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- Fenton, Thomas M., et al.
(författare)
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Immune Profiling of Human Gut-Associated Lymphoid Tissue Identifies a Role for Isolated Lymphoid Follicles in Priming of Region-Specific Immunity
- 2020
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Ingår i: Immunity. - : Elsevier BV. - 1074-7613. ; 52:3, s. 557-570
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Tidskriftsartikel (refereegranskat)abstract
- The intestine contains some of the most diverse and complex immune compartments in the body. Here we describe a method for isolating human gut-associated lymphoid tissues (GALTs) that allows unprecedented profiling of the adaptive immune system in submucosal and mucosal isolated lymphoid follicles (SM-ILFs and M-ILFs, respectively) as well as in GALT-free intestinal lamina propria (LP). SM-ILF and M-ILF showed distinct patterns of distribution along the length of the intestine, were linked to the systemic circulation through MAdCAM-1+ high endothelial venules and efferent lymphatics, and had immune profiles consistent with immune-inductive sites. IgA sequencing analysis indicated that human ILFs are sites where intestinal adaptive immune responses are initiated in an anatomically restricted manner. Our findings position ILFs as key inductive hubs for regional immunity in the human intestine, and the methods presented will allow future assessment of these compartments in health and disease.
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| 2. |
- Niss, Kristoffer, et al.
(författare)
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Complete Topological Mapping of a Cellular Protein Interactome Reveals Bow-Tie Motifs as Ubiquitous Connectors of Protein Complexes
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 31:11
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Tidskriftsartikel (refereegranskat)abstract
- The network topology of a protein interactome is shaped by the function of each protein, making it a resource of functional knowledge in tissues and in single cells. Today, this resource is underused, as complete network topology characterization has proved difficult for large protein interactomes. We apply a matrix visualization and decoding approach to a physical protein interactome of a dendritic cell, thereby characterizing its topology with no prior assumptions of structure. We discover 294 proteins, each forming topological motifs called “bow-ties” that tie together the majority of observed protein complexes. The central proteins of these bow-ties have unique network properties, display multifunctional capabilities, are enriched for essential proteins, and are widely expressed in other cells and tissues. Collectively, the bow-tie motifs are a pervasive and previously unnoted topological trend in cellular interactomes. As such, these results provide fundamental knowledge on how intracellular protein connectivity is organized and operates. Niss et al. show that topological motifs called bow-ties create a scaffold within the cellular protein interactome that connects a majority of protein complexes. The central proteins of these motifs are found to be associated with multifunctionality and cellular essentiality, display unique network properties, and are expressed widely across cells and tissues.
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| 3. |
- Niss, Kristoffer, et al.
(författare)
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Effects of active farnesoid X receptor on GLUTag enteroendocrine L cells
- 2020
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 517
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Tidskriftsartikel (refereegranskat)abstract
- Activated transcription factor (TF) farnesoid X receptor (FXR) represses glucagon-like peptide-1 (GLP-1) secretion in enteroendocrine L cells. This, in turn, reduces insulin secretion, which is triggered when β cells bind GLP-1. Preventing FXR activation could boost GLP-1 production and insulin secretion. Yet, FXR's broader role in L cell biology still lacks understanding. Here, we show that FXR is a multifaceted TF in L cells using proteomics and gene expression data generated on GLUTag L cells. Most striking, 252 proteins regulated upon glucose stimulation have their abundances neutralized upon FXR activation. Mitochondrial repression or glucose import block are likely mechanisms of this. Further, FXR physically targets bile acid metabolism proteins, growth factors and other TFs, regulates ChREBP, while extensive text-mining found 30 FXR-regulated proteins to be well-known in L cell biology. Taken together, this outlines FXR as a powerful TF, where GLP-1 secretion block is just one of many downstream effects.
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| 4. |
- Varga, Tibor V., et al.
(författare)
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Association is not prediction : A landscape of confused reporting in diabetes – A systematic review
- 2020
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227. ; 170
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Appropriate analysis of big data is fundamental to precision medicine. While statistical analyses often uncover numerous associations, associations themselves do not convey predictive value. Confusion between association and prediction harms clinicians, scientists, and ultimately, the patients. We analyzed published papers in the field of diabetes that refer to “prediction” in their titles. We assessed whether these articles report metrics relevant to prediction. Methods: A systematic search was undertaken using NCBI PubMed. Articles with the terms “diabetes” and “prediction” were selected. All abstracts of original research articles, within the field of diabetes epidemiology, were searched for metrics pertaining to predictive statistics. Simulated data was generated to visually convey the differences between association and prediction. Results: The search-term yielded 2,182 results. After discarding non-relevant articles, 1,910 abstracts were evaluated. Of these, 39% (n = 745) reported metrics of predictive statistics, while 61% (n = 1,165) did not. The top reported metrics of prediction were ROC AUC, sensitivity and specificity. Using the simulated data, we demonstrated that biomarkers with large effect sizes and low P values can still offer poor discriminative utility. Conclusions: We demonstrate a landscape of confused reporting within the field of diabetes epidemiology where the term “prediction” is often incorrectly used to refer to association statistics. We propose guidelines for future reporting, and two major routes forward in terms of main analytic procedures and research goals: the explanatory route, which contributes to precision medicine, and the prediction route which contributes to personalized medicine.
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