Background & AimsConstitutional mismatch repair deficiency (CMMRD) is a rare recessive childhood cancer predisposition syndrome caused by germline mismatch repair variants. Constitutional microsate...Show moreBackground & AimsConstitutional mismatch repair deficiency (CMMRD) is a rare recessive childhood cancer predisposition syndrome caused by germline mismatch repair variants. Constitutional microsatellite instability (cMSI) is a CMMRD diagnostic hallmark and may associate with cancer risk. We quantified cMSI in a large CMMRD patient cohort to explore genotype–phenotype correlations using novel MSI markers selected for instability in blood.MethodsThree CMMRD, 1 Lynch syndrome, and 2 control blood samples were genome sequenced to >120× depth. A pilot cohort of 8 CMMRD and 38 control blood samples and a blinded cohort of 56 CMMRD, 8 suspected CMMRD, 40 Lynch syndrome, and 43 control blood samples were amplicon sequenced to 5000× depth. Sample cMSI score was calculated using a published method comparing microsatellite reference allele frequencies with 80 controls.ResultsThirty-two mononucleotide repeats were selected from blood genome and pilot amplicon sequencing data. cMSI scoring using these MSI markers achieved 100% sensitivity (95% CI, 93.6%–100.0%) and specificity (95% CI 97.9%–100.0%), was reproducible, and was superior to an established tumor MSI marker panel. Lower cMSI scores were found in patients with CMMRD with MSH6 deficiency and patients with at least 1 mismatch repair missense variant, and patients with biallelic truncating/copy number variants had higher scores. cMSI score did not correlate with age at first tumor.ConclusionsWe present an inexpensive and scalable cMSI assay that enhances CMMRD detection relative to existing methods. cMSI score is associated with mismatch repair genotype but not phenotype, suggesting it is not a useful predictor of cancer risk. Show less
Pan, K.; Marshall, L.; Biesmeijer, J.C.; Snoo G.R. de 2022
Plants can be pollinated in many ways, with insect, wind and selfingas the most common modes. While it seems likely that the occurrence of pollination modes is correlated with environmental... Show morePlants can be pollinated in many ways, with insect, wind and selfingas the most common modes. While it seems likely that the occurrence of pollination modes is correlated with environmental conditions, e.g. vegetation structure, and this remains uncertain. Here, we mapped the composition of pollination modes of different plant groups (woody species, herbs,and grasses) across (semi-)natural habitats and their distributions in relation to 3D vegetation structure in the Netherlands. We found insect pollination is the most common mode across (semi-)natural habitats for woody species and herbs. Woody species pollinated by insects showed an even higher percentage in dune, river swamp and swamp peat than in other habitat types, whereas herbs showed a higher percentage of insect pollination in dune than in other habitat types. Grasses were always pollinated by wind or wind-self in all habitats. Woody plants pollinated by wind showed a positive relationship with canopy densities in three different strata from 2 to 20 m vegetation, while insect pollination showed a positive relationship with the canopy density of 0.5 to 2 m vegetation. All grass presented negative relationships with canopy density. Herbs showed different relationships with canopy densities of different strata dependent on pollination modes. Insect-pollinated species increased with canopy densities of low strata but decreased with canopy density of high strata, whereas wind-pollinated species decreased with canopy density of both low and high strata. We conclude that habitat and vegetation structure are important factors driving the distribution of pollination modes. Show less
Pan, K.; Moens, M.; Marshall, L.; Cieraad, E.; Biesmeijer, K.; Snoo, G.R. de 2021
In a warming climate, species are expected to shift their geographical ranges to higher elevations and latitudes, and if interacting species shift at different rates, networks may be disrupted. To... Show moreIn a warming climate, species are expected to shift their geographical ranges to higher elevations and latitudes, and if interacting species shift at different rates, networks may be disrupted. To quantify the effects of ongoing climate change, repeating historical biodiversity surveys is necessary. In this study, we compare the distribution of a plant-pollinator community between two surveys 115 years apart (1889 and 2005-06), reporting distribution patterns and changes observed for bumblebee species and bumblebee-visited plants in the Gavarnie-Gedre commune in the Pyrenees, located in southwest Europe at the French-Spanish border. The region has warmed significantly over this period, alongside shifts in agricultural land use and forest. The composition of the bumblebee community shows relative stability, but we observed clear shifts to higher elevations for bumblebees (averaging 129 m) and plants (229 m) and provide preliminary evidence that some bumblebee species shift with the plants they visit. We also observe that some species have been able to occupy the same climate range in both periods by shifting elevation range. The results suggest the need for long-term monitoring to determine the role and impact of the different drivers of global change, especially in montane habitats where the impacts of climate changes are anticipated to be more extreme. Show less
