| 1. |
- Jin, Chunsheng, et al.
(författare)
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Breast Milk Oligosaccharides Contain Immunomodulatory Glucuronic Acid and LacdiNAc
- 2023
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Ingår i: MOLECULAR & CELLULAR PROTEOMICS. - 1535-9484. ; 22:9
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Tidskriftsartikel (refereegranskat)abstract
- Breast milk is abundant with functionalized milk oligosaccharides (MOs) to nourish and protect the neonate. Yet we lack a comprehensive understanding of the repertoire and evolution of MOs across Mammalia. We report similar to 400 MO -species associations (>100 novel structures) from milk glycomics of nine mostly understudied species: alpaca, beluga whale, black rhinoceros, bottlenose dolphin, impala, L'Hoest's monkey, pygmy hippopotamus, domestic sheep, and striped dolphin. This revealed the hitherto unknown existence of the LacdiNAc motif (GalNAc beta 1-4GlcNAc) in MOs of all species except alpaca, sheep, and striped dolphin, indicating the widespread occurrence of this potentially antimicrobial motif in MOs. We also characterize glucuronic acid-containing MOs in the milk of impala, dolphins, sheep, and rhinoceros, previously only reported in cows. We demonstrate that these GlcA-MOs exhibit potent immunomodulatory effects. Our study extends the number of known MOs by >15%. Combined with >1900 curated MO -species associations, we characterize MO motif distributions, presenting an exhaustive overview of MO biodiversity.
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| 2. |
- Lundstrøm, Jon, et al.
(författare)
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LectinOracle: A Generalizable Deep Learning Model for Lectin-Glycan Binding Prediction
- 2022
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Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Ranging from bacterial cell adhesion over viral cell entry to human innate immunity, glycan-binding proteins or lectins are abound in nature. Widely used as staining and characterization reagents in cell biology and crucial for understanding the interactions in biological systems, lectins are a focal point of study in glycobiology. Yet the sheer breadth and depth of specificity for diverse oligosaccharide motifs has made studying lectins a largely piecemeal approach, with few options to generalize. Here, LectinOracle, a model combining transformer-based representations for proteins and graph convolutional neural networks for glycans to predict their interaction, is presented. Using a curated data set of 564,647 unique protein-glycan interactions, it is shown that LectinOracle predictions agree with literature-annotated specificities for a wide range of lectins. Using a range of specialized glycan arrays, it is shown that LectinOracle predictions generalize to new glycans and lectins, with qualitative and quantitative agreement with experimental data. It is further demonstrated that LectinOracle can be used to improve lectin classification, accelerate lectin directed evolution, predict epidemiological outcomes in the context of influenza virus, and analyze whole lectomes in host-microbe interactions. It is envisioned that the herein presented platform will advance both the study of lectins and their role in (glyco)biology.
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| 3. |
- Palm, Martin, et al.
(författare)
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The Effect of Heavy Metals on Conjugation Efficiency of an F-Plasmid in Escherichia coli.
- 2022
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Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Conjugation, the process by which conjugative plasmids are transferred between bacteria, is regarded as a major contributor to the spread of antibiotic resistance, in both environmental and clinical settings. Heavy metals are known to co-select for antibiotic resistance, but the impact of the presence of these metals on conjugation itself is not clear. Here, we systematically investigate the impact that five heavy metals (arsenic, cadmium, copper, manganese, and zinc) have on the transfer of an IncF conjugative plasmid in Escherichia coli. Our results show that two of the metals, cadmium and manganese, have no significant impact, while arsenic and zinc both reduce conjugation efficiency by approximately 2-fold. Copper showed the largest impact, with an almost 100-fold decrease in conjugation efficiency. This was not mediated by any change in transcription from the major Py promoter responsible for transcription of the conjugation machinery genes. Further, we show that in order to have this severe impact on the transfer of the plasmid, copper sulfate needs to be present during the mating process, and we suggest explanations for this.
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