BACKGROUND

The variation in cystic fibrosis (CF) lung disease not always is explained by the CFTR genotype, so it has become apparent that modifier genes must play a considerable role in the phenotypic heterogeneity of CF, so we investigated the association of allelic variants in modifier genes that modulate the severity of lung function in a group of Mexican patients diagnosed with CF.

METHODS

We included 140 CF patients classified according to lung phenotype and analyzed 17 single nucleotide polymorphisms (SNPs) by TaqMan® allelic discrimination.

RESULTS

We demonstrated that patients with GG or GC genotype of the allelic variant rs11003125 (MBL2-550) of the MBL2 gene exhibit most of the lung manifestations at an earlier age; and the rs1042713 allelic variant of ADRB2 gene, showed statistical difference only with the age of first spirometry. When we used the dominant model, the MBL2 allele rs11003125 (MBL2-550; p = 0.022, Odds Ratio (OR) 2.87, 95% CI 1.14-7.27) was significantly associated with CF patients as risk factor, and the ADRB2 allele rs1042713 (p.Arg16Gly; p = 0.005, Odds Ratio (OR) 0.37, 95% CI 0.19-0.75) was significantly associated with CF patients as protect factor.

CONCLUSIONS

Our findings suggest that the MBL2 and ADRB2 genes exerts an important genetic influence on the lung disease in our patients. Taking into account our results, we insist on not leaving aside this type of studies, since having techniques such as GWAS or WES will be able to advance in achieving a better quality of life for CF patients with severe lung disease.

The association between MBL2 gene polymorphisms and the risk of asthma has been evaluated in multiple studies; however, the results are inconsistent.

To perform a meta-analysis to explore whether MBL2 gene polymorphisms were associated with the risk of asthma.

We searched PubMed, Web of Science, and Cochrane Library to find relevant articles published up to March 2016. Nine studies, including 2066 cases and 2183 controls, were included in the meta-analysis. The strength of association was evaluated by odds ratio (OR) with 95% confidence interval (CI).

The results reveal that MBL2 gene polymorphisms (codon 54 A/B, -550 H/L or -221 X/Y) were not associated with the risk of asthma (codon 54 A/B: BB+AB vs AA: OR, 1.02; 95% CI, 0.85-1.23; -550 H/L: LL+HL vs HH: OR, 0.81; 95% CI, 0.63-1.03; -221 X/Y: XX+YX vs YY: OR, 0.85; 95% CI, 0.69-1.04). Subgroup analysis by ethnicity implied that the MBL2 codon 54 A/B polymorphism was not significantly associated with the risk of asthma in Asians (BB+AB vs AA: OR, 0.95; 95% CI, 0.70-1.29) or whites (BB+AB vs AA: OR, 1.07; 95% CI, 0.84-1.35).

The results indicated that MBL2 gene polymorphisms (codon 54 A/B, -550 H/L or -221 X/Y) may be not associated with the risk of asthma.

Chronic infection with Hepacivirus C (HCV) can lead to the occurrence of antinuclear antibodies (ANAs) and changes in cytokine profiles that can be similar to autoimmune diseases. The aim of the study was to identify polymorphisms in important mediators of the immune response in association with ANAs, which could contribute to the development of autoimmunity in hepatitis C. The study included 87 patients with chronic hepatitis C who were evaluated for the presence of ANA (indirect immunofluorescence) and for polymorphisms in the FOXP3, IFNG, IL6, IL8, IL10, MBL2, CRP, TGFΒ1 and TNFA genes (real-time PCR). Of the patients evaluated, 17 (19.54%) had ANA reactivity. The G allele of the FOXP3 rs2232365 polymorphism was more frequent in ANA-positive women (p = 0.0231; OR = 3,285). The C allele of the TGFΒ1 rs1800469 polymorphism was associated with ANA production (p = 0.0169; OR = 2.88). The results suggest that polymorphisms in genes related to immunological regulation may be associated with mechanisms that lead to the emergence of autoantibodies in the context of chronic Hepacivirus C infection.

Keywords: Ana; Chronic hepatitis C; FOXP3; Immune response; Immunology; Infectious disease; Microbiology; Polymorphisms; TGF-β1; Virology; Viruses.

