Influence of free and immobilized chitosan on a defined human gut microbial ecosystem

[EN] In this work, the influence of different forms of presentation of chitosan in the human gut microbiota with a defined bacterial community was evaluated. First, the susceptibility of individual gut bacterial isolates against chitosan was studied within a concentration range between 0.125 and 1 mg/mL. Then, the impact of chitosan (0.25 and 1 mg/mL) on a defined human gut microbial ecosystem was studied by metagenomic and metabonomic analyses. The results showed that chitosan in its free form had a high impact on individual isolates with a minimum inhibitory concentration below 1 mg/mL for most of the strains studied. In comparison, chitosan immobilized in the different carriers displayed a diverse effect on gut microbiota. The most susceptible strains were Agathobacter rectalis strain 16-6-I 1 FAA, Clostridium spiroforme strain 16-6-I 21 FAA and Mediterraneibacter faecis strain 16-6-I 30 FAA. The impact of the different modes of presentation of chitosan was strain-specific and species-specific when compared to results obtained from analysis of other strains within the genera Agathobacter, Clostridium and Mediterraneibacter, and therefore a study using a defined ecosystem was needed to extrapolate the results. Significant decreases in defined community richness and diversity and changes in metabolic profile were observed after exposure to free chitosan. Free chitosan produced significant reductions in the abundance of the genera Lachnoclostridium, Anaerotignum, Blautia, Enterococcus, Eubacterium and Ruthenibacterium together with a slight decrease of the production of SCFAs, among other fermentation by-products. The immobilized chitosan significantly alleviated the impact caused by the antimicrobial polymer and significantly increased the relative abundance of the Bacteroidetes phylum compared to free chitosan. These results suggest the significance of assessing the impact of new ingredients and materials included in food on the human gut microbiota with models that simulate the gastrointestinal environment, such as in vitro bioreactor systems.The authors gratefully acknowledge the financial support from the grant RTI2018-101599-B-C21 of the project "Retos Investigacion" funded by MCIN/AEI/10.13039/501100011033 and by "ERDF A way of making Europe". MRR acknowledges the Generalitat Valenciana for her postdoctoral fellowship (APOSTD/2019/118).Ruiz Rico, M.; Rendwick, S.; Vancuren, SJ.; Robinson, AV.; Gianetto-Hill, C.; Allen-Vercoe, E.; Barat Baviera, JM. (2022). Influence of free and immobilized chitosan on a defined human gut microbial ecosystem. Food Research International. 161:1-11. https://doi.org/10.1016/j.foodres.2022.11189011116

Ontology of core data mining entities

In this article, we present OntoDM-core, an ontology of core data mining entities. OntoDM-core defines themost essential datamining entities in a three-layered ontological structure comprising of a specification, an implementation and an application layer. It provides a representational framework for the description of mining structured data, and in addition provides taxonomies of datasets, data mining tasks, generalizations, data mining algorithms and constraints, based on the type of data. OntoDM-core is designed to support a wide range of applications/use cases, such as semantic annotation of data mining algorithms, datasets and results; annotation of QSAR studies in the context of drug discovery investigations; and disambiguation of terms in text mining. The ontology has been thoroughly assessed following the practices in ontology engineering, is fully interoperable with many domain resources and is easy to extend

The Nuts and Bolts of Einstein-Maxwell Solutions

We find new non-supersymmetric solutions of five-dimensional ungauged supergravity coupled to two vector multiplets. The solutions are regular, horizonless and have the same asymptotic charges as non-extremal charged black holes. An essential ingredient in our construction is a four-dimensional Euclidean base which is a solution to Einstein-Maxwell equations. We construct stationary solutions based on the Euclidean dyonic Reissner-Nordstrom black hole as well as a six-parameter family with a dyonic Kerr-Newman-NUT base. These solutions can be viewed as compactifications of eleven-dimensional supergravity on a six-torus and we discuss their brane interpretation.Comment: 29 pages, 3 figure

