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Article ; Online: MicroRNAs modulate immunological and inflammatory responses in Holstein cattle naturally infected with Mycobacterium avium subsp. paratuberculosis.

Badia-Bringué, Gerard / Canive, María / Blanco-Vázquez, Cristina / Torremocha, Rosana / Ovalle, Susana / Ramos-Ruiz, Ricardo / Casais, Rosa / Alonso-Hearn, Marta

Scientific reports

2024 Volume 14, Issue 1, Page(s) 173

Abstract: MicroRNAs (miRNAs) regulate the post-transcriptional expression of genes by binding to their target mRNAs. In this study, whole miRNA sequencing was used to compare the expression of miRNAs in ileocecal valve (ICV) and peripheral blood (PB) samples of ... ...

Abstract	MicroRNAs (miRNAs) regulate the post-transcriptional expression of genes by binding to their target mRNAs. In this study, whole miRNA sequencing was used to compare the expression of miRNAs in ileocecal valve (ICV) and peripheral blood (PB) samples of cows with focal or diffuse paratuberculosis (PTB)-associated lesions in gut tissues versus (vs) control cows without lesions. Among the eight miRNAs differentially expressed in the PB samples from cows with diffuse lesions vs controls, three (miR-19a, miR-144, miR32) were also down-regulated in cows with diffuse vs focal lesions. In the ICV samples, we identified a total of 4, 5, and 18 miRNAs differentially expressed in cows with focal lesions vs controls, diffuse lesions vs controls, and diffuse vs focal lesions, respectively. The differential expression of five microRNAs (miR-19a, miR-144, miR-2425-3p, miR-139, miR-101) was confirmed by RT-qPCR. Next, mRNA target prediction was performed for each differentially expressed miRNA. A functional analysis using the predicted gene targets revealed a significant enrichment of the RNA polymerase and MAPK signaling pathways in the comparison of cows with focal vs no lesions and with diffuse vs focal lesions, respectively. The identified miRNAs could be used for the development of novel diagnostic and therapeutical tools for PTB control.
MeSH term(s)	Female ; Cattle ; Animals ; Mycobacterium avium subsp. paratuberculosis ; MicroRNAs/genetics ; Paratuberculosis ; Ileocecal Valve
Chemical Substances	MicroRNAs
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-50251-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Bovine Intelectin 2 Expression as a Biomarker of Paratuberculosis Disease Progression

Blanco Vázquez, Cristina / Balseiro, Ana / Alonso-Hearn, Marta / Juste, Ramón A / Iglesias, Natalia / Canive, Maria / Casais, Rosa

Animals. 2021 May 12, v. 11, no. 5

2021

Abstract: Paratuberculosis (PTB), a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), is responsible for important economic losses in the dairy industry. Our previous RNA-sequencing (RNA-Seq) analysis showed that bovine ... ...

Abstract	Paratuberculosis (PTB), a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), is responsible for important economic losses in the dairy industry. Our previous RNA-sequencing (RNA-Seq) analysis showed that bovine intelectin 2 (ITLN2) precursor gene was overexpressed in ileocecal valve (ICV) samples of animals with focal (log2 fold-change = 10.6) and diffuse (log2 fold-change = 6.8) PTB-associated lesions compared to animals without lesions. This study analyzes the potential use of ITLN2, a protein that has been described as fundamental in the innate immune response to infections, as a biomarker of MAP infection. The presence of ITLN2 was investigated by quantitative immunohistochemical analysis of ICV samples of 20 Holstein Friesian cows showing focal (n = 5), multifocal (n = 5), diffuse (n = 5) and no histological lesions (n = 5). Significant differences were observed in the mean number of ITLN2 immunostained goblet and Paneth cells between the three histopathological types and the control. The number of immunolabelled cells was higher in the focal histopathological type (116.9 ± 113.9) followed by the multifocal (108.7 ± 140.5), diffuse (76.5 ± 97.8) and control types (41.0 ± 81.3). These results validate ITLN2 as a post-mortem biomarker of disease progression.
Keywords	Holstein ; Mycobacterium avium subsp. paratuberculosis ; biomarkers ; dairy industry ; disease progression ; enteritis ; genes ; histopathology ; immunohistochemistry ; innate immunity ; paratuberculosis ; sequence analysis
Language	English
Dates of publication	2021-0512
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-AP-2-clean
ISSN	2076-2615
DOI	10.3390/ani11051370
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Proteomic Serum Profiling of Holstein Friesian Cows with Different Pathological Forms of Bovine Paratuberculosis Reveals Changes in the Acute-Phase Response and Lipid Metabolism.

Navarro León, Alejandra Isabel / Muñoz, Marta / Iglesias, Natalia / Blanco-Vázquez, Cristina / Balseiro, Ana / Milhano Santos, Fátima / Ciordia, Sergio / Corrales, Fernando J / Iglesias, Tania / Casais, Rosa

Journal of proteome research

2023

Abstract: The lack of sensitive diagnostic methods to ... ...

