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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Hu, H., et al.
(författare)
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X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:1, s. 133-148
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Tidskriftsartikel (refereegranskat)abstract
- X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.
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- Reeves, Jessica M., et al.
(författare)
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Palaeoenvironmental change in tropical Australasia over the last 30,000 years - a synthesis by the OZ-INTIMATE group
- 2013
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 74, s. 97-114
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Tidskriftsartikel (refereegranskat)abstract
- The tropics are the major source of heat and moisture for the Australasian region. Determining the tropics' response over time to changes in climate forcing mechanisms, such as summer insolation, and the effects of relative sea level on exposed continental shelves during the Last Glacial period, is an ongoing process of re-evaluation. We present a synthesis of climate proxy data from tropical Australasia spanning the last 30,000 years that incorporates deep sea core, coral, speleothem, pollen, charcoal and terrestrial sedimentary records. Today, seasonal variability is governed largely by the annual migration of the inter-tropical convergence zone (ITCZ), influencing this region most strongly during the austral summer. However, the position of the ITCZ has varied through time. Towards the end of Marine Isotope Stage (MIS) 3, conditions were far wetter throughout the region, becoming drier first in the south. Universally cooler land and sea-surface temperature (SST) were characteristic of the Last Glacial Maximum, with drier conditions than previously, although episodic wet periods are noted in the fluvial records of northern Australia. The deglacial period saw warming first in the Coral Sea and then the Indonesian seas, with a pause in this trend around the time of the Antarctic Cold Reversal (c. 14.5 ka), coincident with the flooding of the Sunda Shelf. Wetter conditions occurred first in Indonesia around 17 ka and northern Australia after 14 ka. The early Holocene saw a peak in marine SST to the northwest and northeast of Australia. Modern vegetation was first established on Indonesia, then progressively south and eastward to NE Australia. Flores and the Atherton Tablelands show a dry period around 11.6 ka, steadily becoming wetter through the early Holocene. The mid-late Holocene was punctuated by millennial-scale variability, associated with the El Nino-Southern Oscillation; this is evident in the marine, coral, speleothem and pollen records of the region.
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| 8. |
- Reynaert, N, et al.
(författare)
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Short Stature in KBG Syndrome: First Responses to Growth Hormone Treatment
- 2015
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 83:5, s. 361-364
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> KBG syndrome is a rare disorder characterized by intellectual disability and associated with macrodontia of the upper central incisors, specific craniofacial findings, short stature and skeletal anomalies. Genetic corroboration of a clinical diagnosis has been possible since 2011, upon identification of heterozygous mutations in or a deletion of the <i>ANKRD11</i> gene. <b><i>Methods:</i></b> We summarized the height data of 14 adults and 18 children (age range 2-16 years) with a genetically confirmed diagnosis of KBG syndrome. Two of these children were treated with growth hormones. <b><i>Results:</i></b> Stature below the 3rd centile or -1.88 standard deviation score (SDS) was observed in 72% of KBG children and in 57% of KBG adults. Height below -2.50 SDS was observed in 62% of KBG children and in 36% of KBG adults. The mean SDS of height in KBG children was -2.56 and in KBG adults -2.17. Two KBG children on growth hormone therapy increased their height by 0.6 and 1 SDS within 1 year, respectively. The former also received a gonadotropin-releasing hormone agonist due to medical necessity. <b><i>Conclusion:</i></b> Short stature is prevalent in KBG syndrome, and spontaneous catch-up growth beyond childhood appears limited. Growth hormone intervention in short KBG children is perceived as promising.
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- Uddin, M, et al.
(författare)
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Indexing Effects of Copy Number Variation on Genes Involved in Developmental Delay
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28663-
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Tidskriftsartikel (refereegranskat)abstract
- A challenge in clinical genomics is to predict whether copy number variation (CNV) affecting a gene or multiple genes will manifest as disease. Increasing recognition of gene dosage effects in neurodevelopmental disorders prompted us to develop a computational approach based on critical-exon (highly expressed in brain, highly conserved) examination for potential etiologic effects. Using a large CNV dataset, our updated analyses revealed significant (P < 1.64 × 10−15) enrichment of critical-exons within rare CNVs in cases compared to controls. Separately, we used a weighted gene co-expression network analysis (WGCNA) to construct an unbiased protein module from prenatal and adult tissues and found it significantly enriched for critical exons in prenatal (P < 1.15 × 10−50, OR = 2.11) and adult (P < 6.03 × 10−18, OR = 1.55) tissues. WGCNA yielded 1,206 proteins for which we prioritized the corresponding genes as likely to have a role in neurodevelopmental disorders. We compared the gene lists obtained from critical-exon and WGCNA analysis and found 438 candidate genes associated with CNVs annotated as pathogenic, or as variants of uncertain significance (VOUS), from among 10,619 developmental delay cases. We identified genes containing CNVs previously considered to be VOUS to be new candidate genes for neurodevelopmental disorders (GIT1, MVB12B and PPP1R9A) demonstrating the utility of this strategy to index the clinical effects of CNVs.