Comparative Developmental Expression Profiling of Two C. elegans Isolates

Gene expression is known to change during development and to vary among genetically diverse strains. Previous studies of temporal patterns of gene expression during C. elegans development were incomplete, and little is known about how these patterns change as a function of genetic background. We used microarrays that comprehensively cover known and predicted worm genes to compare the landscape of genetic variation over developmental time between two isolates of C. elegans. We show that most genes vary in expression during development from egg to young adult, many genes vary in expression between the two isolates, and a subset of these genes exhibit isolate-specific changes during some developmental stages. This subset is strongly enriched for genes with roles in innate immunity. We identify several novel motifs that appear to play a role in regulating gene expression during development, and we propose functional annotations for many previously unannotated genes. These results improve our understanding of gene expression and function during worm development and lay the foundation for linkage studies of the genetic basis of developmental variation in gene expression in this important model organism

Multiple Means to the Same End: The Genetic Basis of Acquired Stress Resistance in Yeast

In nature, stressful environments often occur in combination or close succession, and thus the ability to prepare for impending stress likely provides a significant fitness advantage. Organisms exposed to a mild dose of stress can become tolerant to what would otherwise be a lethal dose of subsequent stress; however, the mechanism of this acquired stress tolerance is poorly understood. To explore this, we exposed the yeast gene-deletion libraries, which interrogate all essential and non-essential genes, to successive stress treatments and identified genes necessary for acquiring subsequent stress resistance. Cells were exposed to one of three different mild stress pretreatments (salt, DTT, or heat shock) and then challenged with a severe dose of hydrogen peroxide (H2O2). Surprisingly, there was little overlap in the genes required for acquisition of H2O2 tolerance after different mild-stress pretreatments, revealing distinct mechanisms of surviving H2O2 in each case. Integrative network analysis of these results with respect to protein–protein interactions, synthetic–genetic interactions, and functional annotations identified many processes not previously linked to H2O2 tolerance. We tested and present several models that explain the lack of overlap in genes required for H2O2 tolerance after each of the three pretreatments. Together, this work shows that acquired tolerance to the same severe stress occurs by different mechanisms depending on prior cellular experiences, underscoring the context-dependent nature of stress tolerance

High-throughput profiling of caenorhabditis elegans starvation-responsive microRNAs

MicroRNAs (miRNAs) are non-coding RNAs of ~22 nucleotides in length that regulate gene expression by interfering with the stability and translation of mRNAs. Their expression is regulated during development, under a wide variety of stress conditions and in several pathological processes. In nature, animals often face feast or famine conditions. We observed that subjecting early L4 larvae from Caenorhabditis elegans to a 12-hr starvation period produced worms that are thinner and shorter than well-fed animals, with a decreased lipid accumulation, diminished progeny, reduced gonad size, and an increased lifespan. Our objective was to identify which of the 302 known miRNAs of C. elegans changed their expression under starvation conditions as compared to well-fed worms by means of deep sequencing in early L4 larvae. Our results indicate that 13 miRNAs (miR-34-3p, the family of miR-35-3p to miR-41-3p, miR-39-5p, miR-41-5p, miR-240-5p, miR-246-3p and miR-4813-5p) were upregulated, while 2 miRNAs (let-7-3p and miR-85-5p) were downregulated in 12-hr starved vs. well-fed early L4 larvae. Some of the predicted targets of the miRNAs that changed their expression in starvation conditions are involved in metabolic or developmental process. In particular, miRNAs of the miR-35 family were upregulated 6-20 fold upon starvation. Additionally, we showed that the expression of gld-1, important in oogenesis, a validated target of miR-35-3p, was downregulated when the expression of miR-35-3p was upregulated. The expression of another reported target, the cell cycle regulator lin-23, was unchanged during starvation. This study represents a starting point for a more comprehensive understanding of the role of miRNAs during starvation in C. elegans

Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. SIGNIFICANCE: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion-positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890