| 1. |
- Paschinger, K., et al.
(författare)
-
N-glycan antennal modifications are altered in Caenorhabditis elegans lacking the HEX-4 N-acetylgalactosamine-specific hexosaminidase
- 2023
-
Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258. ; 299:4
-
Tidskriftsartikel (refereegranskat)abstract
- Simple organisms are often considered to have simple gly-comes, but plentiful paucimannosidic and oligomannosidic glycans overshadow the less abundant N-glycans with highly variable core and antennal modifications; Caenorhabditis ele-gans is no exception. By use of optimized fractionation and assessing wildtype in comparison to mutant strains lacking either the HEX-4 or HEX-5 beta-N-acetylgalactosaminidases, we conclude that the model nematode has a total N-glycomic po-tential of 300 verified isomers. Three pools of glycans were analyzed for each strain: either PNGase F released and eluted from a reversed-phase C18 resin with either water or 15% methanol or PNGase Ar released. While the water-eluted frac-tions were dominated by typical paucimannosidic and oligo-mannosidic glycans and the PNGase Ar-released pools by glycans with various core modifications, the methanol-eluted fractions contained a huge range of phosphorylcholine-modified structures with up to three antennae, sometimes with four N-acetylhexosamine residues in series. There were no major differences between the C. elegans wildtype and hex-5 mutant strains, but the hex-4 mutant strains displayed altered sets of methanol-eluted and PNGase Ar-released pools. In keeping with the specificity of HEX-4, there were more glycans capped with N-acetylgalactosamine in the hex-4 mutants, as compared with isomeric chito-oligomer motifs in the wildtype. Considering that fluorescence microscopy showed that a HEX-4::enhanced GFP fusion protein colocalizes with a Golgi tracker, we conclude that HEX-4 plays a significant role in late-stage Golgi processing of N-glycans in C. elegans. Furthermore, finding more "parasite-like" structures in the model worm may facilitate discovery of glycan-processing enzymes occurring in other nematodes.
|
|
| 2. |
- Van Loenhoud, A. C., et al.
(författare)
-
High occurrence of transportation and logistics occupations among vascular dementia patients : An observational study
- 2019
-
Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Growing evidence suggests a role of occupation in the emergence and manifestation of dementia. Occupations are often defined by complexity level, although working environments and activities differ in several other important ways. We aimed to capture the multi-faceted nature of occupation through its measurement as a qualitative (instead of a quantitative) variable and explored its relationship with different types of dementia. Methods: We collected occupational information of 2121 dementia patients with various suspected etiologies from the Amsterdam Dementia Cohort (age 67 ± 8, 57% male; MMSE 21 ± 5). Our final sample included individuals with Alzheimer's disease (AD) dementia (n = 1467), frontotemporal dementia (n = 281), vascular dementia (n = 98), Lewy body disease (n = 174), and progressive supranuclear palsy/corticobasal degeneration (n = 101). Within the AD group, we used neuropsychological data to further characterize patients by clinical phenotypes. All participants were categorized into 1 of 11 occupational classes, across which we evaluated the distribution of dementia (sub)types with χ 2 analyses. We gained further insight into occupation-dementia relationships through post hoc logistic regressions that included various demographic and health characteristics as explanatory variables. Results: There were significant differences in the distribution of dementia types across occupation groups (χ 2 = 85.87, p <.001). Vascular dementia was relatively common in the Transportation/Logistics sector, and higher vascular risk factors partly explained this relationship. AD occurred less in Transportation/Logistics and more in Health Care/Welfare occupations, which related to a higher/lower percentage of males. We found no relationships between occupational classes and clinical phenotypes of AD (χ 2 = 53.65, n.s.). Conclusions: Relationships between occupation and dementia seem to exist beyond the complexity level, which offers new opportunities for disease prevention and improvement of occupational health policy.
|
|
| 3. |
- Yan, S., et al.
(författare)
-
Core Richness of N-Glycans of Caenorhabditis elegans: A Case Study on Chemical and Enzymatic Release
- 2018
-
Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 90:1, s. 928-935
-
Tidskriftsartikel (refereegranskat)abstract
- Despite years of research, the glycome of the model nematode Caenorhabditis elegans is still not fully understood. Certainly, data over the years have indicated that this organism synthesizes unusual N-glycans with a range of galactose and fucose modifications on the Man(2-3)GlcNAc(2), core region. Previously, up to four fucose residues were detected on its N-glycans, despite these lacking the fucosylated antennae typical of many other eukaryotes; some of these fucose residues are capped with hexose residues as shown by the studies of us and others. There have, though, been contrasting reports regarding the maximal number of fucose substitutions in C. elegans, which in part may be due to different methodological approaches, including use of either peptide:N-glycosidases F and A (PNGase F and A) or anhydrous hydrazine to cleave the N-glycans from glycopeptides. Here we compare the use of hydrazine with that of a new enzyme (rice PNGase Ar) and show that both enable release of glycans with more sugar residues on the proximal GlcNAc than previously resolved. By use of exoglycosidase sequencing, in conjunction with high-performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF MS/MS), we now reveal that actually up to five fucose residues modify the core region of C. elegans N-glycans and that the alpha 1,3-fucose on the reducing terminus can be substituted by an a-linked galactose. Thus, traditional PNGase F and A release may be insufficient for release of the more highly core-modified N-glycans, especially those occurring in C. elegans, but novel enzymes can compete against chemical methods in terms of safety, ease of cleanup, and quality of resulting glycomic data.
|
|