The objective of this study was to test for association of candidate single nucleotide polymorphisms (SNPs) with sow prolificacy reproductive traits, such as litter size, ovulation rate and lifetime performance, in gilts of a Large White pig population. Preliminary research on 25 animals selected from the high- and low-performance groups of 347 animals with case-control studies indicated that seven genes were associated with total number of piglets born (TNB). Six of the seven genes were associated with reproductive traits, including TNB, number of piglets born alive (NBA) and average weight of piglet weaning (AWW). A MBL2 SNP was significantly associated with TNB and NBA in first parity. A CFB SNP was associated with TNB in first parity. An ACE SNP was associated with TNB in first and second parities. An EGF polymorphism was associated with TNB, NBA and AWW in second parity. A KCNC2 polymorphism was significantly associated with TNB and NBA in second parity. A SLC22A5 SNP was associated with TNB and NBA in second parity. Six candidate SNPs were associated with TNB; the only exception was a PRKAG3 polymorphism. A candidate gene approach enables some of these polymorphisms to be used in genetic improvement programs based on marker-assisted selection.

Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Mannose-binding lectin (MBL) is an acute phase protein associated with the pathophysiology of leprosy. Some studies have shown that there is a correlation between serum levels of MBL and polymorphisms in its gene associated with susceptibility per se and to different clinical forms. The aim of this study was to conduct a systematic review of publications in the literature that studied the association of MBL with leprosy. Databases were searched until December 2020 (PROSPERO: CRD42020158458), and additional searches were conducted scanning the reference lists of the articles. Two independent reviewers assessed the study quality using the Newcastle-Ottawa Quality Assessment Scale. Finally, 10 eligible articles were included in the study. The overall results indicated that both low MBL serum levels and polymorphisms in the structural or promoter region of its gene seem to be associated as protective factors against the development of severe forms. The results suggest that MBL may play a role in the clinical progression of leprosy.

Keywords: Complement system; Innate immunity; Leprosy; MBL2; Polymorphism.

H. pylori is considered to be a major etiological agent of chronic gastritis. Mannan-binding lectin (MBL) is one of the key factors of the innate immunity. It belongs to collectins binding to saccharides on the surface of a variety of pathogenic microorganisms, H. pylori including. MBL after coating the bacteria is recognized by the receptor on macrophages, facilitates phagocytosis by direct opsonization and activates complement via the lectin pathway which protects the host against infection. Single nucleotide polymorphisms of MBL2 gene affect both MBL concentration and biological activity.

OBJECTIVE

Evaluation of the correlation between the occurrence of MBL2 gene mutations, MBL concentration in serum, and prevalence of duodenal ulcer and chronic gastritis with or without H. pylori infection.

METHODS

The study comprised 174 children aged 6-17 years (mean 13.1 x 4.2), among them 74 children with H. pylori infection-associated chronic gastritis (group Hp+), 41 with H. pylori infection excluded (group Hp-), and 11 children with duodenal ulcer (DU). The control group consisted of 46 healthy children without gastritis, endoscopically checked. Determination of serum MBL concentration was performed using ELISA. Polymorphisms of the promoter region as well as mutations of exon 1 MBL2 gene were identified with polymerase chain reaction methods. H. pylori was detected with both urease test and histopathology Giemsa staining.

RESULTS

MBL serum concentration was significantly lower in children with both Hp+ (1809 ng/ml) and Hp-gastritis (1439 ng/ml) when compared to the control group (2545 ng/ml) (p < 0.05 and p < 0.01, respectively). The same trend (however the difference was insignificant) was observed in the case of DU group (1643 ng/ml). The frequency of MBL2 gene mutations did not differ between any group of patients as compared to controls.

CONCLUSIONS

No influence of MBL2 genotype on the incidence of duodenal ulcer or gastritis was found. MBL serum concentrations are lower in chronic gastritis patients (with or without H. pylori infection) when compared to the age-matched healthy individuals.

OBJECTIVE

Bone mineral density (BMD) is under strong genetic regulation, but it is not clear which genes are involved in the regulation, particularly in Asian populations. This study sought to determine the association between 29 genes discovered by Caucasian-based genome-wide association studies and BMD in a Vietnamese population.