Tanis, M.F.; Marshall, L.; Biesmeijer, J.C.; Kolfschoten, L. van 2020
Agricultural intensification and loss of semi-natural grassland have contributed to biodiversity decline, including pollinator species, in pastures around the world. To reverse the decline, agri... Show moreAgricultural intensification and loss of semi-natural grassland have contributed to biodiversity decline, including pollinator species, in pastures around the world. To reverse the decline, agri-environmental schemes have been implemented, varying widely in effectiveness. In addition, many countries, including the Netherlands, have established nature reserves in which semi-natural grasslands are restored and are often managed for specific groups of species, e.g. meadow birds or plants. The effects of such measures on insect biodiversity are not well known but recent reports on the dramatic decline of insect biomass in nature reserves have put even more attention to the impact of land use and management on biodiversity. This study compares pollinator abundance and species richness in three common semi-natural grassland management types in the Netherlands: (1) hay meadows, (2) herb-rich grasslands and (3) meadow bird grasslands. Pollinator abundance and species richness were assessed in eleven study areas, each with all three management types present. Standardized transects, insect sampling within a standard 20 min time frame and plot-based flower surveys were used in spring and summer to assess the relationships between management regime, floral abundance and diversity and pollinator communities. The results show that meadow bird grasslands have lower pollinator abundance and diversity and a less unique pollinator assemblage than both other types. Moreover, flower abundance has a positive effect on pollinator abundance and flower diversity has a positive effect on pollinator species richness. These results indicate that meadow-bird grasslands are a comparatively unfavourable habitat for bees, hoverflies and butterflies, which may be explained by a lack of flowers as well as unsuitable mowing practices. Measures benefitting both insectivorous birds and flower-visiting insects, such as rotational mowing, could remediate this imbalance. (C) 2019 The Authors. Published by Elsevier GmbH on behalf of Gesellschaft fur Okologie. Show less
Dougados, M.; Heijde, D. van der; Tsai, W.C.; Saaibi, D.; Marshall, L.; Jones, H.; ... ; Tarallo, M. 2020
Background We assessed the external validity of composite indices Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Assessment... Show moreBackground We assessed the external validity of composite indices Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Assessment in SpondyloArthritis international Society (ASAS) 40 response (ASAS40) by evaluating the correlations between the changes in some patient reported outcomes (PROs) for patients with non-radiographic axial spondyloarthritis (nr-axSpA) and the changes in the scores of the composite indices. Methods This was a post-hoc analysis of data from the EMBARK study in patients with nr-axSpA treated with etanercept. PROs were grouped according to ASDAS status (inactive [< 1.3], low [>= 1.3 to < 2.1], high [>= 2.1 to <= 3.5], and very high [> 3.5]), patient achievement of > 50% improvement in BASDAI (BASDAI50 responders), and > 40% improvement in ASAS (ASAS40 responders) at 104 weeks. Analyses were conducted on observed cases available at Week 104. Changes in PROs from Baseline to Week 104 were assessed using analysis of covariance with adjustment for baseline with linear contrast. Results Higher ASDAS disease activity at 104 weeks was associated with lower long-term improvement from baseline in PROs (e.g., total back pain [visual analog scale, cm (95% confidence interval): - 4.58 (- 4.95, - 4.21), - 3.86 (- 4.28, - 3.43), - 2.15 (- 2.68, - 1.61), and 1.30 (- 0.51, 3.12) for inactive, low, high, and very high ASDAS disease activity, respectively; Multidimensional Fatigue Inventory (MFI) general fatigue: - 4.77 (- 5.70, - 3.84), - 2.96 (- 4.04, - 1.87), - 1.00 (- 2.32, 0.31), and 2.14 (- 2.10, 6.38); all p < 0.001)]. BASDAI50 non-responders had less improvement in PROs from Baseline to Week 104 vs. responders (e.g., total back pain: - 1.61 (- 2.05, - 1.18) vs. -4.43 (- 4.69, - 4.18); MFI general fatigue: - 0.01 (- 1.12, 1.09) vs. -4.30 (- 4.98, - 3.62); all p < 0.001). ASAS40 non-responders also had less improvement in PROs from Baseline to Week 104 vs. responders (e.g., total back pain: - 1.91 (- 2.30, - 1.52) vs. -4.75 (- 5.05, - 4.46); MFI general fatigue: - 0.63 (- 1.56, 0.30) vs. -4.64 (- 5.37, - 3.91); all p < 0.001). Conclusion Composite indices are valid for monitoring treatment response and adequately reflect treatment-related changes experienced by patients with nr-axSpA. Show less
Maksymowych, W.P.; Claudepierre, P.; Hooge, M. de; Lambert, R.G.; Landewe, R.B.M.; Molto, A.; ... ; Dougados, M. 2017