Biology subjects

Contreras, M.

Publications and source records attributed to Contreras, M..

24 records · Page 2Linked to original sources

bioRxiv2021

Landscapes and bacterial signatures of mucosa-associated intestinal microbiota in Chilean and Spanish patients with inflammatory bowel disease

Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohns disease (CD), cause chronic inflammation of the gut, affecting millions of people worldwide. IBD have been frequently associated with an alteration of the gut microbiota, termed dysbiosis, which is generally characterized by an increase in abundance of Proteobacteria such as Escherichia coli, and a decrease in abundance of Firmicutes such as Faecalibacterium prausnitzii (an indicator of a healthy colonic microbiota). The mechanisms behind the development of the IBD and the dysbiosis are incompletely understood. Using samples from colonic biopsies, we studied the mucosa-associated intestinal microbiota in Chilean and Spanish patients with IBD. In agreement with previous studies, microbiome comparison between IBD patients and non-IBD controls indicated that dysbiosis in these patients is characterized by an increase of pro-inflammatory bacteria (mostly Proteobacteria) and a decrease of commensal beneficial bacteria (mostly Firmicutes). Notably, bacteria typically residing on the mucosa of healthy individuals were mostly obligate anaerobes, whereas in the inflamed mucosa an increase of facultative anaerobe and aerobic bacteria was observed. We also identify potential co-occurring and mutually exclusive interactions between bacteria associated with the healthy and inflamed mucosa, which appear to be determined by the oxygen availability and the type of respiration. Finally, we identify a panel of bacterial biomarkers that allow the discrimination between eubiosis from dysbiosis with a high diagnostic performance (96% accurately), which could be used for the development of non-invasive diagnostic methods. Thus, this study is a step forward toward understanding the landscapes and alterations of mucosa-associated intestinal microbiota in patients with IBD.

microbiology↗

bioRxiv2020

The antibody response to the glycan α-Gal correlates with COVID-19 disease symptoms

The coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. The characterization of the immunological mechanisms involved in disease symptomatology and protective response is important to advance in disease control and prevention. Humans evolved by losing the capacity to synthesize the glycan Gal1-3Gal{beta}1-(3)4GlcNAc-R (-Gal), which resulted in the development of a protective response against pathogenic viruses and other microorganisms containing this modification on membrane proteins mediated by anti--Gal IgM/IgG antibodies produced in response to bacterial microbiota. In addition to anti--Gal antibody-mediated pathogen opsonization, this glycan induces various immune mechanisms that have shown protection in animal models against infectious diseases without inflammatory responses. In this study, we hypothesized that the immune response to -Gal may contribute to the control of COVID-19. To address this hypothesis, we characterized the antibody response to -Gal in patients at different stages of COVID-19 and in comparison with healthy control individuals. The results showed that while the inflammatory response and the anti-SARS-CoV-2 (Spike) IgG antibody titers increased, reduction in anti--Gal IgE, IgM and IgG antibody titers and alteration of anti--Gal antibody isotype composition correlated with COVID-19 severity. The results suggested that the inhibition of the -Gal-induced immune response may translate into more aggressive viremia and severe disease inflammatory symptoms. These results support the proposal of developing interventions such as probiotics based on commensal bacteria with -Gal epitopes to modify the microbiota and increase the -Gal-induced protective immune response and reduce the severity of COVID-19.

immunology↗

bioRxiv2020

Pairwise and Higher-Order Epistatic Interactions Have a Significant Impact on Bronchodilator Drug Response in African American Youth with Asthma

BackgroundAsthma is one of the leading chronic illnesses among children in the United States. Asthma prevalence is higher among African Americans (11.2%) compared to European Americans (7.7%). Bronchodilator medications are part of the first-line therapy, and the rescue medication, for acute asthma symptoms. Bronchodilator drug response (BDR) varies substantially among different racial/ethnic groups. Asthma prevalence in African Americans is only 3.5% higher than that of European Americans, however, asthma mortality among African Americans is four times that of European Americans; variation in BDR may play an important role in explaining this health disparity. To improve our understanding of disparate health outcomes in complex phenotypes such as BDR, it is important to consider interactions between environmental and biological variables. ResultsWe evaluated the impact of pairwise and three-variable interactions between environmental, social, and biological variables on BDR in 617 African American youth with asthma using Visualization of Statistical Epistasis Networks (ViSEN). ViSEN is a non-parametric entropy-based approach able to identify interaction effects. We performed analyses in the full dataset and in sex-stratified subsets. Analysis in the full dataset identified six significant interactions associated with BDR, the strongest of which was an interaction between prenatal smoke exposure, age, and global African ancestry (IG: 1.09%, p=0.005). Sex-stratified analyses yielded additional significant, but divergent, results for females and males, indicating the presence of sex-specific effects. ConclusionsOur study identified novel interaction effects significantly influencing BDR in African American children with asthma. Notably, we found that the impact of higher-order interactions was greater than that of pairwise or main effects on BDR highlighting the complexity of the network of genetic and environmental factors impacting this phenotype. Several associations uncovered by ViSEN would not have been detected using regression-based methods emphasizing the importance of employing statistical methods optimized to detect both linear and non-linear interaction effects when studying complex phenotypes such as BDR. The information gained in this study increases our understanding and appreciation of the complex nature of the interactions between environmental and health-related factors that influence BDR and will be invaluable to biomedical researchers designing future studies.