METHODS

The study involved 564 Vietnamese men and women aged 18 years and over (average age: 47 years) who were randomly sampled from the Ho Chi Minh City. BMD at the femoral neck, lumbar spine, total hip and whole body was measured by DXA (Hologic QDR4500, Bedford, MA, USA). Thirty-two single nucleotide polymorphisms (SNPs) in 29 genes were genotyped using Sequenom MassARRAY technology. The magnitude of association between SNPs and BMD was analyzed by the linear regression model. The Bayesian model average method was used to identify SNPs that are independently associated with BMD.

RESULTS

The distribution of genotypes of all, but two, SNPs was consistent with the Hardy-Weinberg equilibrium law. After adjusting for age, gender and weight, 3 SNPs were associated with BMD: rs2016266 (SP7 gene), rs7543680 (ZBTB40 gene), and rs1373004 (MBL2/DKK1 gene). Among the three genetic variants, the SNP rs2016266 had the strongest association, with each minor allele being associated with ~0.02 g/cm(2) increase in BMD at the femoral neck and whole body. Each of these genetic variant explained about 0.2 to 1.1% variance of BMD. All other SNPs were not significantly associated with BMD.

CONCLUSIONS

These results suggest that genetic variants in the SP7, ZBTB40 and MBL2/DKK1 genes are associated with BMD in the Vietnamese population, and that the effect of these genes on BMD is likely to be modest.

Turner syndrome (TS) is characterized by a set of clinical conditions, including autoimmune/inflammatory diseases and infectious conditions, that can compromise a patient's quality of life. Here we assessed polymorphisms in CTLA-4 +49A/G (rs231775), PTPN22 +1858G/A (rs2476601), and MBL2 -550 (H/L) (rs11003125), -221(X/Y) (rs7096206) and exon 1 (A/O) in women from northeastern Brazil to determine whether polymorphisms within these key immune response genes confer differential susceptibility to clinical conditions in TS. A case-control genetic association study was performed, including 86 female TS patients and 179 healthy women. An association was observed for the A/G genotype of CTLA-4 +49A/G in TS patients (p=0.043, odds ratio [OR]=0.54). In addition, an association between the CTLA-4 G/G genotype and obesity was detected in TS patients (p=0.02, OR=6.04). Regarding, the -550(H/L) polymorphism in the MBL2 promoter, the frequency of the H/L genotype was significantly higher in the TS group than healthy controls (p=0.01, OR=1.96). The H/H genotype indicated a protective effect in TS patients (p=0.01, OR=0.23). No differences were observed in the distribution of -221(X/Y), MBL2 exon 1 variants, and PTPN22 +1858G/A in any assessed groups. CTLA-4 variants are potentially involved in obesity in this cohort of TS patients from northeastern Brazil.

OBJECTIVE

To assess the association of the G54D (rs1800450) polymorphism of the gene MBL2 in the gestational diabetes mellitus with the need for additional treatment and the occurrence of large newborns for the gestational age.

METHODS

One hundred and five patients recruited in Joinville--Brazil were evaluated between November 2010 and October 2012. Pregnant women were divided in two groups correspondents to the presence (n = 37) or absence (n = 68) of the mutant allele. The variants of the polymorphism G54D were identified by restriction fragment lengths polymorphisms (RFLP). Anthropometric and biochemical parameters of the mother and the newborn, and the necessity of additional therapy associated with diet were assessed as the primary outcomes.

RESULTS

Thirty-five point two percent of the evaluated patients carried at least one mutated allele of G54D polymorphism. There were no significant differences in weight gain, parity, age, body mass index and gestational age of arrival at maternity between the two groups. The groups of patients with or without the mutated allele did not differ in the need for additional treatment associated with diet (16.2% vs. 26.7%) respectively and with the occurrence of large newborns for gestational age (24.3% vs. 13.2%).

CONCLUSIONS

Our data showed that the polymorphism G54D of the gene MBL2 had no effect in the need for additional treatment associated with the diet-based therapy and in the occurrence of large newborns for gestational age in the studied population.

BACKGROUND

Meningococcal disease is a leading cause of death due to infection in children. Differences in susceptibility and disease progression between children are unknown. The complement system plays a key role in the innate immunity against N. meningitides and could explain that differences in the response of individuals. The aim of this study was to evaluate the occurrence of complement system deficiencies and MBL2 polymorphism in patients with previous meningococcal disease.

METHODS

We evaluated 40 children with confirmed previous diagnosis of any form of meningococcal disease and performed quantification analysis of the complement system; C3, C4, and CH50, as well the analysis of the polymorphism of the MBL2 gene.