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- Cox, E., et al.
(författare)
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The Intriguing Interaction of Escherichia coli with the Host Environment and Innovative Strategies To Interfere with Colonization: a Summary of the 2019 E. coli and the Mucosal Immune System Meeting
- 2020
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Ingår i: Applied and environmental microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 86:24
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The third E. coli and the Mucosal Immune System (ECMIS) meeting was held at Ghent University in Belgium from 2 to 5 June 2019. It brought together an international group of scientists interested in mechanisms of colonization, host response, and vaccine development. ECMIS distinguishes itself from related meetings on these enteropathogens by providing a greater emphasis on animal health and disease and covering a broad range of pathotypes, including enterohemorrhagic, enteropathogenic, enterotoxigenic, enteroaggregative, and extraintestinal pathogenic Escherichia coli. As it is well established that the genus Shigella represents a subspecies of E. coli, these organisms along with related enteroinvasive E. coli are also included. In addition, Tannerella forsythia, a periodontal pathogen, was presented as an example of a pathogen which uses its surface glycans for mucosal interaction. This review summarizes several highlights from the 2019 meeting and major advances to our understanding of the biology of these pathogens and their impact on the host.
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- Kraljic, Katarina, et al.
(författare)
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Emergence and cosmic evolution of the Kennicutt- Schmidt relation driven by interstellar turbulence
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361. ; 682
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Tidskriftsartikel (refereegranskat)abstract
- The scaling relations between the gas content and star formation rate of galaxies provide useful insights into the processes governing their formation and evolution. We investigated the emergence and the physical drivers of the global Kennicutt-Schmidt (KS) relation at 0:25 ≤ z ≤ 4 in the cosmological hydrodynamic simulation NewHorizon, capturing the evolution of a few hundred galaxies with a resolution down to 34 pc. The details of this relation vary strongly with the stellar mass of galaxies and the redshift. A power-law relation ΣSFR / Σa gas with a ≈ 1:4, like that found empirically, emerges at z ≈ 2..3 for the more massive half of the galaxy population. However, no such convergence is found in the lower-mass galaxies, for which the relation gets shallower with decreasing redshift. At galactic scales, the star formation activity correlates with the level of turbulence of the interstellar medium, quantified by the Mach number, rather than with the gas fraction (neutral or molecular), confirming the conclusions found in previous works. With decreasing redshift, the number of outliers with short depletion times diminishes, reducing the scatter of the KS relation, while the overall population of galaxies shifts toward low densities. Our results, from parsec-scale star formation models calibrated with local Universe physics, demonstrate that the cosmological evolution of the environmental (e.g., mergers) and internal conditions (e.g., gas fractions) conspire to shape the KS relation. This is an illustration of how the interplay of global and local processes leaves a detectable imprint on galactic-scale observables and scaling relations.
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| 15. |
- Pierre, M., et al.
(författare)
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The XXL survey : First results and future
- 2017
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Ingår i: Astronomical Notes - Astronomische Nachrichten. - : Wiley-VCH Verlagsgesellschaft. - 0004-6337 .- 1521-3994. ; 338:2-3, s. 334-341
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Tidskriftsartikel (refereegranskat)abstract
- The XXL survey currently covers two 25 deg(2) patches with XMM observations of similar to 10 ks. We summarize the scientific results associated with the first release of the XXL dataset, which occurred in mid-2016. We review several arguments for increasing the survey depth to 40 ks during the next decade of XMM operations. X-ray (z < 2) cluster, (z < 4) active galactic nuclei (AGN), and cosmic background survey science will then benefit from an extraordinary data reservoir. This, combined with deep multi-lambda observations, will lead to solid standalone cosmological constraints and provide a wealth of information on the formation and evolution of AGN, clusters, and the X-ray background. In particular, it will offer a unique opportunity to pinpoint the z > 1 cluster density. It will eventually constitute a reference study and an ideal calibration field for the upcoming eROSITA and Euclid missions.
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| 16. |
- Pierre, M., et al.
