| 1. |
|
|
| 2. |
|
|
| 3. |
- Beaney, KE, et al.
(författare)
-
Functional Analysis of the Coronary Heart Disease Risk Locus on Chromosome 21q22
- 2017
-
Ingår i: Disease markers. - : Hindawi Limited. - 1875-8630 .- 0278-0240. ; 2017, s. 1096916-
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The coronary heart disease (CHD) risk locus on 21q22 (lead SNP rs9982601) lies within a “gene desert.” The aim of this study was to assess if this locus is associated with CHD risk factors and to identify the functional variant(s) and gene(s) involved.Methods. A phenome scan was performed with UCLEB Consortium data. Allele-specific protein binding was studied using electrophoretic mobility shift assays. Dual-reporter luciferase assays were used to assess the impact of genetic variation on expression. Expression quantitative trait analysis was performed with Advanced Study of Aortic Pathology (ASAP) and Genotype-Tissue Expression (GTEx) consortium data.Results. A suggestive association between QT interval and the locus was observed (rs9982601 p=0.04). One variant at the locus, rs28451064, showed allele-specific protein binding and its minor allele showed 12% higher luciferase expression (p= 4.82 × 10−3) compared to the common allele. The minor allele of rs9982601 was associated with higher expression of the closest upstream genes (SLC5A31.30-fold increasep= 3.98 × 10−5;MRPS61.15-fold increasep= 9.60 × 10−4) in aortic intima media in ASAP. Both rs9982601 and rs28451064 showed a suggestive association withMRPS6expression in relevant tissues in the GTEx data.Conclusions. A candidate functional variant, rs28451064, was identified. Future work should focus on identifying the pathway(s) involved.
|
|
| 4. |
|
|
| 5. |
- Schenk, Linda, 1980-, et al.
(författare)
-
Industry Derived Occupational Exposure Limits : A Survey of Professionals on the Dutch System of Exposure Guidelines
- 2019
-
Ingår i: Annals of Work Exposures and Health. - : Oxford University Press. - 2398-7308 .- 2398-7316. ; 63:9, s. 1004-1012
-
Tidskriftsartikel (refereegranskat)abstract
- The Netherlands' system for occupational exposure limits (OELs) encompasses two kinds of OELs: public and private. Public OELs are set by the government. Private OELs are derived by industry and cover all substances without a public OEL. In parallel, the regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) has introduced an exposure guidance value similar to the OEL, namely the Derived No-Effect Level (DNEL) for workers' inhalation exposure. This study aimed to investigate issues encountered by occupational health professionals regarding private OELs, and how they perceive the DNELs for workers in relation to private OELs. Towards this aim, we sent out a web-based questionnaire to the members of the Dutch professional organization for occupational hygienists (Nederlandse Vereniging voor Arbeidshygiene [NVVA], n = 513) and to members of the Dutch professional organization for safety engineers (NVVK, n = 2916). Response rates were 27% (n = 139) and 7% (n = 198), respectively. More occupational hygienists (59%) than safety engineers (17%) reported to derive private OELs themselves. Our respondents reported several challenges with the derivation of private OELs. Fifty-one percent of the occupational hygienists and 20% of the safety engineers stated to see a role of REACH Registrants' worker DNELs as private OELs. However, more than half of our respondents were undecided or unfamiliar with worker DNELs. In addition, stated opinions on where worker DNELs fit in the hierarchy of private OELs varied considerably. To conclude, both these professional groups derive private OELs and stated that they need more guidance for this. Furthermore, there is a lack of clarity whether worker DNELs may qualify as private OELs, and where they would fit in the hierarchy of private OELs.
|
|
| 6. |
- van den Brand, Dirk, et al.
(författare)
-
Peptide-mediated delivery of therapeutic mRNA in ovarian cancer
- 2019
-
Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 141, s. 180-190
-
Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is the most lethal gynecological malignancy in the developed world. In spite of intensive research, the mortality has hardly decreased over the past twenty years. This necessitates the exploration of novel therapeutic modalities. Transient protein expression through delivery of mRNA is emerging as a highly promising option. In contrast to gene therapy there is no risk of integration into the genome. Here, we explore the expression of mRNA in models of ovarian cancer of increasing complexity. The cell-penetrating peptide (CPP) PepFect 14 (PF14) was used to formulate CPP-mRNA nanoparticles. Efficient expression of a reporter protein was achieved in two-dimensional tissue cultures and in three-dimensional cancer cell spheroids. PF14 nano particles greatly outperformed a lipid-based transfection agent in vivo, leading to expression in various cell types of tumor associated tissue. Protein expression was restricted to the peritoneal cavity. Messenger RNA expression across different cell types was confirmed in primary ovarian cancer explants. As ovarian cancer is confined to the peritoneal cavity in most cases, the results create the basis for applications in which the tumor microenviron-ment is transiently modified through protein expression.
|
|
