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| 5. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 7. |
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| 8. |
- Zaborowski, AM, et al.
(författare)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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| 9. |
- Brachi, B., et al.
(författare)
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Plant genetic effects on microbial hubs impact host fitness in repeated field trials
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
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Tidskriftsartikel (refereegranskat)abstract
- Although complex interactions between hosts and microbial associates are increasingly well documented, we still know little about how and why hosts shape microbial communities in nature. In addition, host genetic effects on microbial communities vary widely depending on the environment, obscuring conclusions about which microbes are impacted and which plant functions are important. We characterized the leaf microbiota of 200 Arabidopsis thaliana genotypes in eight field experiments and detected consistent host effects on specific, broadly distributed microbial species (operational taxonomic unit [OTUs]). Host genetic effects disproportionately influenced central ecological hubs, with heritability of particular OTUs declining with their distance from the nearest hub within the microbial network. These host effects could reflect either OTUs preferentially associating with specific genotypes or differential microbial success within them. Host genetics associated with microbial hubs explained over 10% of the variation in lifetime seed production among host genotypes across sites and years. We successfully cultured one of these microbial hubs and demonstrated its growth-promoting effects on plants in sterile conditions. Finally, genome-wide association mapping identified many putatively causal genes with small effects on the relative abundance of microbial hubs across sites and years, and these genes were enriched for those involved in the synthesis of specialized metabolites, auxins, and the immune system. Using untargeted metabolomics, we corroborate the consistent association between variation in specialized metabolites and microbial hubs across field sites. Together, our results reveal that host genetic variation impacts the microbial communities in consistent ways across environments and that these effects contribute to fitness variation among host genotypes.
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| 10. |
- Bissinger, Rosi, et al.
(författare)
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Thrombospondin-1/CD47 signaling modulates transmembrane cation conductance, survival, and deformability of human red blood cells
- 2020
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Ingår i: Cell Communication and Signaling. - : Springer Nature. - 1478-811X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Thrombospondin-1 (TSP-1), a Ca2+-binding trimeric glycoprotein secreted by multiple cell types, has been implicated in the pathophysiology of several clinical conditions. Signaling involving TSP-1, through its cognate receptor CD47, orchestrates a wide array of cellular functions including cytoskeletal organization, migration, cell-cell interaction, cell proliferation, autophagy, and apoptosis. In the present study, we investigated the impact of TSP-1/CD47 signaling on Ca2+ dynamics, survival, and deformability of human red blood cells (RBCs).Methods: Whole-cell patch-clamp was employed to examine transmembrane cation conductance. RBC intracellular Ca2+ levels and multiple indices of RBC cell death were determined using cytofluorometry analysis. RBC morphology and microvesiculation were examined using imaging flow cytometry. RBC deformability was measured using laser-assisted optical rotational cell analyzer.Results: Exposure of RBCs to recombinant human TSP-1 significantly increased RBC intracellular Ca2+ levels. As judged by electrophysiology experiments, TSP-1 treatment elicited an amiloride-sensitive inward current alluding to a possible Ca2+ influx via non-selective cation channels. Exogenous TSP-1 promoted microparticle shedding as well as enhancing Ca2+- and nitric oxide-mediated RBC cell death. Monoclonal (mouse IgG1) antibody-mediated CD47 ligation using 1F7 recapitulated the cell death-inducing effects of TSP-1. Furthermore, TSP-1 treatment altered RBC cell shape and stiffness (maximum elongation index).Conclusions: Taken together, our data unravel a new role for TSP-1/CD47 signaling in mediating Ca2+ influx into RBCs, a mechanism potentially contributing to their dysfunction in a variety of systemic diseases.
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| 11. |
- Alonso-Blanco, Carlos, et al.
(författare)
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1,135 Genomes Reveal the Global Pattern of Polymorphism in Arabidopsis thaliana
- 2016
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 481-491
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Tidskriftsartikel (refereegranskat)abstract
- Arabidopsis thaliana serves as a model organism for the study of fundamental physiological, cellular, and molecular processes. It has also greatly advanced our understanding of intraspecific genome variation. We present a detailed map of variation in 1,135 high-quality re-sequenced natural inbred lines representing the native Eurasian and North African range and recently colonized North America. We identify relict populations that continue to inhabit ancestral habitats, primarily in the Iberian Peninsula. They have mixed with a lineage that has spread to northern latitudes from an unknown glacial refugium and is now found in a much broader spectrum of habitats. Insights into the history of the species and the fine-scale distribution of genetic diversity provide the basis for full exploitation of A. thaliana natural variation through integration of genomes and epigenomes with molecular and non-molecular phenotypes.