Abstract	The lack of sensitive diagnostic methods to detect
Language	English
Publishing date	2023-10-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.3c00244
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Article: Bovine Intelectin 2 Expression as a Biomarker of Paratuberculosis Disease Progression.

Blanco Vázquez, Cristina / Balseiro, Ana / Alonso-Hearn, Marta / Juste, Ramón A / Iglesias, Natalia / Canive, Maria / Casais, Rosa

Animals : an open access journal from MDPI

2021 Volume 11, Issue 5

Abstract: Paratuberculosis (PTB), a chronic granulomatous enteritis caused ... ...

Abstract	Paratuberculosis (PTB), a chronic granulomatous enteritis caused by
Language	English
Publishing date	2021-05-12
Publishing country	Switzerland
Document type	Journal Article
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani11051370
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Summary-data based Mendelian randomization identifies gene expression regulatory polymorphisms associated with bovine paratuberculosis by modulation of the nuclear factor Kappa β (NF-κß)-mediated inflammatory response.

Badia-Bringué, Gerard / Canive, Maria / Fernandez-Jimenez, Nora / Lavín, José Luis / Casais, Rosa / Blanco-Vázquez, Cristina / Vázquez, Patricia / Fernández, Almudena / Bilbao, Jose Ramón / Garrido, Joseba M / Juste, Ramón A / González-Recio, Oscar / Alonso-Hearn, Marta

BMC genomics

2023 Volume 24, Issue 1, Page(s) 605

Abstract: Genome-wide association studies (GWAS) have identified host genetic variants associated with paratuberculosis (PTB) susceptibility. Most of the GWAS-identified SNPs are in non-coding regions. Connecting these non-coding variants and downstream affected ... ...

Abstract	Genome-wide association studies (GWAS) have identified host genetic variants associated with paratuberculosis (PTB) susceptibility. Most of the GWAS-identified SNPs are in non-coding regions. Connecting these non-coding variants and downstream affected genes is a challenge and, up to date, only a few functional mutations or expression quantitative loci (cis-eQTLs) associated with PTB susceptibility have been identified. In the current study, the associations between imputed whole-genome sequence genotypes and whole RNA-Sequencing data from peripheral blood (PB) and ileocecal valve (ICV) samples of Spanish Holstein cows (N = 16) were analyzed with TensorQTL. This approach allowed the identification of 88 and 37 cis-eQTLs regulating the expression levels of 90 and 37 genes in PB and ICV samples, respectively (False discorey rate, FDR ≤ 0.05). Next, we applied summary-based data Mendelian randomization (SMR) to integrate the cis-eQTL dataset with GWAS data obtained from a cohort of 813 culled cattle that were classified according to the presence or absence of PTB-associated histopathological lesions in gut tissues. After multiple testing corrections (FDR ≤ 0.05), we identified two novel cis-eQTLs affecting the expression of the early growth response factor 4 (EGR4) and the bovine neuroblastoma breakpoint family member 6-like protein isoform 2 (MGC134040) that showed pleiotropic associations with the presence of multifocal and diffuse lesions in gut tissues; P = 0.002 and P = 0.017, respectively. While EGR4 acts as a brake on T-cell proliferation and cytokine production through interaction with the nuclear factor Kappa β (NF-κß), MGC134040 is a target gene of NF-κß. Our findings provide a better understanding of the genetic factors influencing PTB outcomes, confirm that the multifocal lesions are localized/confined lesions that have different underlying host genetics than the diffuse lesions, and highlight regulatory SNPs and regulated-gene targets to design future functional studies.
MeSH term(s)	Humans ; Female ; Cattle ; Animals ; Paratuberculosis/genetics ; Genome-Wide Association Study/veterinary ; Mendelian Randomization Analysis ; Quantitative Trait Loci ; Gene Expression ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Early Growth Response Transcription Factors/genetics
Chemical Substances	EGR4 protein, human ; Early Growth Response Transcription Factors
Language	English
Publishing date	2023-10-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2041499-7
ISSN	1471-2164 ; 1471-2164
ISSN (online)	1471-2164
ISSN	1471-2164
DOI	10.1186/s12864-023-09710-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Efficacy of heat-inactivated

Juste, Ramón A / Blanco-Vázquez, Cristina / Barral, Marta / Prieto, José Miguel / Varela-Castro, Lucía / Lesellier, Sandrine / Dave, Dipesh / Sevilla, Iker A / Martín Ezquerra, Ana Belén / Adriaensen, Hans / Herrero-García, Gloria / Garrido, Joseba M / Casais, Rosa / Balseiro, Ana

Heliyon

2023 Volume 9, Issue 9, Page(s) e19349

Abstract: Badgers ( ...

Abstract	Badgers (
Language	English
Publishing date	2023-08-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e19349
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Article: Use of ATP-Binding Cassette Subfamily A Member 13 (ABCA13) for Sensitive Detection of Focal Pathological Forms of Subclinical Bovine Paratuberculosis.

