scholarly journals PSVI-14 Differentially expressed microRNAs with potential regulatory roles in ileum of Holstein cows with subclinical Johne’s disease

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 206-207
Author(s):  
Mengqi Wang ◽  
Nathalie Bissonnette ◽  
Philip Griebel ◽  
Pier-Luc Dudemaine ◽  
Duy N Do ◽  
...  

Abstract Paratuberculosis or Johne’s disease (JD), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic inflammatory disorder of the intestinal tract of ruminants. The mechanisms of JD pathogenesis remain unclear but MAP can cause chronic inflammatory lesions in the terminal small intestine of cattle. Using microRNA (miRNA) transcriptome analysis, this study investigated the impact of MAP infection on miRNA expression and their potential regulatory roles in JD progression. Ileal tissues were collected from MAP infected Holstein cows (n = 5) and healthy cows (n = 5). Purified total RNA were used to construct libraries followed by next generation sequencing, bioinformatic processing using a standard pipeline, differential miRNA expression analysis with DESeq2 software, and functional enrichment with ClueGo app in Cytoscape. A total of 269 miRNAs were expressed in ileal tissue including three abundantly expressed miRNAs (Bta-miR-143; 54.05% of total read counts), bta-miR-145 (11.54%) and bta-miR-192 (4.31%)). Twenty miRNAs were significantly (P < 0.05) differently expressed (DE) when comparing ileal tissues from MAP infected and uninfected cows. Bta-miR-383 (fold change = -12.93) and bta-miR-1842 (fold-change = 8.17) were the most down- and up-regulated miRNAs, respectively. Amongst the DE miRNAs, bta-miR-146a, bta-miR-146b and bta-miR-393 are inflammation-related miRNAs and considered potential biomarkers of bovine mastitis and other diseases, while bta-miR-370 and bta-miR-383 are associated with lipid metabolism. The predicted target genes of DE miRNAs were enriched (P < 0.05) for gene ontology terms related to regulation of metabolic, cell and developmental processes, and immune system development. KEGG pathway analysis revealed potential involvement in immune regulation (e.g. T-cell receptor signaling and C-type lectin receptor signaling pathways) and pathways in cancer were also enriched (P < 0.05). Our results indicate that some DE miRNAs play important roles by regulating metabolism and immune processes during JD and provide DE miRNAs that might form targets for future development of intervention measures.

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 207-208
Author(s):  
Mengqi Wang ◽  
Nathalie Bissonnette ◽  
Philip Griebel ◽  
Pier-Luc Dudemaine ◽  
Duy N Do ◽  
...  

Abstract Johne’s disease (JD) is a chronic enteric disease of ruminants caused by Mycobacterium avium subsp. Paratuberculosis (MAP) but immune and metabolic mechanisms affecting JD progression have not been clearly elucidated. MicroRNAs (miRNA) have been reported to play important roles in numerous biological processes by regulating gene expression. In this study, miRNA expression in ileal lymph nodes (ILLN) from MAP positive (JD subclinical stage) Holstein cows (n = 5) and MAP negative cows (n = 5) were characterized by high throughput sequencing. MiRNA-sequence data was processed using a standard pipeline followed by functional enrichment with ClueGo app in Cytoscape. Among 324 expressed miRNAs, 37 were differently expressed (DE) (18 up-regulated and 19 down-regulated) in MAP infected cows relative to MAP negative cows. Bta-miR-100 (fold change = -2.29), a down-regulated miRNA, has previously been associated with Streptococcus uberis and MAP infections in cows, while bta-miR-330 (fold change = 63.42), the most up-regulated miRNA, was previously reported to be present in the sera of MAP infected calves. Predicted target genes of 37 DE miRNAs were enriched (P < 0.05) in gene ontology terms related to metabolic, cellular and developmental processes, and immune system development, as well as pathways related to cancer and Th17 cell differentiation, and lysosome compartmentalization. This suggests that miRNAs DE following MAP infection may be involved in regulating a wide variety of processes. In addition, 5 DE miRNAs were negatively correlated (P < 0.05) with 39 DE mRNAs (mRNAs expressed in the same tissue), comprising 42 negatively correlated DE miRNA-mRNA pairs. Bta-miR-2447 was negatively correlated with 29 DE mRNAs, suggesting it may be an important hub miRNA in the regulation of MAP infection in ILLN tissue. Our data thus suggest that bta-miR-100, bta-miR-330 and bta-miR-2447, which are implicated in the Th17 cell differentiation pathway, may be key regulators of the host response during MAP infection in ILLN.