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| 12. |
- Banas, Indra, et al.
(författare)
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Spatio-functional organization in virocells of small uncultivated archaea from the deep biosphere
- 2023
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Ingår i: The ISME Journal. - : Springer Nature. - 1751-7362 .- 1751-7370. ; 17, s. 1789-1792
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Tidskriftsartikel (refereegranskat)abstract
- Despite important ecological roles posited for virocells (i.e., cells infected with viruses), studying individual cells in situ is technically challenging. We introduce here a novel correlative microscopic approach to study the ecophysiology of virocells. By conducting concerted virusFISH, 16S rRNA FISH, and scanning electron microscopy interrogations of uncultivated archaea, we linked morphologies of various altiarchaeal cells to corresponding phylogenetic signals and indigenous virus infections. While uninfected cells exhibited moderate separation between fluorescence signals of ribosomes and DNA, virocells displayed complete cellular segregation of chromosomal DNA from viral DNA, the latter co-localizing with host ribosome signals. A similar spatial separation was observed in dividing cells, with viral signals congregating near ribosomes at the septum. These observations suggest that replication of these uncultivated viruses occurs alongside host ribosomes, which are used to generate the required proteins for virion assembly. Heavily infected cells sometimes displayed virus-like particles attached to their surface, which agree with virus structures in cells observed via transmission electron microscopy. Consequently, this approach is the first to link genomes of uncultivated viruses to their respective structures and host cells. Our findings shed new light on the complex ecophysiology of archaeal virocells in deep subsurface biofilms and provide a solid framework for future in situ studies of virocells.
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| 13. |
- Kawakatsu, Taiji, et al.
(författare)
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Epigenomic Diversity in a Global Collection of Arabidopsis thaliana Accessions
- 2016
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 492-505
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Tidskriftsartikel (refereegranskat)abstract
- The epigenome orchestrates genome accessibility, functionality, and three-dimensional structure. Because epigenetic variation can impact transcription and thus phenotypes, it may contribute to adaptation. Here, we report 1,107 high-quality single-base resolution methylomes and 1,203 transcriptomes from the 1001 Genomes collection of Arabidopsis thaliana. Although the genetic basis of methylation variation is highly complex, geographic origin is a major predictor of genome-wide DNA methylation levels and of altered gene expression caused by epialleles. Comparison to cistrome and epicistrome datasets identifies associations between transcription factor binding sites, methylation, nucleotide variation, and co-expression modules. Physical maps for nine of the most diverse genomes reveal how transposons and other structural variants shape the epigenome, with dramatic effects on immunity genes. The 1001 Epigenomes Project provides a comprehensive resource for understanding how variation in DNA methylation contributes to molecular and non-molecular phenotypes in natural populations of the most studied model plant.
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| 14. |
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| 15. |
- Mata, Erika, et al.
(författare)
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Climate Mitigation from Circular and Sharing Economy in the Buildings Sector
- 2020
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Ingår i: Resources, Conservation and Recycling. - : Elsevier BV. - 0921-3449 .- 1879-0658. ; 158
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Tidskriftsartikel (refereegranskat)abstract
- The buildings sector is a major consumer of energy and resources throughout the entire life cycle of the buildings (materials sourcing, design, manufacturing, distribution, consumption, disposal) with corresponding greenhouse gas (GHG) emissions. The contribution of the sector is therefore key to achieving ambitious climate targets. In particular, to maintain global warming below target of 1.5 °C, a carbon dioxide emissions reduction of 9 Gt is required just from the global building sector (Wang et al, 2018). This will need to be achieved by a reduction in energy consumption and decarbonization of electricity production. Equally substantial reductions are required from the other life cycle phases: materials production, construction and demolition phases, which are typically accounted as changes in the industrial sector. The improvement of resource flows through a Circular Economy (CE) approach that includes reducing, reusing, recycling and recovering materials and products, facilitates a decoupling of growth from resource consumption (Kalmykova et al, 2018). This can provide clear advantages from an environmental perspective, contributing to Sustainable Development Goals and to climate change mitigation. However, the literature has identified that despite a global trend of improved operational performance, there are rising “embodied” emissions from processing and manufacturing of building materials. Industrial recycling and energy recovery are the most common practices, even when reuse is believed to have higher economic and environmental value (Eberhardt et al, 2019). The Sharing Economy (SE), offers several opportunities for the building sector by promoting reuse, enabling shared ownership, access