RESULTS

The major deficiency was found for C4 (27.5%) followed by C3 and CH50 (2.5%). Genotyping of MBL2 showed 21 cases of homozygous wild type allele named AA, (55.3%), 14 cases heterozygous, AO (36.8%), and 3 homozygous variant alleles, OO, (7.9%).

CONCLUSIONS

Complement deficiency and polymorphism in the MBL2 gene are possible explanations for the development of meningococcal disease in some patients. Evaluation of complement could be suggested for individuals affected by this serious disease.

OBJECTIVE

Mannose-binding lectin and macrophage migration inhibitory factor gene polymorphisms are associated with several acute/chronic autoimmune or inflammatory diseases. The aim of this study was to investigate if there was any association between mannose-binding lectin 2 (MBL2) and macrophage migration inhibitory factor (MIF) gene polymorphisms and profound congenital sensorineural hearing loss in children who underwent cochlear implantation.

METHODS

A total of 62 patients with congenital hearing loss and 80 age- and sex-matched healthy controls were evaluated for codon 54 A/B polymorphisms in MBL2 and the-173 G/C polymorphism in MIF by using the polymerase chain reaction and restriction fragment length polymorphism method.

RESULTS

The frequency of the BB genotype of MBL2 and MIF -173 GC genotype were statistically significantly higher in the patient group than in the controls (p=0.0127, p=0.0408, respectively).

CONCLUSIONS

In this study, we found that a subject who is homozygous for the variant allele B of codon 54 of the MBL2and heterozygous for variant allele C of -173 MIF has a risk factor for sensorineural hearing loss.

Introduction: This study aimed to determine the association between serum mannose-binding lectin (MBL) levels, gene polymorphisms and late-onset sepsis (LOS) in preterm infants. Methods: Infants with <37 gestational weeks were categorized into two groups according to the presence of LOS during their hospitalization. An MBL level <700 ng/ml was defined as deficiency, <400 ng/ml as severe deficiency. Codon 54 and 57 polymorphisms of MBL2 gene were analyzed. Results: Overall, 153 preterm infants were included. MBL deficiency was found to be more common in the LOS group (p = 0.02). The rate of Gram-negative sepsis was higher in MBL2 variant-type (p = 0.01). In the logistic regression analysis, MBL levels <700 ng/ml were found to have a significant effect on LOS development (odds ratio: 2.692, 95% confidence interval 1.196-5.8, p = 0.02). Conclusions: MBL deficiency is an important risk factor for the development of LOS. Furthermore, there is an association between MBL2 gene polymorphism and Gram-negative sepsis.

Chagas disease (CD), caused by infection with the parasite Trypanosoma cruzi, leads to severe cardiomyopathy in 20-30% of patients, whereas the remainder may stay asymptomatic and never develop cardiomyopathy or other clinical manifestations. The underlying cause for this variable outcome is not fully characterized, although previous studies have found high levels of circulating mannose-binding lectin (MBL) to be associated with cardiac failure echocardiographic changes. We report three indeterminate (asymptomatic) chronic Chagas patients who were followed up for 10 years. Two of these patients developed chronic chagasic cardiomyopathy (CCC) during this follow-up period and, when genotyped, were found to be carriers of the high MBL producer HYPA/HYPA genotype, suggesting that genetically determined high MBL serum might be associated with the risk of CCC development. These results suggest the use of MBL quantification and MBL2 genotyping as tools for clinical assessment in patients with chronic CD.

Background: Multiple myeloma (MM) is a malignant disease manifested by the clonal proliferation of atypical plasma cells. Macrophage inhibitory factor (MIF) is one of the pleiotropic regulators in various biological and cellular processes. Mannose-binding lectin (MBL) is a crucial protein involved in the lectin pathway of the immune system.

Objective: We aimed to assess whether variants of MIF and MBL2 genes are associated with MM among a Turkish population.

Methods: We analyzed the MIF-173G/C (rs755622) and MBL2 codon 54A/B (rs1800450) variants in 200 patients with MM and 200 healthy control subjects using a polymerase chain reaction (PCR) followed by restriction endonuclease digestion. There was also an evaluation of the patients undergoing autologous stem-cell transplantation (ASCT) for these variants.