bioinformatics↗

bioRxiv2019

Analysis of co-regulated abundance of genes associated with arsenic and phosphate metabolism in Andean Microbial Ecosystems

Phosphate and arsenate are very similar compounds, and there is great interest in studying their relationship and their interaction with biological systems. Despite having no apparent biological function, specific genes regulate arsenic interaction with cells and can be located in regions of the genome called arsenic islands, where phosphate metabolism genes are also present. Although they are neighboring genes, the nature of their relationship and how they have been selected is still unknown. In this work, we analyzed the metagenomes of the four microbial ecosystems inhabiting hypersaline lakes of the Argentine Puna and the Atacama salt flat in Chile and have evaluated the presence and abundance of both arsenic and phosphate metabolism genes. The samples analyzed included microbialites, biofilms and microbial mats; all of them established under high arsenic concentrations, high UV radiation and high temperature fluctuation, among others. The results show great differences in the dispersion and abundance of genes related to both phosphate and arsenic metabolism in the analyzed samples. The main difference is given in the Diamante Lake, located in the crater of the Galan volcano characterized by being one of the lakes with the highest arsenic concentration (2.34 mM). Correlating genes abundance with the physicochemical parameters of the lakes studied, our results suggest that arsenic and phosphate metabolism are intricately co-regulated in environmental conditions.

genomics↗

bioRxiv2019

An N-terminal motif in NLR immune receptors is functionally conserved across distantly related plant species

The molecular codes underpinning the functions of plant NLR immune receptors are poorly understood. We used in vitro Mu transposition to generate a random truncation library and identify the minimal functional region of NLRs. We applied this method to NRC4--a helper NLR that functions with multiple sensor NLRs within a Solanaceae receptor network. This revealed that the NRC4 N-terminal 29 amino acids are sufficient to induce hypersensitive cell death. This region is defined by the consensus MADAxVSFxVxKLxxLLxxEx (MADA motif) that is conserved at the N-termini of NRC family proteins and ~20% of coiled-coil (CC)-type plant NLRs. The MADA motif matches the N-terminal 1 helix of Arabidopsis NLR protein ZAR1, which undergoes a conformational switch during resistosome activation. Immunoassays revealed that the MADA motif is functionally conserved across NLRs from distantly related plant species. NRC-dependent sensor NLRs lack MADA sequences indicating that this motif has degenerated in sensor NLRs over evolutionary time.

plant biology↗

bioRxiv2019

Assessing the multiple dimensions of poverty. Data mining approaches to the 2004-14 Health and Demographic Surveillance System in Cuatro Santos, Nicaragua

We aimed to describe multiple dimensions of poverty according to the capability approach theory by applying data mining approaches to the Cuatro Santos Health and Demographic Surveillance databases, Nicaragua. Four municipalities in northern Nicaragua constitute the Cuatro Santos area, with 25,893 inhabitants in 5,966 households (2014). A local process analyzing poverty-related problems and prioritizing suggested actions, was initiated 1997 based on a community action plan 2002-2015. Priority interventions were school breakfasts, environmental protection, water and sanitation, preventive healthcare, home gardening, micro credits, technical training, stipends for university education, and the use of Internet. In 2004, a survey of basic health and demographic information was performed in the whole population followed by surveillance updates in 2007, 2009, and 2014 linking households and individuals by unique identifiers. Information included the house (floor, walls) and services (water, sanitation, electricity) as well as demographic data (birth, deaths, migration). Data on participation in interventions, on food security, household assets, and womens self-rated health were collected in 2014. A K-means algorithm were used to cluster the household data (54 variables). The poverty ranking of household clusters using the unsatisfied basic needs index (UBN) variables changed when including variables describing basic capabilities. The households in the fairly rich cluster, having assets as motorbikes and computers were described as modern. Those in the fairly poor cluster, having different degrees of food insecurity were labeled vulnerable. Poor and poorest clusters of households were traditional e.g. in using horses for transport. Results displayed a society transforming from traditional to a modern, where the forerunners were not the richest but educated, had more working members of household, fewer children and were food secure. Those lagging were the poor, traditional and food insecure. The approach and results may be useful for an improved understanding of poverty and to direct local interventions.

epidemiology↗