or use to increase the utilization rate of products and systems (e.g. shared accommodation, social spaces, offices or tools). Recent literature clearly highlights for the building sector the urgent need for a range of actions across the life cycle such as reduced operational and embodied impacts, as well as strategies to increase alignment of goals and action from numerous stakeholders along the value chain (Röck et al, 2020). This needs to be implemented with specific reference to people, cultures and norms in which the strategies are deployed. The pressure on the sector to embrace its role as provider of critical climate mitigation solutions, is expected to increase. There are however few explicit links to sustainable development and climate mitigation, and little common ground for the variety of analytical approaches and tools. The main aim of the CE in the literature is considered to be economic prosperity, followed by environmental quality; its impact on social equity and future generations is rarely mentioned. Circular and shared economy imply the adoption of cleaner production patterns, an increase of producers’ and consumers’ responsibility and awareness, the use of renewable technologies and materials as well as the adoption of suitable policies. It applies to different systems levels from the macro (neighborhood, city, region, nation and beyond) to the micro level (consumer, product, company). It requires the engagement of all actors in society and their capacity to create and exchange transformative patterns. In all, transition to the era of circular and shared economy aligned with climate goals requires more knowledge on the necessary changes in household’s behavior, design practices, construction and de-construction methods, business models and legal frameworks (Laurenti et al, 2019). This Virtual Special Issue (VSI) calls for new research contributions on mitigation potentials from the Circular and Sharing Economy in the buildings sector worldwide.
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| 16. |
- Novikov, Lev N, et al.
(författare)
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Exogenous brain-derived neurotrophic factor regulates the synaptic composition of axonally lesioned and normal adult rat motoneurons
- 2000
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Ingår i: Neuroscience. - : Elsevier. - 0306-4522 .- 1873-7544. ; 100:1, s. 171-181
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Tidskriftsartikel (refereegranskat)abstract
- Brain-derived neurotrophic factor has previously been shown to promote survival and axonal regeneration in injured spinal motoneurons and, also, to modulate synaptic transmission and regulate the density of synaptic innervation in a variety of neurons. The present light and electron microscopic study demonstrates synaptotrophic effects of exogenously applied brain-derived neurotrophic factor on the synaptic composition of both normal and axonally lesioned adult rat spinal motoneurons. After L5-L6 ventral root avulsion, a massive loss of all types of boutons occurred on the somata of the lesioned motoneurons which persisted for at least 12 weeks postoperatively. We found that (i) intrathecal infusion of brain-derived neurotrophic factor during the first postoperative week did not prevent the synaptic detachment and activation of glial cells; (ii) prolonged treatment for four weeks restored synaptic covering and significantly reduced microglial reaction; (iii) the synaptotrophic effect remained significant for at least eight weeks after cessation of the treatment; (iv) brain-derived neurotrophic factor mainly supported F-type boutons with presumably inhibitory function, while it had little effect on S-type boutons associated with excitatory action; and (v) in normal unlesioned motoneurons, four weeks of treatment with brain-derived neurotrophic factor induced sprouting of F-type boutons, a loss of S-type boutons and motoneuron atrophy. The present data show that exogenous neurotrophins not only help to restore synaptic circuitry in axonally injured motoneurons, but also strongly influence the synaptic composition in normal motoneurons.
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| 17. |
- Novikova, G, et al.
(författare)
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Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1610-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 40 loci associated with Alzheimer’s disease (AD), but the causal variants, regulatory elements, genes and pathways remain largely unknown, impeding a mechanistic understanding of AD pathogenesis. Previously, we showed that AD risk alleles are enriched in myeloid-specific epigenomic annotations. Here, we show that they are specifically enriched in active enhancers of monocytes, macrophages and microglia. We integrated AD GWAS with myeloid epigenomic and transcriptomic datasets using analytical approaches to link myeloid enhancer activity to target gene expression regulation and AD risk modification. We identify AD risk enhancers and nominate candidate causal genes among their likely targets (including AP4E1, AP4M1, APBB3, BIN1, MS4A4A, MS4A6A, PILRA, RABEP1, SPI1, TP53INP1, and ZYX) in twenty loci. Fine-mapping of these enhancers nominates candidate functional variants that likely modify AD risk by regulating gene expression in myeloid cells. In the MS4A locus we identified a single candidate functional variant and validated it in human induced pluripotent stem cell (hiPSC)-derived microglia and brain. Taken together, this study integrates AD GWAS with multiple myeloid genomic datasets to investigate the mechanisms of AD risk alleles and nominates candidate functional variants, regulatory elements and genes that likely modulate disease susceptibility.
