| 1. |
- Prusti, T., et al.
(author)
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The Gaia mission
- 2016
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
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Journal article (peer-reviewed)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.
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| 2. |
- Cossarizza, A., et al.
(author)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
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Journal article (peer-reviewed)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.
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| 3. |
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| 4. |
- Nene, Vishvanath, et al.
(author)
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Genome sequence of Aedes aegypti, a major arbovirus vector.
- 2007
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5832, s. 1718-23
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Journal article (peer-reviewed)abstract
- We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
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| 5. |
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| 6. |
- Lønborg, C., et al.
(author)
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A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)
- 2024
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In: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 16:2, s. 1107-1119
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Journal article (peer-reviewed)abstract
- Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) concentrations are used to characterize the dissolved organic matter (DOM) pool and are important components ofbiogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOMv1; available at https://doi.org/10.1594/PANGAEA.964012, Lønborg et al., 2023) compiling previously published and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complementedby hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables(e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon andtotal alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However,most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the SouthernHemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC,20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequenceDOC > DON > DOP, reflecting both differences in the maturity of the analytical methods and the greater focuson carbon cycling by the aquatic science community. The global database shows that the average DOC concentration in coastal waters (average ± standard deviation (SD): 182±314 µmolC L−1; median: 103 µmolC L−1) is13-fold higher than the average coastal DON concentration (13.6 ± 30.4 µmol N L−1; median: 8.0 µmol N L−1),which is itself 39-fold higher than the average coastal DOP concentration (0.34 ± 1.11 µmol P L−1; median:0.18 µmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and willhelp facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochemical processes; closing nutrient budgets; estimating carbon, nitrogen, and phosphorous pools; and establishing abaseline for modelling future changes in coastal waters.
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| 7. |
- Bjornsen, T., et al.
(author)
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High-frequency blood flow-restricted resistance exercise results in acute and prolonged cellular stress more pronounced in type I than in type II fibers
- 2021
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In: Journal of Applied Physiology. - Rockville : American Physiological Society. - 8750-7587 .- 1522-1601. ; 131:2, s. 643-660
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Journal article (peer-reviewed)abstract
- Myocellular stress with high-frequency blood flow-restricted resistance exercise (BFRRE) was investigated by measures of heat shock protein (HSP) responses, glycogen content, and inflammatory markers. Thirteen participants [age: 24 +/- 2 yr (means +/- SD), 9 males] completed two 5-day blocks of seven BFRRE sessions, separated by 10 days. Four sets of unilateral knee extensions to failure at 20% of one-repetition maximum (1RM) were performed. Muscle samples obtained before, 1 h after the first session in the first and second block (acute 1 and acute 2), after three sessions (day 4), during the "rest week," and at 3 (post 3) and 10 days postintervention (post 10) were analyzed for HSP70, alpha beta-crystallin, glycogen [periodic acid-Schiff (PAS) staining], mRNAs, miRNAs, and CD68(+) (macrophages) and CD661D(+) (neutrophils) cell numbers. alpha beta-crystallin translocated from the cytosolic to the cytoskeletal fraction after acute 1 and acute 2 (P < 0.05) and immunostaining revealed larger responses in type I than in type II fibers (acute 1, 225 +/- 184% vs. 92 +/- 81%, respectively, P = 0.001). HSP70 was increased in the cytoskeletal fraction at day 4 and post 3, and immunostaining intensities were more elevated in type I than in type II fibers at day 4 (206 +/- 84% vs. 72 +/- 112%, respectively, P <0.001), during the rest week (98 +/- 66% vs. 42 +/- 79%, P < 0.001), and at post 3 (115 +/- 82% vs. 28 +/- 78%, P = 0.003). Glycogen content was reduced in both fiber types, but most pronounced in type I, which did not recover until the rest week (-15% to 29%, P <= 0.001). Intramuscular macrophage numbers were increased by similar to 65% postintervention, but no changes were observed in muscle neutrophils. We conclude that high-frequency BFRRE with sets performed till failure stresses both fiber types, with type I fibers being most affected. NEW & NOTEWORTHY BFRRE has been reported to preferentially stress type I muscle fibers, as evidenced by HSP responses. We extend these findings by showing that the HSP responses occur in both fiber types but more so in type I fibers and that they can still be induced after a short-term training period. Furthermore, the reductions in glycogen content of type I fibers after strenuous frequent BFRRE in unaccustomed subjects can be prolonged (>= 5 days), probably due to microdamage.