Results: AA and BB genotypes of MBL2 codon 54A/B increased in the patients as compared to the controls (p=0.008, p=0.001, respectively). The subjects carrying AA and BB genotypes of MBL2 were at high risk of development of susceptibility to MM by 7.377 and 8.812 times, respectively. The distribution of MBL2 codon 54A/B alleles was similar between the groups (p>0 .05). There was no statistical difference between the patients and controls in the genotype and allele frequencies of the MIF-173G/C variant (p>0 .05). The patients undergoing ASCT, MBL2 codon54A/B AA and BB genotypes also showed association with increased risk for MM (p=0.004, p=0.001, respectively).

Conclusion: As far as we know, this is the first report of the study on an association between these variants and MM in our population. Our results indicate that the MBL2 codon 54A/B variant may be associated with susceptibility to MM.</p>.

Keywords: Multiple myeloma; Turkishpopulation; macrophage inhibitory factor; malignant disease; mannose binding lectin; variant.

Vitamin A (VA) deficiency remains prevalent in resource limited areas. Using Citrobacter rodentium infection in mice as a model for diarrheal diseases, previous reports showed reduced pathogen clearance and survival due to vitamin A deficient (VAD) status. To characterize the impact of preexisting VA deficiency on gene expression patterns in the intestines, and to discover novel target genes in VA-related biological pathways, VA deficiency in mice were induced by diet. Total mRNAs were extracted from small intestine (SI) and colon, and sequenced. Differentially Expressed Gene (DEG), Gene Ontology (GO) enrichment, and co-expression network analyses were performed. DEGs compared between VAS and VAD groups detected 49 SI and 94 colon genes. By GO information, SI DEGs were significantly enriched in categories relevant to retinoid metabolic process, molecule binding, and immune function. Three co-expression modules showed significant correlation with VA status in SI; these modules contained four known retinoic acid targets. In addition, other SI genes of interest (e.g., Mbl2, Cxcl14, and Nr0b2) in these modules were suggested as new candidate genes regulated by VA. Furthermore, our analysis showed that markers of two cell types in SI, mast cells and Tuft cells, were significantly altered by VA status. In colon, "cell division" was the only enriched category and was negatively associated with VA. Thus, these data suggested that SI and colon have distinct networks under the regulation of dietary VA, and that preexisting VA deficiency could have a significant impact on the host response to a variety of disease conditions.

Keywords: RNAseq; Weighted Gene Co-expression Network Analysis (WGCNA); colon; gene expression profile; small intestine; vitamin A deficiency.

A 20-kDa ribonuclease (RNase) was purified from fresh fruiting bodies of cultured Schizophyllum commune mushrooms. The RNase was not adsorbed on Affi-gel blue gel but adsorbed on DEAE-cellulose and CM-cellulose. It exhibited maximal RNase activity at pH 6.0 and 70°C. It demonstrated the highest ribonucleolytic activity toward poly (U) (379.5 μ/mg), the second highest activity toward poly (C) (244.7 μ/mg), less activity toward poly (A) (167.4 μ/mg), and much weaker activity toward poly (G) (114.5 μ/mg). The RNase inhibited HIV-1 reverse transcriptase with an IC(50) of 65 μM. No effect on [(3)H-methyl]-thymidine uptake by lymphoma MBL2 cells and leukemia L1210 cells was observed at 100 μM concentration of the RNase. A comparison of RNases from S. commune and Volvariella volvacea revealed that they demonstrated some similarities in N-terminal amino acid sequence, optimum pH and polyhomoribonucleotide specificity. However, some differences in chromatographic behavior and molecular mass were observed.

OBJECTIVE

We evaluated genetic variants in 51 candidate genes encoding proteins that interact with HIV-1 during the virus life cycle for association with HIV-1 outcomes in an African cohort.

METHODS

Using a nested case-control study within a cohort of heterosexual HIV-1-serodiscordant couples, we genotyped 475 haplotype-tagging single-nucleotide polymorphisms (tagSNPs) and 18 SNPs previously associated with HIV-1 transmission and/or progression (candidate SNPs) in 51 host genes. We used logistic and Cox proportional hazard regression with adjustment for sex, age, and population stratification to detect SNP associations with HIV-1 acquisition, plasma HIV-1 set point, and a composite measure of HIV-1 disease progression. Significant thresholds for tagSNP, but not candidate SNP, associations were subjected to Bonferroni correction for multiple testing.

