| 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. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 3. |
- Abbafati, Cristiana, et al.
(författare)
-
- 2020
-
Tidskriftsartikel (refereegranskat)
|
|
| 4. |
- Docherty, Anna R, et al.
(författare)
-
GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
-
Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
-
Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
|
|
| 5. |
- Ebersole, Charles R., et al.
(författare)
-
Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
-
Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
-
Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
|
|
| 6. |
- Jayasekara, Harindra, et al.
(författare)
-
Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer : A pooled analysis of data from two prospective cohort studies
- 2021
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 148:11, s. 2759-2773
-
Tidskriftsartikel (refereegranskat)abstract
- Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity =.02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.
|
|
| 7. |
- Lillis, Robert J., et al.
(författare)
-
MOSAIC: A satellite constellation to enable groundbreaking mars climate system science and prepare for human exploration
- 2021
-
Ingår i: Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 2:5
-
Tidskriftsartikel (refereegranskat)abstract
- The Martian climate system has been revealed to rival the complexity of Earth's. Over the last 20 yr, a fragmented and incomplete picture has emerged of its structure and variability; we remain largely ignorant of many of the physical processes driving matter and energy flow between and within Mars' diverse climate domains. Mars Orbiters for Surface, Atmosphere, and Ionosphere Connections (MOSAIC) is a constellation of ten platforms focused on understanding these climate connections, with orbits and instruments tailored to observe the Martian climate system from three complementary perspectives. First, low-circular near-polar Sun-synchronous orbits (a large mothership and three smallsats spaced in local time) enable vertical profiling of wind, aerosols, water, and temperature, as well as mapping of surface and subsurface ice. Second, elliptical orbits sampling all of Mars' plasma regions enable multipoint measurements necessary to understand mass/energy transport and ion-driven escape, also enabling, with the polar orbiters, dense radio occultation coverage. Last, longitudinally spaced areostationary orbits enable synoptic views of the lower atmosphere necessary to understand global and mesoscale dynamics, global views of the hydrogen and oxygen exospheres, and upstream measurements of space weather conditions. MOSAIC will characterize climate system variability diurnally and seasonally, on meso-, regional, and global scales, targeting the shallow subsurface all the way out to the solar wind, making many first-of-their-kind measurements. Importantly, these measurements will also prepare for human exploration and habitation of Mars by providing water resource prospecting, operational forecasting of dust and radiation hazards, and ionospheric communication/positioning disruptions.
|
|
| 8. |
- Nava, Veronica, et al.
(författare)
-
Plastic debris in lakes and reservoirs
- 2023
-
Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 619:7969, s. 317-322
-
Tidskriftsartikel (refereegranskat)abstract
- Plastic debris is thought to be widespread in freshwater ecosystems globally(1). However, a lack of comprehensive and comparable data makes rigorous assessment of its distribution challenging(2,3). Here we present a standardized cross-national survey that assesses the abundance and type of plastic debris (>250 mu m) in freshwater ecosystems. We sample surface waters of 38 lakes and reservoirs, distributed across gradients of geographical position and limnological attributes, with the aim to identify factors associated with an increased observation of plastics. We find plastic debris in all studied lakes and reservoirs, suggesting that these ecosystems play a key role in the plastic-pollution cycle. Our results indicate that two types of lakes are particularly vulnerable to plastic contamination: lakes and reservoirs in densely populated and urbanized areas and large lakes and reservoirs with elevated deposition areas, long water-retention times and high levels of anthropogenic influence. Plastic concentrations vary widely among lakes; in the most polluted, concentrations reach or even exceed those reported in the subtropical oceanic gyres, marine areas collecting large amounts of debris(4). Our findings highlight the importance of including lakes and reservoirs when addressing plastic pollution, in the context of pollution management and for the continued provision of lake ecosystem services.
|
|
| 9. |
- Potapov, Anton M., et al.
(författare)
-
Global fine-resolution data on springtail abundance and community structure
- 2024
-
Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.
|
|
| 10. |
- Raj, Satish R, et al.
(författare)
-
Postural orthostatic tachycardia syndrome (POTS) : Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2
- 2021
-
Ingår i: Autonomic Neuroscience: Basic & Clinical. - : Elsevier BV. - 1872-7484. ; 235
-
Tidskriftsartikel (refereegranskat)abstract
- The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area.
|
|
