| 1. |
- Crucianelli, Laura, et al.
(författare)
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Visuo-thermal congruency modulates the sense of body ownership
- 2022
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Ingår i: Communications Biology. - Stockholm : Karolinska Institutet, Dept of Neuroscience. - 2399-3642.
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Tidskriftsartikel (refereegranskat)abstract
- Thermosensation has been redefined as an interoceptive modality that provides information about the homeostatic state of the body. However, the contribution of thermosensory signals to the sense of body ownership remains unclear. Across two rubber hand illusion (RHI) experiments (N = 73), we manipulated the visuo-thermal congruency between the felt and seen temperature, on the real and rubber hand respectively. We measured the subjectively experienced RHI, the perceived hand location and temperature of touch, and monitored skin temperature. We found that visuo-thermal incongruencies between the seen and felt touch reduced the subjective and behavioural RHI experience (Experiment 1). Visuo-thermal incongruencies also gave rise to a visuo-thermal illusion effect, but only when the rubber hand was placed in a plausible position (Experiment 2) and when considering individual differences in interoceptive sensibility. Thus, thermosensation contributes to the sense of body ownership by a mechanism of dynamic integration of visual and thermosensory signals.
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| 2. |
- Adler, Jeremy, et al.
(författare)
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Conventional analysis of movement on non-flat surfaces like the plasma membrane makes Brownian motion appear anomalous.
- 2019
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Cells are neither flat nor smooth, which has serious implications for prevailing plasma membrane models and cellular processes like cell signalling, adhesion and molecular clustering. Using probability distributions from diffusion simulations, we demonstrate that 2D and 3D Euclidean distance measurements substantially underestimate diffusion on non-flat surfaces. Intuitively, the shortest within surface distance (SWSD), the geodesic distance, should reduce this problem. The SWSD is accurate for foldable surfaces but, although it outperforms 2D and 3D Euclidean measurements, it still underestimates movement on deformed surfaces. We demonstrate that the reason behind the underestimation is that topographical features themselves can produce both super- and subdiffusion, i.e. the appearance of anomalous diffusion. Differentiating between topography-induced and genuine anomalous diffusion requires characterising the surface by simulating Brownian motion on high-resolution cell surface images and a comparison with the experimental data.
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| 3. |
- Agback, Tatiana, et al.
(författare)
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Combined NMR and molecular dynamics conformational filter identifies unambiguously dynamic ensembles of Dengue protease NS2B/NS3pro
- 2023
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Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- The dengue protease NS2B/NS3pro has been reported to adopt either an 'open' or a 'closed' conformation. We have developed a conformational filter that combines NMR with MD simulations to identify conformational ensembles that dominate in solution. Experimental values derived from relaxation parameters for the backbone and methyl side chains were compared with the corresponding back-calculated relaxation parameters of different conformational ensembles obtained from free MD simulations. Our results demonstrate a high prevalence for the 'closed' conformational ensemble while the 'open' conformation is absent, indicating that the latter conformation is most probably due to crystal contacts. Conversely, conformational ensembles in which the positioning of the co-factor NS2B results in a 'partially' open conformation, previously described in both MD simulations and X-ray studies, were identified by our conformational filter. Altogether, we believe that our approach allows for unambiguous identification of true conformational ensembles, an essential step for reliable drug discovery. A conformational filter that combines NMR with MD simulations to identify conformational ensembles that dominate in solution suggests dengue protease NS2B/NS3pro predominantly exists in a "closed" conformation.
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| 4. |
- Akusjarvi, SS, et al.
(författare)
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Peripheral blood CD4+CCR6+ compartment differentiates HIV-1 infected or seropositive elite controllers from long-term successfully treated individuals
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 357-
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 infection induces a chronic inflammatory environment not restored by suppressive antiretroviral therapy (ART). As of today, the effect of viral suppression and immune reconstitution in people living with HIV-1 (PLWH) has been well described but not completely understood. Herein, we show how PLWH who naturally control the virus (PLWHEC) have a reduced proportion of CD4+CCR6+and CD8+CCR6+cells compared to PLWH on suppressive ART (PLWHART) and HIV-1 negative controls (HC). Expression of CCR2 was reduced on both CD4+, CD8+and classical monocytes in PLWHECcompared to PLWHARTand HC. Longer suppressive therapy, measured in the same patients, decreased number of cells expressing CCR2 on all monocytic cell populations while expression on CD8+T cells increased. Furthermore, the CD4+CCR6+/CCR6−cells exhibited a unique proteomic profile with a modulated energy metabolism in PLWHECcompared to PLWHARTindependent of CCR6 status. The CD4+CCR6+cells also showed an enrichment in proteins involved in apoptosis and p53 signalling in PLWHECcompared to PLWHART, indicative of increased sensitivity towards cell death mechanisms. Collectively, this data shows how PLWHEChave a unique chemokine receptor profile that may aid in facilitating natural control of HIV-1 infection.
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| 5. |
- Allen, MD, et al.
(författare)
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SWI/SNF subunit BAF155 N-terminus structure informs the impact of cancer-associated mutations and reveals a potential drug binding site
- 2021
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 528-
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Tidskriftsartikel (refereegranskat)abstract
- SWI/SNF (BAF) chromatin remodelling complexes are key regulators of gene expression programs, and attractive drug targets for cancer therapies. Here we show that the N-terminus of the BAF155/SMARCC1 subunit contains a putative DNA-binding MarR-like domain, a chromodomain and a BRCT domain that are interconnected to each other to form a distinct module. In this structure the chromodomain makes interdomain interactions and has lost its canonical function to bind to methylated lysines. The structure provides new insights into the missense mutations that target this module in cancer. This study also reveals two adjacent, highly-conserved pockets in a cleft between the domains that form a potential binding site, which can be targeted with small molecules, offering a new strategy to target SWI/SNF complexes.