Blanco-Vázquez, Cristina / Alonso-Hearn, Marta / Iglesias, Natalia / Vázquez, Patricia / Juste, Ramón A / Garrido, Joseba M / Balseiro, Ana / Canive, María / Amado, Javier / Queipo, Manuel A / Iglesias, Tania / Casais, Rosa

Frontiers in veterinary science

2022 Volume 9, Page(s) 816135

Abstract: Bovine paratuberculosis (PTB) is a chronic enteritis caused ... ...

Abstract	Bovine paratuberculosis (PTB) is a chronic enteritis caused by
Language	English
Publishing date	2022-03-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2022.816135
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Article: Evaluation of a droplet digital PCR assay for quantification of

Badia-Bringué, Gerard / Canive, Maria / Casais, Rosa / Blanco-Vázquez, Cristina / Amado, Javier / Iglesias, Natalia / González, Aitor / Bascones, Mertxe / Juste, Ramon A / Alonso-Hearn, Marta

Frontiers in veterinary science

2022 Volume 9, Page(s) 944189

Abstract: Bovine paratuberculosis (PTB) is an infectious disease that affects ruminants worldwide and is a burden on the dairy industry. PTB control measures include culling ... ...

Abstract	Bovine paratuberculosis (PTB) is an infectious disease that affects ruminants worldwide and is a burden on the dairy industry. PTB control measures include culling of
Language	English
Publishing date	2022-09-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2022.944189
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Correlations between single nucleotide polymorphisms in bovine

Canive, Maria / Casais, Rosa / Jimenez, Jose A / Blanco-Vazquez, Cristina / Amado, Javier / Garrido, Joseba M / Juste, Ramon A / Alonso-Hearn, Marta

Heliyon

2020 Volume 6, Issue 6, Page(s) e04254

Abstract: Little is known about the correlations between the genetic susceptibility/resistance ... ...

Abstract	Little is known about the correlations between the genetic susceptibility/resistance to
Language	English
Publishing date	2020-06-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2020.e04254
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Correlations between single nucleotide polymorphisms in bovine CD209, SLC11A1, SP110 and TLR2 genes and estimated breeding values for several traits in Spanish Holstein cattle

Canive, Maria / Casais, Rosa / Jimenez, Jose A / Blanco-Vazquez, Cristina / Amado, Javier / Garrido, Joseba M / Juste, Ramon A / Alonso-Hearn, Marta

Heliyon. 2020 June, v. 6, no. 6

2020

Abstract: Little is known about the correlations between the genetic susceptibility/resistance to Mycobacterium avium subsp. paratuberculosis (Map) infection and the estimated breeding values for type, production and functional traits. Previously, we identified 70 ...

Abstract	Little is known about the correlations between the genetic susceptibility/resistance to Mycobacterium avium subsp. paratuberculosis (Map) infection and the estimated breeding values for type, production and functional traits. Previously, we identified 70 combinations of five single nucleotide polymorphisms (SNPs) in four bovine innate immune genes (SLC11A1, SP110, TLR2, CD209) that are associated with the genetic risk of paratuberculosis (PTB) or Johne's disease progression, which can be graded as low (LOWIN), latent (LATIN), or patent (PATIN) risk. Other possible combinations of these 5 SNPs were grouped in the average group (AVERIN). In the current study, differences in estimated breeding values (EBVs) for several traits were analyzed using linear models in a large cohort of Holstein cows (N = 15656) genotyped across Spain in 2016 or 2017. After the assignment of each genotyped cow to a risk group, cows within the PATIN risk group (N = 1448) had a superior combined genetic index (2797.57), type genetic index (524.62), milk yield (653.92 kg), protein yield (21.77 kg), fat yield (24.82 kg) and economic merit index (125 Euros) compared with the other three risk groups. Statistically significant differences in the longevity scores between the cows that were included in the PATIN risk group (108.85) and the LOWIN (107.82) and AVERIN (107.92) groups were also observed. The associations between the genetic risk groups and PTB diagnostic results were validated in a population of 99 cows from a Spanish farm with a high prevalence of PTB. Significant differences in ELISA readings between the PATIN (65.49 %) and the AVERIN (15.97 %), LATIN (2.11 %), and LOWIN (3.27 %) groups were observed. In addition, significant differences in Map DNA copies/gram of feces were observed between the PATIN and the other three risk groups. These results together with the substantial economic impact of PTB in dairy cattle support the selection of the animals with less susceptibility to PTB in the Spanish breeding program.
Keywords	DNA ; Holstein ; Mycobacterium avium subsp. paratuberculosis ; cows ; dairy cattle ; disease progression ; economic impact ; farms ; feces ; genotyping ; longevity ; milk yield ; paratuberculosis ; risk ; Spain
Language	English
Dates of publication	2020-06
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2020.e04254
Database	NAL-Catalogue (AGRICOLA)

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