2021 ◽  
Vol 12 ◽  
Author(s):  
Maryam Heidari ◽  
Abbas Pakdel ◽  
Mohammad Reza Bakhtiarizadeh ◽  
Fariba Dehghanian

Johne’s disease is a chronic infection of ruminants that burdens dairy herds with a significant economic loss. The pathogenesis of the disease has not been revealed clearly due to its complex nature. In order to achieve deeper biological insights into molecular mechanisms involved in MAP infection resulting in Johne’s disease, a system biology approach was used. As far as is known, this is the first study that considers lncRNAs, TFs, and mRNAs, simultaneously, to construct an integrated gene regulatory network involved in MAP infection. Weighted gene coexpression network analysis (WGCNA) and functional enrichment analysis were conducted to explore coexpression modules from which nonpreserved modules had altered connectivity patterns. After identification of hub and hub-hub genes as well as TFs and lncRNAs in the nonpreserved modules, integrated networks of lncRNA-mRNA-TF were constructed, and cis and trans targets of lncRNAs were identified. Both cis and trans targets of lncRNAs were found in eight nonpreserved modules. Twenty-one of 47 nonpreserved modules showed significant biological processes related to the immune system and MAP infection. Some of the MAP infection’s related pathways in the most important nonpreserved modules comprise “positive regulation of cytokine-mediated signaling pathway,” “negative regulation of leukocyte migration,” “T-cell differentiation,” “neutrophil activation,” and “defense response.” Furthermore, several genes were identified in these modules, including SLC11A1, MAPK8IP1, HMGCR, IFNGR1, CMPK2, CORO1A, IRF1, LDLR, BOLA-DMB, and BOLA-DMA, which are potentially associated with MAP pathogenesis. This study not only enhanced our knowledge of molecular mechanisms behind MAP infection but also highlighted several promising hub and hub-hub genes involved in macrophage-pathogen interaction.


2019 ◽  
Vol 185 (22) ◽  
pp. 693-693 ◽  
Author(s):  
Catalina Picasso-Risso ◽  
Ana Grau ◽  
Douwe Bakker ◽  
Jesus Nacar ◽  
Olga Mínguez ◽  
...  

BackgroundBovine tuberculosis (bTB) diagnosis is impaired by numerous factors including cross-reactivity with Mycobacterium avium subspecies paratuberculosis, which causes Johne’s disease (JD). In addition, the effect of repeated bTB-intradermal testing on the performance of JD diagnostic tests is not fully understood. This study aimed to evaluate the impact of repeated bTB-intradermal tests under field conditions in Spain on the JD serological status of cattle.MethodsbTB-positive herds (n=264) from Castilla-y-Leon region were selected and matched with officially tuberculosis-free control herds. The association between JD and bTB status at the herd level was assessed using conditional logistic regression and, in herds with both JD-positive and bTB-positive animals, a Bayesian hierarchical mixed-effect model was used for individual-level analysis.ResultsA significantly higher risk of being JD positive (OR: 1.48; 95 per cent CI: 1.01 to 2.15) was found for bTB-positive herds compared with controls. Individual results indicated that cattle tested more than three times per year, within the last 90 days and more than 12 months were more likely to be JD positive. A skin test-related boost in antibody response could be the cause of an apparent increase of the sensitivity of the JD-absorbed ELISA.ConclusionThe results demonstrate the interaction between bTB repeated testing and JD individual and herd-level results and this improved knowledge will facilitate the design of more effective control programmes in herds coinfected with two of the most important endemic diseases affecting cattle in Spain.


2001 ◽  
Vol 2001 ◽  
pp. 12-12
Author(s):  
M. J. Daniels ◽  
M. R. Hutchings ◽  
D. Henderson ◽  
A. Greig ◽  
K. Stevenson ◽  
...  

Paratuberculosis (Johne’s disease) is a chronic invariably fatal enteritis of cattle caused by the bacterium Mycobacterium avium subspecies paratuberculosis and has recently been isolated from wild rabbits. One potential route of transmission of M.a.paratuberculosis from rabbits to cattle is the ingestion of rabbit excreta contaminating pasture. Here we (1) determine the prevalence and level of infection in rabbits and their excreta (2) quantify the level of rabbit faeces contaminating cattle pastures and (3) determine the impact of rabbit faeces on cattle grazing behaviour.


2021 ◽  
Author(s):  
Susana I. S. Patuleia ◽  
Elsken van der Wall ◽  
Carla H. van Gils ◽  
Marije F. Bakker ◽  
Agnes Jager ◽  
...  

Abstract Purpose Investigation of nipple aspirate fluid (NAF)-based microRNAs (miRNAs) as a potential screening tool for women at increased risk of developing breast cancer is the scope of our research. While aiming to identify discriminating NAF-miRNAs between women with different mammographic densities, we were confronted with an unexpected confounder: NAF sample appearance. Here we report and alert for the impact of NAF color and cloudiness on miRNA assessment. Methods Seven classes of NAF colors coupled with cloudiness appearance were established. Using 173 NAF samples from 154 healthy women (19 samples were bilaterally collected), the expression of 14 target and 2 candidate endogenous control (EC) miRNAs was investigated using Taqman Advanced miRNA assays to identify significant differential expression patterns between color-cloudiness classes. Inter- and intra-individual variation of miRNA expression was analyzed using the coefficient of variation (CV). Results We found that between the seven NAF classes, fold change miRNA expression differences ranged between 2.4 and 19.6 depending on the interrogated miRNA. Clear NAF samples exhibited higher miRNA expression levels compared to cloudy NAF samples with fold change differences ranging between 1.1 and 6.2. Inter-individual and intra-individual miRNA expression was fairly stable (CV < 15 %), but nevertheless impacted by NAF sample appearance. Within NAF classes, inter-individual variation was largest for green samples (CV 6-15 %) and smallest for bloody samples (CV 2-6 %). Conclusions Our data indicate that NAF color and cloudiness influence miRNA expression and should, therefore, be systematically registered using an objective color classification system. Given that sample appearance is an inherent feature of NAF, these variables should be statistically controlled for in multivariate data analyses. This cautionary note and recommendations could be of value beyond the field of NAF-miRNAs, given that variability in sample color and cloudiness is likewise observed in liquid biopsies such as urine, cerebrospinal fluid and sputum, and could thereby influence the levels of miRNAs and other biomarkers.