(författare)
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The XXL Survey I. Scientific motivations - XMM-Newton observing plan - Follow-up observations and simulation programme
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592
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Tidskriftsartikel (refereegranskat)abstract
- Context. The quest for the cosmological parameters that describe our universe continues to motivate the scientific community to undertake very large survey initiatives across the electromagnetic spectrum. Over the past two decades, the Chandra and XMM-Newton observatories have supported numerous studies of X-ray-selected clusters of galaxies, active galactic nuclei (AGNs), and the X-ray background. The present paper is the first in a series reporting results of the XXL-XMM survey; it comes at a time when the Planck mission results are being finalised. Aims. We present the XXL Survey, the largest XMM programme totaling some 6.9 Ms to date and involving an international consortium of roughly 100 members. The XXL Survey covers two extragalactic areas of 25 deg(2) each at a point-source sensitivity of similar to 5 x 10(-15) erg s(-1) cm(-2) in the [0.5-2] keV band (completeness limit). The survey's main goals are to provide constraints on the dark energy equation of state from the space-time distribution of clusters of galaxies and to serve as a pathfinder for future, wide-area X-ray missions. We review science objectives, including cluster studies, AGN evolution, and large-scale structure, that are being conducted with the support of approximately 30 follow-up programmes. Methods. We describe the 542 XMM observations along with the associated multi-lambda and numerical simulation programmes. We give a detailed account of the X-ray processing steps and describe innovative tools being developed for the cosmological analysis. Results. The paper provides a thorough evaluation of the X-ray data, including quality controls, photon statistics, exposure and background maps, and sky coverage. Source catalogue construction and multi-lambda associations are briefly described. This material will be the basis for the calculation of the cluster and AGN selection functions, critical elements of the cosmological and science analyses. Conclusions. The XXL multi-lambda data set will have a unique lasting legacy value for cosmological and extragalactic studies and will serve as a calibration resource for future dark energy studies with clusters and other X-ray selected sources. With the present article, we release the XMM XXL photon and smoothed images along with the corresponding exposure maps.
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| 17. |
- Vandevijvere, Stefanie, et al.
(författare)
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Evaluation of food and nutrient intake assessment using concentration biomarkers in European adolescents from the HELENA study
- 2013
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 109:4, s. 736-747
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Tidskriftsartikel (refereegranskat)abstract
- Accurate food and nutrient intake assessment is essential for investigating diet-disease relationships. In the present study, food and nutrient intake assessment among European adolescents using 24 h recalls (mean of two recalls) and a FFQ (separately and the combination of both) were evaluated using concentration biomarkers. Biomarkers included were vitamin C, β-carotene, DHA+EPA, vitamin B12 (cobalamin and holo-transcobalamin) and folate (erythrocyte folate and plasma folate). For the evaluation of the food intake assessment 390 adolescents were included, while 697 were included for the nutrient intake assessment evaluation. Spearman rank and Pearson correlations, and validity coefficients, which are correlations between intake estimated and habitual true intake, were calculated. Correlations were higher between frequency of food consumption (from the FFQ) and concentration biomarkers than between mean food intake (from the recalls) and concentration biomarkers, especially for DHA+EPA (r 0·35 v. r 0·27). Most correlations were higher among girls than boys. For boys, the highest validity coefficients were found for frequency of fruit consumption (0·88) and for DHA+EPA biomarker (0·71). In girls, the highest validity coefficients were found for fruit consumption frequency (0·76), vegetable consumption frequency (0·74), mean fruit intake (0·90) and DHA+EPA biomarker (0·69). After exclusion of underreporters, correlations slightly improved. Correlations between usual food intakes, adjusted for food consumption frequency, and concentration biomarkers were higher than correlations between mean food intakes and concentration biomarkers. In conclusion, two non-consecutive 24 h recalls in combination with a FFQ seem to be appropriate to rank subjects according to their usual food intake
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| 18. |
- Vyncke, K, et al.
(författare)
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Validation of the Diet Quality Index for Adolescents by comparison with biomarkers, nutrient and food intakes : the HELENA study
- 2013
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 109:11, s. 2067-2078
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Tidskriftsartikel (refereegranskat)abstract
- Food-based dietary guidelines (FBDG) aim to address the nutritional requirements at population level in order to prevent diseases and promote a healthy lifestyle. Diet quality indices can be used to assess the compliance with these FBDG. The present study aimed to investigate whether the newly developed Diet Quality Index for Adolescents (DQI-A) is a good surrogate measure for adherence to FBDG, and whether adherence to these FBDG effectively leads to better nutrient intakes and nutritional biomarkers in adolescents. Participants included 1804 European adolescents who were recruited in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study. Dietary intake was assessed by two, non-consecutive 24 h recalls. A DQI-A score, considering the components' dietary quality, diversity and equilibrium, was calculated. Associations between the DQI-A and food and nutrient intakes and blood concentration biomarkers were investigated using multilevel regression analysis corrected for centre, age and sex. DQI-A scores were associated with food intake in the expected direction: positive associations with nutrient-dense food items, such as fruits and vegetables, and inverse associations with energy-dense and low-nutritious foods. On the nutrient level, the DQI-A was positively related to the intake of water, fibre and most minerals and vitamins. No association was found between the DQI-A and total fat intake. Furthermore, a positive association was observed with 25-hydroxyvitamin D, holo-transcobalamin and n-3 fatty acid serum levels. The present study has shown good validity of the DQI-A by confirming the expected associations with food and nutrient intakes and some biomarkers in blood.
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