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| 8. |
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| 9. |
- Li, Jian-Liang, et al.
(author)
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A genome scan for modifiers of age at onset in Huntington disease : The HD MAPS study.
- 2003
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 73:3, s. 682-7
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Journal article (peer-reviewed)abstract
- Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.
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| 10. |
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| 11. |
- Pan, W. H., et al.
(author)
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Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development
- 2018
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In: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 10
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Journal article (peer-reviewed)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.
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| 12. |
- Wortman, J. R., et al.
(author)
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The 2008 update of the Aspergillus nidulans genome annotation: A community effort
- 2009
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In: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
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Journal article (peer-reviewed)abstract
- The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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| 13. |
- Aamodt, A. H., et al.
(author)
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Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19
- 2021
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In: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 268, s. 3574-3583
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Journal article (peer-reviewed)abstract
- Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. Results In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 x 10(-7)) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02). Conclusion Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
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| 14. |
- Adde, Lars, et al.
(author)
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In-Motion-App for remote General Movement Assessment : A multi-site observational study
- 2021
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In: BMJ Open. - : BMJ. - 2044-6055. ; 11:3
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Journal article (peer-reviewed)abstract
- Objectives To determine whether videos taken by parents of their infants' spontaneous movements were in accordance with required standards in the In-Motion-App, and whether the videos could be remotely scored by a trained General Movement Assessment (GMA) observer. Additionally, to assess the feasibility of using home-based video recordings for automated tracking of spontaneous movements, and to examine parents' perceptions and experiences of taking videos in their homes. Design The study was a multi-centre prospective observational study. Setting Parents/families of high-risk infants in tertiary care follow-up programmes in Norway, Denmark and Belgium. Methods Parents/families were asked to video record their baby in accordance with the In-Motion standards which were based on published GMA criteria and criteria covering lighting and stability of smartphone. Videos were evaluated as GMA 'scorable' or 'non-scorable' based on predefined criteria. The accuracy of a 7-point body tracker software was compared with manually annotated body key points. Parents were surveyed about the In-Motion-App information and clarity. Participants The sample comprised 86 parents/families of high-risk infants. Results The 86 parent/families returned 130 videos, and 121 (96%) of them were in accordance with the requirements for GMA assessment. The 7-point body tracker software detected more than 80% of body key point positions correctly. Most families found the instructions for filming their baby easy to follow, and more than 90% reported that they did not become more worried about their child's development through using the instructions. Conclusions This study reveals that a short instructional video enabled parents to video record their infant's spontaneous movements in compliance with the standards required for remote GMA. Further, an accurate automated body point software detecting infant body landmarks in smartphone videos will facilitate clinical and research use soon. Home-based video recordings could be performed without worrying parents about their child's development. Trials registration number NCT03409978.
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| 15. |
- Bjørnsen, Thomas, et al.
(author)
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Delayed myonuclear addition, myofiber hypertrophy and increases in strength with high-frequency low-load blood flow restricted training to volitional failure.