2009 ◽  
Vol 92 (6) ◽  
pp. 2653-2661 ◽  
Author(s):  
R.L. Smith ◽  
Y.T. Grohn ◽  
A.K. Pradhan ◽  
R.H. Whitlock ◽  
J.S. Van Kessel ◽  
...  

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 20-21
Author(s):  
Eveline M Ibeagha-Awemu ◽  
Mengqi Wang ◽  
Nathalie Bissonnette ◽  
Philip Griebel ◽  
Pier-Luc Dudemaine ◽  
...  

Abstract Mycobacterium avium subsp. Paratuberculosis (MAP) is the causal agent of Johne’s disease (JD), a chronic intestinal disease affecting ruminants worldwide. This study investigated miRNA expression in jejunal intestine (JE) and jejunal lymph nodes (JELN), and the potential regulatory roles of miRNAs during JD progression. JE and JELN tissues were collected from 5 MAP positive (JD subclinical stage) Holstein cows and 5 MAP negative cows. Following miRNA sequencing, bioinformatic processing with a standard pipeline and functional analysis with ClueGo, 272 and 333 miRNAs were identified in JE and JELN, respectively. Compared with MAP negative cows, 13 and 71 miRNAs were differently expressed (DE) (P &lt; 0.05) in MAP infected JE and JELN, respectively. The most up-regulated and down-regulated miRNAs were bta-miR-485 (fold change = 6.18) and bta-miR-451 (fold change = -6.81), and bta-miR-331-5p (fold change = 35.56) and bta-miR-2285bk (fold change = -61.25) in JE and JELN, respectively. In JE, some DE miRNAs (miR-147 and miR-199a-5p) have been associated with glucose metabolism while several DE miRNAs in JELN have associations with immune response to disease (e.g. miR-146a and miR-146b have been associated with bovine mastitis and miR331-5p and miR-184 are important for human cancers). Target genes of JELN DE miRNAs were enriched (P &lt; 0.05) for more gene ontology terms (n = 180) and KEGG pathways (n = 123) as compared with JE (n = 90 and 25, respectively). Furthermore, JELN DE miRNAs were uniquely enriched in several immune related pathways including immune response regulating/activating signal transduction, T-cell/B-cell receptor signaling, Toll-like receptor signaling, TNF signaling pathways, etc., suggesting potential regulatory roles for JELN DE miRNAs in the host immune response to JD. In addition, interactions between DE miRNAs and DE mRNAs (expressed in the same samples) demonstrated important functions for miR-2284/2285 family members in JELN response to MAP infection. In conclusion, these results suggest site specific regulatory roles for miRNAs during MAP infection.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245836
Author(s):  
Myriam Klopfstein ◽  
Alexandra Leyer ◽  
Beat Berchtold ◽  
Paul Robert Torgerson ◽  
Mireille Meylan

Various measures have been advocated for the control of Johne’s disease (caused by Mycobacterium avium subsp. paratuberculosis, MAP) in different countries. Farmers’ compliance has been reported to be variable depending on disease prevalence and incentives to participate in control programs. After the prevalence of MAP shedding and risk factors for within-herd spread of MAP were assessed in 17 Swiss cattle herds (10 dairy and 7 beef), general and herd-specific recommendations were given to the farmers to reduce MAP transmission within the herd. Participation in the study and implementation of control measures were voluntary, no financial incentives were provided for the realization of control measures. After a 3-year period of monitored observation including biannual farm visits and discussion of the situation, the implementation of the recommended control measures and their effect on prevalence of MAP shedding were evaluated. Implementation of recommended general and farm-specific control measures was only partially realized. Neither the number of animals tested positive (before or during the study) nor the farmers’ knowledge about paratuberculosis were significantly associated with their compliance for the implementation of management changes. The apparent within-herd prevalence remained constant despite limited implementation of control measures, and no particular group of control measures was found to be associated with changes in prevalence. Farmers’ compliance for the implementation of control measures to reduce the impact of Johne’s disease in infected farms was very limited under Swiss farming conditions in the frame of voluntary participation in a research project. These results indicate that the losses associated with paratuberculosis in Swiss dairy and beef operations are not estimated to be high enough by the farmers to justify important efforts for control measures, and that incentives may be necessary to achieve efficient implementation of such measures.


2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic &#946;-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in &#946;-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of &#946;-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into &#946;-cells, resulting in enhanced &#946;-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of &#946;-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived &#946;-cells to therapeutically relevant outputs will be discussed as well.


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