| 1. |
- Cai, G-H, et al.
(författare)
-
Quantitative PCR analysis of fungal DNA in Swedish day care centers and comparison with building characteristics and allergen levels
- 2009
-
Ingår i: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 19:5, s. 392-400
-
Tidskriftsartikel (refereegranskat)abstract
- Sweden has had allergen-avoidance day care centers (AADCs) since 1979. The aim of this study was to measure fungal DNA by quantitative polymerase chain reaction (qPCR), a new method, in AADCs and ordinary day care centers (ODCs) and examine associations between allergen levels and building characteristics. Dust samples were collected by swabbing doorframes, vacuum-cleaning, and using Petri dishes. In total, 11 AADCs and 11 ODCs were studied (70 rooms). Total fungal DNA, measured by qPCR in the swab dust, was detected in 89%, Aspergillus or Penicillium (Asp/Pen) DNA in 34%, and Stachybotrys chartarum DNA in 6% of the rooms. Total fungal DNA was significantly higher in rooms with linoleum floor (P = 0.02), textile carpets (P = 0.03), reported dampness/molds (P = 0.02) and reported odor (P < 0.001) in the buildings, and significantly lower in wooden facade buildings (P = 0.003). Reported odor was related to the amount of sieved fine dust, reported dampness/molds and type of building construction. Total fungal DNA was related to cat, dog, horse and total allergen levels (P = 0.003) in the day care centers. In conclusion, total fungal DNA is related to reported dampness/molds, reported odor, and type of wall construction. The association between fungal and allergen contamination indicated a general 'hygiene factor' related to biological contaminants. Practical Implications The associations between fungal DNA, reported dampness/molds, and odor support the view that buildings with odor problems should be investigated for possible hidden fungal growth. There is a need to measure fungal biomass in different types of building constructions by monitoring fungal DNA. Analysis of fungal DNA with quantitative PCR can be a fast and practical way to study indoor fungal contamination. Swabbing dust from the doorframe of the main entrance to the room can be a convenient method of sampling dust for fungal DNA analysis. The high prevalence of reported dampness/molds and the common occurrence of fungal DNA indicate the need to improve the indoor environment of Swedish day care centers.
|
|
| 2. |
- Klaric, Lucija, et al.
(författare)
-
Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
-
Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
|
|
| 3. |
- Mälarstig, Anders, et al.
(författare)
-
Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer. We present 812 cis-acting protein quantitative trait loci for 737 proteins which are used as instruments in Mendelian randomisation analyses of breast cancer risk. Of those, we present five proteins (CD160, DNPH1, LAYN, LRRC37A2 and TLR1) that show a potential causal role in breast cancer risk with confirmatory results in independent cohorts. Our study suggests that these proteins should be further explored as biomarkers and potential drug targets in breast cancer.
|
|
| 4. |
- Smith-Byrne, Karl, et al.
(författare)
-
Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
- 2024
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins can reveal key pathways to cancer and identify therapeutic targets for cancer prevention. We investigate 2,074 circulating proteins and risk of nine common cancers (bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma) using cis protein Mendelian randomisation and colocalization. We conduct additional analyses to identify adverse side-effects of altering risk proteins and map cancer risk proteins to drug targets. Here we find 40 proteins associated with common cancers, such as PLAUR and risk of breast cancer [odds ratio per standard deviation increment: 2.27, 1.88-2.74], and with high-mortality cancers, such as CTRB1 and pancreatic cancer [0.79, 0.73-0.85]. We also identify potential adverse effects of protein-altering interventions to reduce cancer risk, such as hypertension. Additionally, we report 18 proteins associated with cancer risk that map to existing drugs and 15 that are not currently under clinical investigation. In sum, we identify protein-cancer links that improve our understanding of cancer aetiology. We also demonstrate that the wider consequence of any protein-altering intervention on well-being and morbidity is required to interpret any utility of proteins as potential future targets for therapeutic prevention.
|
|
