| 1. |
|
|
| 2. |
- Prusti, T., et al.
(författare)
-
The Gaia mission
- 2016
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
-
Tidskriftsartikel (refereegranskat)abstract
- Gaia is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.
|
|
| 3. |
- Cossarizza, A., et al.
(författare)
-
Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
-
Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
-
Tidskriftsartikel (refereegranskat)abstract
- These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
|
|
| 4. |
- Pan, W. H., et al.
(författare)
-
Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development
- 2018
-
Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The interplay of epigenetic processes and the intestinal microbiota may play an important role in intestinal development and homeostasis. Previous studies have established that the microbiota regulates a large proportion of the intestinal epithelial transcriptome in the adult host, but microbial effects on DNA methylation and gene expression during early postnatal development are still poorly understood. Here, we sought to investigate the microbial effects on DNA methylation and the transcriptome of intestinal epithelial cells (IECs) during postnatal development. Methods: We collected IECs from the small intestine of each of five 1-, 4-and 12 to 16-week-old mice representing the infant, juvenile, and adult states, raised either in the presence or absence of a microbiota. The DNA methylation profile was determined using reduced representation bisulfite sequencing (RRBS) and the epithelial transcriptome by RNA sequencing using paired samples from each individual mouse to analyze the link between microbiota, gene expression, and DNA methylation. Results: We found that microbiota-dependent and -independent processes act together to shape the postnatal development of the transcriptome and DNA methylation signatures of IECs. The bacterial effect on the transcriptome increased over time, whereas most microbiota-dependent DNA methylation differences were detected already early after birth. Microbiota-responsive transcripts could be attributed to stage-specific cellular programs during postnatal development and regulated gene sets involved primarily immune pathways and metabolic processes. Integrated analysis of the methylome and transcriptome data identified 126 genomic loci at which coupled differential DNA methylation and RNA transcription were associated with the presence of intestinal microbiota. We validated a subset of differentially expressed and methylated genes in an independent mouse cohort, indicating the existence of microbiota-dependent " functional" methylation sites which may impact on long-term gene expression signatures in IECs. Conclusions: Our study represents the first genome-wide analysis of microbiota-mediated effects on maturation of DNA methylation signatures and the transcriptional program of IECs after birth. It indicates that the gut microbiota dynamically modulates large portions of the epithelial transcriptome during postnatal development, but targets only a subset of microbially responsive genes through their DNA methylation status.
|
|
| 5. |
- Wichert, R., et al.
(författare)
-
Mucus Detachment by Host Metalloprotease Meprin beta Requires Shedding of Its Inactive Pro-form, which Is Abrogated by the Pathogenic Protease RgpB
- 2017
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 21:8, s. 2090-2103
-
Tidskriftsartikel (refereegranskat)abstract
- The host metalloprotease meprin beta is required for mucin 2 (MUC2) cleavage, which drives intestinal mucus detachment and prevents bacterial over-growth. To gain access to the cleavage site in MUC2, meprin b must be proteolytically shed from epithelial cells. Hence, regulation of meprin b shedding and activation is important for physiological and pathophysiological conditions. Here, we demonstrate that meprin b activation and shedding are mutually exclusive events. Employing ex vivo small intestinal organoid and cell culture experiments, we found that ADAM-mediated shedding is restricted to the inactive pro-form of meprin beta and is completely inhibited upon its conversion to the active form at the cell surface. This strict regulation of meprin beta activity can be overridden by pathogens, as demonstrated for the bacterial protease Arg-gingipain (RgpB). This secreted cysteine protease potently converts membrane-bound meprin beta into its active form, impairing meprin beta shedding and its function as a mucus-detaching protease.
|
|
| 6. |
- Giblin, S. R., et al.
(författare)
-
Pauling Entropy, Metastability, and Equilibrium in Dy2Ti2O7 Spin Ice
- 2018
-
Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 121:6
-
Tidskriftsartikel (refereegranskat)abstract
- Determining the fate of the Pauling entropy in the classical spin ice material Dy2Ti2O7 with respect to the third law of thermodynamics has become an important test case for understanding the existence and stability of ice-rule states in general. The standard model of spin ice-the dipolar spin ice model-predicts an ordering transition at T approximate to 0.15 K, but recent experiments by Pomaranski et al. suggest an entropy recovery over long timescales at temperatures as high as 0.5 K, much too high to be compatible with the theory. Using neutron scattering and specific heat measurements at low temperatures and with long timescales ( 0.35 K/10(6) s and 0.5 K/10(5) s, respectively) on several isotopically enriched samples, we find no evidence of a reduction of ice-rule correlations or spin entropy. High-resolution simulations of the neutron structure factor show that the spin correlations remain well described by the dipolar spin ice model at all temperatures. Furthermore, by careful consideration of hyperfine contributions, we conclude that the original entropy measurements of Ramirez et al. are, after all, essentially correct: The short-time relaxation method used in that study gives a reasonably accurate estimate of the equilibrium spin ice entropy due to a cancellation of contributions.
|
|
| 7. |
- Landsverk, Ole J. B., et al.
