RESUMO
For decades, parasitic worms such as Trichuris muris have been maintained in laboratory animals, providing insights into host-parasite interactions and host immune responses. The most used T. muris isolate is the E isolate, established in the laboratory in 1954. However, one concern with these model systems is the potential for laboratory-induced selection and therefore changes in host-parasite interactions. To address these concerns, we compare the E isolate with a recently isolated T. muris isolate (M isolate), established from wild house mice (Mus musculus domesticus, Isle of May, UK), in their capacity to infect laboratory mice. High dose infection of C57BL/6 mice revealed that significantly more parasites of the M isolate survived to the adult stage compared to the E isolate. Worm persistence was associated with heightened TNF-α and IL-10 secretion upon parasite-specific re-stimulation, and higher serum IgG1 and IgG2c levels, concomitant with an increase in T-bet+ and ICOS+ CD4+ T effector-memory cells. Differences in host response to the isolates were not as pronounced during low dose infection. Our study highlights the need for regular evaluation of lab-maintained parasite isolates against freshly isolated parasites to understand whether the established lab strains remain relevant model systems for our understanding of parasitic infections.
Assuntos
Interações Hospedeiro-Parasita , Camundongos Endogâmicos C57BL , Tricuríase , Trichuris , Animais , Trichuris/isolamento & purificação , Trichuris/imunologia , Tricuríase/parasitologia , Tricuríase/imunologia , Camundongos , Interações Hospedeiro-Parasita/imunologia , Imunoglobulina G/sangue , Feminino , Anticorpos Anti-Helmínticos/sangue , Linfócitos T CD4-Positivos/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-10/sangueRESUMO
For most eukaryotes, sexual reproduction is a fundamental process that requires meiosis. In turn, meiosis typically depends on a reciprocal exchange of DNA between each pair of homologous chromosomes, known as a crossover (CO), to ensure proper chromosome segregation. The frequency and distribution of COs are regulated by intrinsic and extrinsic environmental factors, but much more is known about the molecular mechanisms governing the former compared to the latter. Here we show that elevated temperature induces meiotic hyper-recombination in Arabidopsis thaliana and we use genetic analysis with mutants in different recombination pathways to demonstrate that the extra COs are derived from the major Type I interference sensitive pathway. We also show that heat-induced COs are not the result of an increase in DNA double-strand breaks and that the hyper-recombinant phenotype is likely specific to thermal stress rather than a more generalized stress response. Taken together, these findings provide initial mechanistic insight into how environmental cues modulate plant meiotic recombination and may also offer practical applications.
Assuntos
Arabidopsis/genética , Troca Genética , Meiose/genética , Temperatura , Segregação de Cromossomos/genética , Cromossomos de Plantas/genética , Regulação da Expressão Gênica de Plantas , Recombinação Homóloga , Mutação , FenótipoRESUMO
Motivation: Structural analysis of glycans poses significant challenges in glycobiology due to their complex sequences. Research questions such as analyzing the sequence content of the α1-6 branch in N-glycans, are biologically meaningful yet can be hard to automate. Results: Here, we introduce a regular expression system, designed for glycans, feature-complete, and closely aligned with regular expression formatting. We use this to annotate glycan motifs of arbitrary complexity, perform differential expression analysis on designated sequence stretches, or elucidate branch-specific binding specificities of lectins in an automated manner. We are confident that glycan regular expressions will empower computational analyses of these sequences. Availability and implementation: Our regular expression framework for glycans is implemented in Python and is incorporated into the open-source glycowork package (version 1.1+). Code and documentation are available at https://github.com/BojarLab/glycowork/blob/master/glycowork/motif/regex.py.
RESUMO
Mucin protein glycosylation is important in determining biological properties of mucus gels, which form protective barriers at mucosal surfaces of the body such as the intestine. Ecological factors including: age, sex, and diet can change mucus barrier properties by modulating mucin glycosylation. However, as our understanding stems from controlled laboratory studies in house mice, the combined influence of ecological factors on mucin glycosylation in real-world contexts remains limited. In this study, we used histological staining with 'Alcian Blue, Periodic Acid, Schiff's' and 'High-Iron diamine' to assess the acidic nature of mucins stored within goblet cells of the intestine, in a wild mouse population (Mus musculus). Using statistical models, we identified sex as among the most influential ecological factors determining the acidity of intestinal mucin glycans in wild mice. Our data from wild mice and experiments using laboratory mice suggest estrogen signalling associates with an increase in the relative abundance of sialylated mucins. Thus, estrogen signalling may underpin sex differences observed in the colonic mucus of wild and laboratory mice. These findings highlight the significant influence of ecological parameters on mucosal barrier sites and the complementary role of wild populations in augmenting standard laboratory studies in the advancement of mucus biology.