, an active peptide cleaved from KNG1, stimulated prostaglandin release by cultured trophectoderm cells. The horse conceptus thus responds to a negatively asynchronous uterus by extensively adjusting its transcriptome, whereas the endometrial transcriptome is modified only subtly by a more advanced conceptus.



2018 ◽  
Vol 26 (2) ◽  
pp. 179 ◽  
Author(s):  
Bohao Zhao ◽  
Yang Chen ◽  
Lin Mu ◽  
Shuaishuai Hu ◽  
Xinsheng Wu

Skin is an important trait for Rex rabbits and skin development is influenced by many processes, including hair follicle cycling, keratinocyte differentiation and formation of coat colour and skin morphogenesis. We identified differentially expressed microRNAs (miRNAs) between the back and belly skin in Rex rabbits. In total, 211 miRNAs (90 upregulated miRNAs and 121 downregulated miRNAs) were identified with a |log<sub>2</sub> (fold change)|&gt;1 and <em>P</em>-value&lt;0.05. Using target gene prediction for the miRNAs, differentially expressed predicted target genes were identified and the functional enrichment and signalling pathways of these target genes were processed to reveal their biological functions. A number of differentially expressed miRNAs were found to be involved in regulation of the cell cycle, skin epithelium differentiation, keratinocyte proliferation, hair follicle development and melanogenesis. In addition, target genes regulated by miRNAs play key roles in the activities of the Hedgehog signalling pathway, Wnt signalling pathway, Osteoclast differentiation and MAPK pathway, revealing mechanisms of skin development. Nine candidate miRNAs and 5 predicted target genes were selected for verification of their expression by quantitative reverse transcription polymerase chain reaction. A regulation network of miRNA and their target genes was constructed by analysing the GO enrichment and signalling pathways. Further studies should be carried out to validate the regulatory relationships between candidate miRNAs and their target genes.



2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Kezhu Li ◽  
Shu Guo ◽  
Shuang Tong ◽  
Qiang Sun ◽  
Shifeng Jin ◽  
...  

Background. Melanoma is the deadliest type of skin cancer. Until now, its pathological mechanisms, particularly the mechanism of metastasis, remain largely unknown. Our study on the identification of genes in association with metastasis for melanoma provides a novel understanding of melanoma. Methods. From the Gene Expression Omnibus (GEO) database, the gene expression microarray datasets GSE46517, GSE7553, and GSE8401 were downloaded. We made use of R aiming at analyzing the differentially expressed genes (DEGs) between metastatic and nonmetastatic melanoma. R was also used in differentially expressed miRNA (DEM) data mining from GSE18509, GSE19387, GSE24996, GSE34460, GSE35579, GSE36236, and GSE54492 datasets referring to Li’s study. Based on the DEG and DEM data, we performed functional enrichment analysis through the application of the DAVID database. Furthermore, we constructed the protein-protein interaction (PPI) network and established functional modules by making use of the STRING database. Through making use of Cytoscape, the PPI results were visualized. We predicted the targets of the DEMs through applying TargetScan, miRanda, and PITA databases and identified the overlapping genes between DEGs and predicted targets, followed by the construction of DEM-DEG pair network. The expressions of these keratinocyte differentiation-involved genes in Module 1 were identified based on the data from TCGA. Results. 239 DEGs were screened out in all 3 datasets, which were inclusive of 21 positively regulated genes and 218 negatively regulated genes. Based on these 239 DEGs, we finished constructing the PPI network which was formed from 225 nodes and 846 edges. We finished establishing 3 functional modules. And we analyzed 92 overlapping genes and 26 miRNA, including 11 upregulated genes targeted by 11 negatively regulated DEMs and 81 downregulated genes targeted by 15 positively regulated DEMs. As proof of the differential expression of metastasis-associated genes, eleven keratinocyte differentiation-involved genes, including LOR, EVPL, SPRR1A, FLG, SPRR1B, SPRR2B, TGM1, DSP, CSTA, CDSN, and IVL in Module 1, were obviously downregulated in metastatic melanoma tissue in comparison with primary melanoma tissue based on the data from TCGA. Conclusion. 239 melanoma metastasis-associated genes and 26 differentially expressed miRNA were identified in our study. The keratinocyte differentiation-involved genes may take part in melanoma metastasis, providing a latent molecular mechanism for this disease.



Author(s):  
R.F. Dodson ◽  
L.W-F Chu ◽  
N. Ishihara

The extent of damage surrounding an implanted electrode in the cerebral cortex is a question of significant importance with regard to attaining consistency and validity of physiological recordings. In order to determine the extent of such tissue changes, 150 micron diameter platinum electrodes were implanted in the cortex of four adult baboons, and after eight days the animals were sacrificed by whole body perfusion with a 3% glutaraldehyde in 0.1M phosphate fixative.The calvarium was carefully removed and the electrode tracts were readily discernible in the firm, glutaraldehyde fixed tissue.Careful dissection of the zone of the electrode tract resulted in a small block which was further sectioned into tip, mid-tract and surface areas. Ultrastructurally, damage extended from the electrode sheath to the greatest extent of from 0.2 to 3.5 mm.



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