(författare)
-
Antibody-secreting plasma cells persist for decades in human intestine
- 2017
-
Ingår i: Journal of Experimental Medicine. - NewYork, USA : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 214:2, s. 309-317
-
Tidskriftsartikel (refereegranskat)abstract
- Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, PCs in the gut have been considered short lived. In this study, we studied PC dynamics in the human small intestine by cell-turnover analysis in organ transplants and by retrospective cell birth dating measuring carbon-14 in genomic DNA. We identified three distinct PC subsets: a CD19(+) PC subset was dynamically exchanged, whereas of two CD19(-) PC subsets, CD45(+) PCs exhibited little and CD45(-) PCs no replacement and had a median age of 11 and 22 yr, respectively. Accumulation of CD45(-) PCs during ageing and the presence of rotavirus-specific clones entirely within the CD19(-) PC subsets support selection and maintenance of protective PCs for life in human intestine.
|
|
| 8. |
- Meaney, Paul M, 1960, et al.
(författare)
-
Electrical Characterization of Glycerin: Water Mixtures: Implications for Use as a Coupling Medium in Microwave Tomography
- 2017
-
Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480 .- 1557-9670. ; 65:5, s. 1471-1478
-
Tidskriftsartikel (refereegranskat)abstract
- We examine the broadband behavior of complex electrical properties of glycerin and water mixtures over the frequency range of 0.1-25.0 GHz, especially as they relate to using these liquids as coupling media for microwave tomographic imaging. Their combination is unique in that they are mutually miscible over the full range of concentrations, which allows them to be tailored to dielectric property matching for biological tissues. While the resultant mixture properties are partially driven by differences in the inherent low-frequency permittivity of each constituent, relaxation frequency shifts play a disproportionately larger role in increasing the permittivity dispersion while also dramatically increasing the effective conductivity over the frequency range of 1-3 GHz. For the full range of mixture ratios, the relaxation frequency shifts from 17.5 GHz for 0% glycerin to less than 0.1 GHz for 100% glycerin. Of particular interest is the fact that the conductivity stays above 1.0 S/m over the 1-3-GHz range for glycerin mixture ratios (70%-90% glycerin) we use for microwave breast tomography. The high level of attenuation is critical for suppressing unwanted multipath signals. This paper presents a full characterization of these liquids along with a discussion of their benefits and limitations in the context of microwave tomography.
|
|
| 9. |
- Paulsen, B. S., et al.
(författare)
-
Ectopic expression of RAD52 and dn53BP1 improves homology-directed repair during CRISPR-Cas9 genome editing
- 2017
-
Ingår i: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 1:11, s. 878-888
-
Tidskriftsartikel (refereegranskat)abstract
- Gene disruption by clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) is highly efficient and relies on the error-prone non-homologous end-joining pathway. Conversely, precise gene editing requires homology-directed repair (HDR), which occurs at a lower frequency than non-homologous end-joining in mammalian cells. Here, by testing whether manipulation of DNA repair factors improves HDR efficacy, we show that transient ectopic co-expression of RAD52 and a dominant-negative form of tumour protein p53-binding protein 1 (dn53BP1) synergize to enable efficient HDR using a single-stranded oligonucleotide DNA donor template at multiple loci in human cells, including patient-derived induced pluripotent stem cells. Co-expression of RAD52 and dn53BP1 improves multiplexed HDR-mediated editing, whereas expression of RAD52 alone enhances HDR with Cas9 nickase. Our data show that the frequency of non-homologous end-joining-mediated double-strand break repair in the presence of these two factors is not suppressed and suggest that dn53BP1 competitively antagonizes 53BP1 to augment HDR in combination with RAD52. Importantly, co-expression of RAD52 and dn53BP1 does not alter Cas9 off-target activity. These findings support the use of RAD52 and dn53BP1 co-expression to overcome bottlenecks that limit HDR in precision genome editing. © 2017 The Author(s).
|
|
| 10. |
|
|