RESULTS

We evaluated 491 HIV-1-infected and 335 HIV-1-uninfected individuals for 493 SNPs, 459 of which passed quality control filters. Candidate SNP PPIA rs8177826 and tagSNP SMARCB1 rs6003904 were significantly associated with HIV-1 acquisition risk (odds ratio = 0.14, P = 0.03, and odds ratio = 2.11, Pcorr = 0.01, respectively). Furthermore, the TT genotype for CCR5 rs1799988 was associated with a mean 0.2 log10 copies per milliliter lower plasma HIV-1 RNA set point (P = 0.04). We also identified significant associations with HIV-1 disease progression for variants in FUT2 and MBL2.

CONCLUSIONS

Using a targeted gene approach, we identified variants in host genes whose protein products interact with HIV-1 during the virus replication cycle and were associated with HIV-1 outcomes in this African cohort.

Crohn' disease (CD) is a chronic idiopathic inflammatory bowel disease characterized by the interaction of both hereditary and environmental factors. Intestinal flora and pathogens such as bacteria, viruses and fungi, are thought to be the first step leading to an inflammatory status, which is subsequently amplified in genetically susceptible patients thus triggering the disease. Since the innate immune system is believed to be very important in regulating the flora of the gastrointestinal tract, we decided to study the influence of two important molecules of the innate immune system in CD. Frozen intestinal biopsies from 49 Crohn patients and 10 healthy individuals were collected at the gastroenterology unit of Children's Hospital Burlo Garofolo in Trieste and innate immunity gene expression was evaluated by using both in situ RT-PCR and quantitative PCR. We have analyzed the expression and localization of both MBL2 and DEFB1 genes in intestinal biopsies of Italian Crohn patients by in situ RT-PCR and quantitative PCR. DEFB1 is expressed equally in all subjects. Importantly, MBL2 transcripts were upregulated in CD patients compared to healthy controls. MBL2 expression in controls is normally extremely low, detectable only by quantitative PCR with a Taqman probe. We demonstrated the MBL2 and DEFB1 expression in intestinal biopsies of patients suffering from CD. Our results showed that the MBL2 gene is expressed by cells in the basal lamina, whilst DEFB1 is expressed by epithelial cells.

Background: Ergot alkaloids (E+) are mycotoxins produced by the endophytic fungus, Epichloë coenophiala, in tall fescue that are associated with ergotism in animals. Exposure to ergot alkaloids during gestation reduces fetal weight and placental mass in sheep. These reductions are related to vasoconstrictive effects of ergot alkaloids and potential alterations in nutrient transport to the fetus. Cotyledon samples were obtained from eight ewes that were fed E+ (n = 4; E+/E+) or E- (endophyte-free without ergot alkaloids; n = 4; E-/E-) seed during both mid (d 35 to 85) and late (d 85-133) gestation to assess differentially expressed genes associated with ergot alkaloid induced reductions in placental mass and fetal weight, and discover potential adaptive mechanisms to alter nutrient supply to fetus.

Results: Ewes fed E+/E+ fescue seed during both mid and late gestation had 20% reduction in fetal body weight and 33% reduction in cotyledon mass compared to controls (E-/E-). Over 13,000 genes were identified with 110 upregulated and 33 downregulated. Four genes had a |log2FC| > 5 for ewes consuming E+/E+ treatment compared to controls: LECT2, SLC22A9, APOC3, and MBL2. REViGO revealed clusters of upregulated genes associated glucose, carbohydrates, lipid, protein, macromolecular and cellular metabolism, regulation of wound healing and response to starvation. For downregulated genes, no clusters were present, but all enriched GO terms were associated with anion and monocarboxylic acid transport. The complement and coagulation cascade and the peroxisome proliferator-activated receptor signaling pathway were found to be enriched for ewes consuming E+/E+ treatment.

Conclusions: Consumption of ergot alkaloids during gestation altered the cotyledonary transcriptome specifically related to macronutrient metabolism, wound healing and starvation. These results show that ergot alkaloid exposure upregulates genes involved in nutrient metabolism to supply the fetus with additional substrates in attempts to rescue fetal growth.

Keywords: Cotyledon; Ergot alkaloid; Mycotoxin; Nutrient transport; Sheep; Vasoconstriction.