- 2019
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In: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 126:3, s. 578-592
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Journal article (peer-reviewed)abstract
- To investigate muscle hypertrophy, strength, myonuclear and satellite cell (SC) responses to high-frequency blood flow restricted resistance exercise (BFRRE).Thirteen individuals (24±2 years [mean ± SD], 9 males) completed two 5-day-blocks of 7 BFRRE sessions, separated by a 10-day rest period. Four sets of unilateral knee extensions to voluntary failure at 20% of 1RM were conducted with partial blood flow restriction (90-100 mmHg). Muscle samples obtained before-, during, 3- and 10 days after training were analyzed for muscle fiber area (MFA), myonuclei, SC, and mRNA and miRNA expression. Muscle size was measured by ultrasonography and magnetic resonance imaging, and strength with 1RM knee-extension.With the first block of BFRRE, SC number increased in both fiber types (70-80%, p<0.05), while type I and II MFA decreased by 6±7% and 15±11% (p<0.05), respectively. With the second block of training, muscle size increased by 6-8%, while the number of SC (type I: 80±63%, type II 147±95%), myonuclei (type I: 30±24%, type II: 31±28%) and MFA (type I: 19±19%, type II: 11±19%) peaked 10 days after the second block of BFRRE, whereas strength peaked after 20 days of detraining (6±6%, p<0.05). Pax7- and p21 mRNA expression were elevated during the intervention, while myostatin, IGF1R, MyoD, myogenin, cyclinD1 and -D2 mRNA did not change until 3-10 days post intervention.High frequency low-load BFRRE induced robust increases in SC, myonuclei and muscle size, but modest strength gains. Intriguingly, the responses were delayed and peaked 10-20 days after the training intervention, indicating overreaching.
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| 16. |
- Djoussé, Luc, et al.
(author)
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Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16.
- 2004
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In: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 5:2, s. 109-14
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Journal article (peer-reviewed)abstract
- Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.
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| 17. |
- Djoussé, L, et al.
(author)
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Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease.
- 2003
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In: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 119A:3, s. 279-82
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Journal article (peer-reviewed)abstract
- Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.
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| 18. |
- Gjestvang, D., et al.
(author)
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Examination of how properties of a fissioning system impact isomeric yield ratios of the fragments
- 2023
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In: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 108:6
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Journal article (peer-reviewed)abstract
- The population of isomeric states in the prompt decay of fission fragments-so-called isomeric yield ratios (IYRs)-is known to be sensitive to the angular momentum J that the fragment emerged with, and may therefore contain valuable information on the mechanism behind the fission process. In this work, we investigate how changes in the fissioning system impact the measured IYRs of fission fragments to learn more about what parameters affect angular momentum generation. To enable this, a new technique for measuring IYRs is first demonstrated. It is based on the time of arrival of discrete gamma rays, and has the advantage that it enables the study of the IYR as a function of properties of the partner nucleus. This technique is used to extract the IYR of 134Te, strongly populated in actinide fission, from the three different fissioning systems: 232Th(n, f), 238U(n, f), at two different neutron energies, as well as 252Cf(sf). The impacts of changing the fissioning system, the compound nuclear excitation energy, the minimum J of the binary partner, and the number of neutrons emitted on the IYR of 134Te are determined. The decay code TALYS is used in combination with the fission simulation code FREYA to calculate the primary fragment angular momentum from the IYR. We find that the IYR of 134Te has a slope of 0.004 +/- 0.002 with increase in compound nucleus (CN) mass. When investigating the impact on the IYR of increased CN excitation energy, we find no change with an energy increase similar to the difference between thermal and fast fission. By varying the mass of the partner fragment emerging with 134Te, it is revealed that the IYR of 134Te is independent of the total amount of prompt neutrons emitted from the fragment pair. This indicates that neutrons carry minimal angular momentum away from the fission fragments. Comparisons with the FREYA+TALYS simulations reveal that the average angular momentum in 134Te following 238U(n, f) is 6.0 h over bar . This is not consistent with the value deduced from recent CGMF calculations. Finally, the IYR sensitivity to the angular momentum of the primary fragment is discussed. These results are not only important to help understanding the underlying mechanism in nuclear fission, but can also be used to constrain and benchmark fission models, and are relevant to the gamma -ray heating problem of reactors.
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| 19. |
- Knudtzen, F. C., et al.
