| 1. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 2. |
- Su, Zhan, et al.
(författare)
-
Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
-
Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
|
|
| 3. |
|
|
| 4. |
- Anvret, Anna, et al.
(författare)
-
Possible involvement of a mitochondrial translation initiation factor 3 variant causing decreased mRNA levels in Parkinson's disease.
- 2010
-
Ingår i: Parkinson's disease. - : Hindawi Limited. - 2042-0080. ; 2010
-
Tidskriftsartikel (refereegranskat)abstract
- Genes important for mitochondrial function have been implicated in Parkinson's disease (PD). Mitochondrial translation initiation factor 3 (MTIF3) is a nuclear encoded protein required for the initiation of complex formation on mitochondrial ribosomes. Dysfunction of MTIF3 may impair mitochondrial function and dopamine neurons appear to be particularly vulnerable to oxidative stress, which may relate to their degeneration in PD. An association was recently reported between the synonymous rs7669(C>T) in MTIF3 and PD in a German case-control material. We investigated rs7669 in a Swedish Parkinson case-control material. The study revealed no significant association of the individual genotypes or alleles with PD. When comparing the combined TT/CT-genotypes versus the CC-genotype, we observed a significant association (P = .0473) with PD. We also demonstrated that the TT-genotype causes a significant decrease in MTIF3 mRNA expression compared to the CC-genotype (P = .0163). Our findings support the hypothesis that MTIF3 may be involved in the etiology of PD.
|
|
| 5. |
- Aspholm-Hurtig, Marina, et al.
(författare)
-
Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
-
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
-
Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
|
|
| 6. |
- Berndt, Sonja I., et al.
(författare)
-
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
-
Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
|
|
| 7. |
- Bessell, Michael S., et al.
(författare)
-
Nucleosynthesis in a Primordial Supernova : Carbon and Oxygen Abundances in SMSS J031300.36-670839.3
- 2015
-
Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 806:1
-
Tidskriftsartikel (refereegranskat)abstract
- SMSS J031300.36-670839.3 (hereafter SM0313-6708) is a sub-giant halo star, with no detectable Fe lines and large overabundances of C and Mg relative to Ca. We obtained Very Large Telescope-Ultraviolet and Visual Echelle Spectrograph (UVES) spectra extending to 3060 angstrom showing strong OH A-X band lines enabling an oxygen abundance to be derived. The OH A-X band lines in SM0313-6708 are much stronger than the CH C-X band lines. Spectrum synthesis fits indicate an [O/C] ratio of 0.02 +/- 0.175. Our high signal-to-noise ratio UVES data also enabled us to lower the Fe abundance limit to [Fe/H](< 3D >,NLTE) < -7.52 (3 sigma). These data support our previous suggestion that the star formed from the iron-poor ejecta of a single massive star Population III supernova.
|
|
| 8. |
- Carland, Corinne, et al.
(författare)
-
Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases
- 2023
-
Ingår i: Clinical Proteomics. - : BMC. - 1542-6416 .- 1559-0275. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance.Methods: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins.Results: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F).Conclusion: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases.
|
|
| 9. |
- Dunder, Linda, et al.
(författare)
-
Changes in plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with changes in plasma lipids : A longitudinal study over 10 years
- 2022
-
Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 211
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between per- and polyfluoroalkyl substances (PFAS), mainly PFOS and PFOA, and increased blood lipids have been reported primarily from cross-sectional studies. The aim of the present study was to investigate associations between multiple PFAS and blood lipids in a longitudinal fashion.METHODS: A total of 864 men and women aged 70 years and free from lipid medication were included from the PIVUS study, 614 and 404 of those were reinvestigated at age 75 and 80. At all three occasions, eight PFAS were measured in plasma using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were also measured in plasma at all three occasions. Mixed-effects linear regression models were used to examine the relationship between the changes in PFAS levels and changes in lipid levels.RESULTS: Changes in plasma levels of six out of the eight investigated PFAS were positively associated with changes in plasma lipids after adjustment for sex, change in body mass index (BMI), smoking, physical activity, statin use (age was the same in all subjects), and correction for multiple testing. For example, changes in perfluorodecanoic acid (PFDA) were positively associated with the changes in total cholesterol (β: 0.23, 95% confidence interval (CI): 0.14 to 0.32), triglycerides (β: 0.08, 95% CI: 0.04-0.12) and HDL-cholesterol (β: 0.08, 95% CI: 0.04-0.11).CONCLUSION: In this longitudinal study with three measurements over 10 years of both plasma PFAS and lipids, changes in six out of the eight investigated PFAS were positively associated with changes in plasma lipids, giving further support for a role of PFAS exposure in human lipid metabolism.
|
|
| 10. |
- Dunder, Linda
(författare)
-
Exposure to Bisphenol A (BPA) and Metabolic Disruption
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Metbolic disorders such as obesity, type 2 diabetes, liver lipid disorders and metabolic syndrome are increasing rapidly and have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence showing that other environmental factors, including environmental chemicals, may contribute to the rapid increase in the incidence of these metabolic diseases. Of particular growing concern is low-dose developmental exposure to endocrine disrupting chemicals (EDCs). The developing period is an extremely sensitive window of exposure to environmental stressors, including EDCs, and early life exposure has been linked to metabolic disorders later in life. Consistent with hormones, EDCs can act at very low serum concentrations and even small changes in the endocrine system may lead to extensive effects. The overall aim of this thesis has been to investigate potential metabolic disruption following exposure to Bisphenol A (BPA), which is a known EDC. The experimental animal study demonstrated that male and female rat offspring generally exhibited differential susceptibility to developmental exposure to BPA (0.5 µg/kg BW/day or 50 µg/kg BW/day). The main results showed that the lowest dose of BPA induced increased plasma triglyceride levels and increased adipocyte cell density in inguinal white adipose tissue in female offspring. Further, this low dose increased fatty acid indices and altered the fatty acid composition in male offspring and enhanced insulin secretion in pancreatic islets from male and female offspring and dams. Contrastingly, the higher BPA-dose decreased insulin secretion in pancreatic islets from male and female offspring and dams. The increased fatty acid indices, and the altered fatty acid composition together with enhanced insulin secretion may be early risk factors for insulin resistance. Furthermore, depending on the tissue, dose and sex, BPA altered the expression of genes involved in lipid and adipocyte homeostasis.The epidemiological study with a meta-analysis of data from the National Health and Nutrition Survey (NHANES) did not disclose any associations between urinary BPA and dyslipidemia. However, considering the cross-sectional nature of the present study, this should rather be investigated in carefully designed prospective cohort studies with repeated BPA measurements. Nonetheless, we hope that this paper can encourage researchers to evaluate NHANES data using meta-analyses instead of pooling of data.This thesis concludes that exposure to BPA, which is a known EDC, most likely is a contributor, along with genetic, social and behavioral factors, to the development of metabolic disorders.
|
|