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| 18. |
- Novikova, P. Y., et al.
(författare)
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Sequencing of the genus Arabidopsis identifies a complex history of nonbifurcating speciation and abundant trans-specific polymorphism
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1077-1082
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Tidskriftsartikel (refereegranskat)abstract
- The notion of species as reproductively isolated units related through a bifurcating tree implies that gene trees should generally agree with the species tree and that sister taxa should not share polymorphisms unless they diverged recently and should be equally closely related to outgroups. It is now possible to evaluate this model systematically. We sequenced multiple individuals from 27 described taxa representing the entire Arabidopsis genus. Cluster analysis identified seven groups, corresponding to described species that capture the structure of the genus. However, at the level of gene trees, only the separation of Arabidopsis thaliana from the remaining species was universally supported, and, overall, the amount of shared polymorphism demonstrated that reproductive isolation was considerably more recent than the estimated divergence times. We uncovered multiple cases of past gene flow that contradict a bifurcating species tree. Finally, we showed that the pattern of divergence differs between gene ontologies, suggesting a role for selection. © 2016 Nature America, Inc. All rights reserved.
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| 19. |
- Orekhova, Elena V, 1967, et al.
(författare)
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Auditory Cortex Responses to Clicks and Sensory Modulation Difficulties in Children with Autism Spectrum Disorders (ASD)
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH). The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD.
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| 20. |
- Orekhova, Elena V, 1967, et al.
(författare)
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Auditory Magnetic Response to Clicks in Children and Adults: Its Components, Hemispheric Lateralization and Repetition Suppression Effect
- 2013
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Ingår i: Brain Topography. - : Springer Science and Business Media LLC. - 0896-0267 .- 1573-6792. ; 26:3, s. 410-427
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Tidskriftsartikel (refereegranskat)abstract
- The auditory magnetic event-related fields (ERF) qualitatively change through the child development, reflecting maturation of auditory cortical areas. Clicks presented with long inter-stimulus interval produce distinct ERF components, and may appear useful to characterize immature EFR morphology in children. The present study is aimed to investigate morphology of the auditory ERFs in school-age children, as well as lateralization and repetition suppression of ERF components evoked by the clicks. School-age children and adults passively listened to pairs of click presented to the right ear, left ear or binaurally, with 8-11 s intervals between the pairs and a 1 s interval within a pair. Adults demonstrated a typical P50m/N100m response. Unlike adults, children had two distinct components preceding the N100m-P50m (at similar to 65 ms) and P100m (at similar to 100 ms). The P100m dominated the child ERF, and was most prominent in response to binaural stimulation. The N100m in children was less developed than in adults and partly overlapped in time with the P100m, especially in response to monaural clicks. Strong repetition suppression was observed for P50m both in children and adults, P100m in children and N100m in adults. Both children and adults demonstrated ERF amplitude and/or latency right hemispheric advantage effects that may reflect right hemisphere dominance for preattentive arousal processes. Our results contribute to the knowledge concerning development of auditory processing and its lateralization in children and have implications for investigation of the auditory evoked fields in developmental disorders.
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| 21. |
- Steg, Linda, et al.
(författare)
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A method to identify barriers to and enablers of implementing climate change mitigation options
- 2022
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Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:11, s. 1216-1227
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Forskningsöversikt (refereegranskat)abstract
- Mitigation option are not yet being implemented at the scale required to limit global warming to well below 2°C. Various factors have been identified that inhibit the implementation of specific mitigation options. Yet, an integrated assessment of key barriers and enablers is lacking. Here we present a comprehensive framework to assess which factors inhibit and enable the implementation of mitigation options. The framework comprises six dimensions, each encompassing different criteria: geophysical, environmental-ecological, technological, economic, sociocultural, and institutional feasibility. We demonstrate the approach by assessing to what extent each criterion and dimension affects the feasibility of six mitigation options. The assessment reveals that institutional factors inhibit the implementation of many options that need to be addressed to increase their feasibility. Of all the options assessed, many factors enable the implementation of solar energy, while only a few barriers would need to be addressed to implement solar energy at scale.
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