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| 6. |
- Almeida, Jorge, et al.
(författare)
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Neural and behavioral signatures of the multidimensionality of manipulable object processing
- 2023
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Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding how we recognize objects requires unravelling the variables that govern the way we think about objects and the neural organization of object representations. A tenable hypothesis is that the organization of object knowledge follows key object-related dimensions. Here, we explored, behaviorally and neurally, the multidimensionality of object processing. We focused on within-domain object information as a proxy for the decisions we typically engage in our daily lives - e.g., identifying a hammer in the context of other tools. We extracted object-related dimensions from subjective human judgments on a set of manipulable objects. We show that the extracted dimensions are cognitively interpretable and relevant - i.e., participants are able to consistently label them, and these dimensions can guide object categorization; and are important for the neural organization of knowledge - i.e., they predict neural signals elicited by manipulable objects. This shows that multidimensionality is a hallmark of the organization of manipulable object knowledge. By obtaining human subjective judgments on a large set of manipulable objects this study provides a set of object-related dimensions and demonstrates that these dimensions are important for the neural and mental representations we hold about objects.
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| 7. |
- Alneberg, Johannes, et al.
(författare)
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Ecosystem-wide metagenomic binning enables prediction of ecological niches from genomes
- 2020
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Ingår i: Communications Biology. - : Nature Publishing Group. - 2399-3642. ; 3:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Alneberg et al. conduct metagenomics binning of water samples collected over major environmental gradients in the Baltic Sea. They use machine-learning to predict the placement of genome clusters along niche gradients based on the content of functional genes. The genome encodes the metabolic and functional capabilities of an organism and should be a major determinant of its ecological niche. Yet, it is unknown if the niche can be predicted directly from the genome. Here, we conduct metagenomic binning on 123 water samples spanning major environmental gradients of the Baltic Sea. The resulting 1961 metagenome-assembled genomes represent 352 species-level clusters that correspond to 1/3 of the metagenome sequences of the prokaryotic size-fraction. By using machine-learning, the placement of a genome cluster along various niche gradients (salinity level, depth, size-fraction) could be predicted based solely on its functional genes. The same approach predicted the genomes' placement in a virtual niche-space that captures the highest variation in distribution patterns. The predictions generally outperformed those inferred from phylogenetic information. Our study demonstrates a strong link between genome and ecological niche and provides a conceptual framework for predictive ecology based on genomic data.
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| 8. |
- Andersson, Alma, et al.
(författare)
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Single-cell and spatial transcriptomics enables probabilistic inference of cell type topography
- 2020
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Ingår i: Communications Biology. - : Nature Research. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The field of spatial transcriptomics is rapidly expanding, and with it the repertoire of available technologies. However, several of the transcriptome-wide spatial assays do not operate on a single cell level, but rather produce data comprised of contributions from a – potentially heterogeneous – mixture of cells. Still, these techniques are attractive to use when examining complex tissue specimens with diverse cell populations, where complete expression profiles are required to properly capture their richness. Motivated by an interest to put gene expression into context and delineate the spatial arrangement of cell types within a tissue, we here present a model-based probabilistic method that uses single cell data to deconvolve the cell mixtures in spatial data. To illustrate the capacity of our method, we use data from different experimental platforms and spatially map cell types from the mouse brain and developmental heart, which arrange as expected.
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| 9. |
- Andersson, Natalie, et al.
(författare)
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DEVOLUTION—A method for phylogenetic reconstruction of aneuploid cancers based on multiregional genotyping data
- 2021
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Phylogenetic reconstruction of cancer cell populations remains challenging. There is a particular lack of tools that deconvolve clones based on copy number aberration analyses of multiple tumor biopsies separated in time and space from the same patient. This has hampered investigations of tumors rich in aneuploidy but few point mutations, as in many childhood cancers and high-risk adult cancer. Here, we present DEVOLUTION, an algorithm for subclonal deconvolution followed by phylogenetic reconstruction from bulk genotyping data. It integrates copy number and sequencing information across multiple tumor regions throughout the inference process, provided that the mutated clone fraction for each mutation is known. We validate DEVOLUTION on data from 56 pediatric tumors comprising 253 tumor biopsies and show a robust performance on simulations of bulk genotyping data. We also benchmark DEVOLUTION to similar bioinformatic tools using an external dataset. DEVOLUTION holds the potential to facilitate insights into the development, progression, and response to treatment, particularly in tumors with high burden of chromosomal copy number alterations.
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| 10. |
- Arellano-Caicedo, Carlos, et al.
(författare)
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Habitat geometry in artificial microstructure affects bacterial and fungal growth, interactions, and substrate degradation
- 2021
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Microhabitat conditions determine the magnitude and speed of microbial processes but have been challenging to investigate. In this study we used microfluidic devices to determine the effect of the spatial distortion of a pore space on fungal and bacterial growth, interactions, and substrate degradation. The devices contained channels differing in bending angles and order. Sharper angles reduced fungal and bacterial biomass, especially when angles were repeated in the same direction. Substrate degradation was only decreased by sharper angles when fungi and bacteria were grown together. Investigation at the cellular scale suggests that this was caused by fungal habitat modification, since hyphae branched in sharp and repeated turns, blocking the dispersal of bacteria and the substrate. Our results demonstrate how the geometry of microstructures can influence microbial activity. This can be transferable to soil pore spaces, where spatial occlusion and microbial feedback on microstructures is thought to explain organic matter stabilization.
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