(author)
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Lyme neuroborreliosis with encephalitis; a systematic literature review and a Scandinavian cohort study
- 2022
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In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X. ; 28:5, s. 649-656
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Journal article (peer-reviewed)abstract
- Background: Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described. Objectives: To describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study. Data sources: Medline, Embase, Scopus, Cochrane library. Study eligibility criteria: There was no discrimination on study type, time of publication or language. Participants: Review: All articles with definite LNB and confirmed/possible encephalitis. Cohort: LNB cohorts from Denmark, Sweden and Norway 1990–2019 were screened for patients with encephalitis. Methods: Review: Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies. Cohort: Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered. Results: Review: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2–90 days). Of 38 patients with available follow-up after median 12 months (IQR 5–13), 32 had fully or partially recovered, two had died. Cohort: Thirty-five patients (median age 67 years, IQR 48–76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2–4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7–34), with further 7 days (IQR 3–34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113–389), 65.6% had residual symptoms. None had died. Conclusions: This study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi-endemic areas should be considered. © 2021 The Author(s)
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| 20. |
- Paulsen, B. S., et al.
(author)
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Ectopic expression of RAD52 and dn53BP1 improves homology-directed repair during CRISPR-Cas9 genome editing
- 2017
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In: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 1:11, s. 878-888
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Journal article (peer-reviewed)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).
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| 21. |
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| 22. |
- Sachdev, P.S., et al.
(author)
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Diagnostic criteria for vascular cognitive disorders: A VASCOG statement
- 2014
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In: Alzheimer Disease and Associated Disorders. - 0893-0341. ; 28:3, s. 206-218
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Journal article (peer-reviewed)abstract
- BACKGROUND:: Several sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination. METHODS:: Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the fifth revision of Diagnostic and Statistical Manual (DSM-5) Task Force. RESULTS:: Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent cooccurrence of Alzheimer disease pathology emphasized. CONCLUSIONS:: The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved. © 2014 by Lippincott Williams and Wilkins.
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| 23. |
- Schwensen, Jakob F., et al.
(author)
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The epidemic of methylisothiazolinone : A European prospective study
- 2017
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In: Contact Dermatitis. - : Wiley. - 0105-1873. ; 76:5, s. 272-279
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Journal article (peer-reviewed)abstract
- Background: The use of methylisothiazolinone (MI) in cosmetic products has caused an unprecedented epidemic of MI contact allergy. Current data concerning exposures at a European level are required. Objectives: To describe demographics and MI exposures for European patients with MI contact allergy. Methods: Eleven European dermatology departments from eight European countries prospectively collected data between 1 May and 31 October 2015 among consecutive patients who had positive patch test reactions to MI (2000ppm aq.). Results: A total of 6.0% (205/3434; range 2.6-13.0%) of patients had positive patch test reactions to MI. Dermatitis most frequently affected the hands (43.4%), face (32.7%), arms (14.6%), and eyelids (11.7%); 12.7% had widespread dermatitis. For 72.7% (149/205), MI contact allergy was currently relevant mainly because of exposure to cosmetic products (83.2%; 124/149). Of these 124 patients, 19.5% were exposed to leave-on and rinse-off cosmetic products, 24.8% only to leave-on cosmetic products and 38.9% only to rinse-off cosmetic products containing MI or methylchloroisothiazolinone/MI. The majority of these (79%) noted onset of their dermatitis between 2013 and 2015. Fifteen patients (7.3%) had previously experienced allergic reactions when they were in newly painted rooms. Conclusion: Clinically relevant MI contact allergy remains prevalent across European countries, mainly because of exposure to rinse-off and leave-on cosmetic products.
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- Wichert, R., et al.
(author)
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Mucus Detachment by Host Metalloprotease Meprin beta Requires Shedding of Its Inactive Pro-form, which Is Abrogated by the Pathogenic Protease RgpB
- 2017
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 21:8, s. 2090-2103
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Journal article (peer-reviewed)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.
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