| 61. |
- Kuhn, McKenzie A., et al.
(författare)
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Opposing Effects of Climate and Permafrost Thaw on CH4 and CO2 Emissions From Northern Lakes
- 2021
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Ingår i: AGU Advances. - : American Geophysical Union (AGU). - 2576-604X. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Small, organic-rich lakes are important sources of methane (CH4) and carbon dioxide (CO2) to the atmosphere, yet the sensitivity of emissions to climate warming is poorly constrained and potentially influenced by permafrost thaw. Here, we monitored emissions from 20 peatland lakes across a 1,600 km permafrost transect in boreal western Canada. Contrary to expectations, we observed a shift from source to sink of CO2 for lakes warmer regions, driven by greater primary productivity associated with greater hydrological connectivity to lakes and nutrient availability in the absence of permafrost. Conversely, an 8-fold increase in CH4 emissions in warmer regions was associated with water temperature and shifts in microbial communities and dominant anaerobic processes. Our results suggest that the net radiative forcing from altered greenhouse gas emissions of northern peatland lakes this century will be dominated by increasing CH4 emissions and only partially offset by reduced CO2 emissions.
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| 62. |
- Lucas, Gavin, et al.
(författare)
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Hypothesis-Based Analysis of Gene-Gene Interactions and Risk of Myocardial Infarction
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- The genetic loci that have been found by genome-wide association studies to modulate risk of coronary heart disease explain only a fraction of its total variance, and gene-gene interactions have been proposed as a potential source of the remaining heritability. Given the potentially large testing burden, we sought to enrich our search space with real interactions by analyzing variants that may be more likely to interact on the basis of two distinct hypotheses: a biological hypothesis, under which MI risk is modulated by interactions between variants that are known to be relevant for its risk factors; and a statistical hypothesis, under which interacting variants individually show weak marginal association with MI. In a discovery sample of 2,967 cases of early-onset myocardial infarction (MI) and 3,075 controls from the MIGen study, we performed pair-wise SNP interaction testing using a logistic regression framework. Despite having reasonable power to detect interaction effects of plausible magnitudes, we observed no statistically significant evidence of interaction under these hypotheses, and no clear consistency between the top results in our discovery sample and those in a large validation sample of 1,766 cases of coronary heart disease and 2,938 controls from the Wellcome Trust Case-Control Consortium. Our results do not support the existence of strong interaction effects as a common risk factor for MI. Within the scope of the hypotheses we have explored, this study places a modest upper limit on the magnitude that epistatic risk effects are likely to have at the population level (odds ratio for MI risk 1.3-2.0, depending on allele frequency and interaction model).
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| 63. |
- Moore, Josh, et al.
(författare)
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OME-Zarr : A cloud-optimized bioimaging file format with international community support
- 2023
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Ingår i: Histochemistry and Cell Biology. - : Springer Nature. - 1432-119X .- 0948-6143. ; 160:3, s. 223-251
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Tidskriftsartikel (refereegranskat)abstract
- A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself-OME-Zarr-along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process. The current momentum offers an opportunity to unify a key component of the bioimaging domain-the file format that underlies so many personal, institutional, and global data management and analysis tasks.
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| 64. |
- Raval, Aparna, et al.
(författare)
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Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia
- 2007
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 129:5, s. 879-890
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Tidskriftsartikel (refereegranskat)abstract
- The heritability of B cell chronic lymphocytic leukemia (CLL) is relatively high; however, no predisposing mutation has been convincingly identified. We show that loss or reduced expression of death-associated protein kinase 1 (DAPK1) underlies cases of heritable predisposition to CLL and the majority of sporadic CLL. Epigenetic silencing of DAPK1 by promoter methylation occurs in almost all sporadic CLL cases. Furthermore, we defined a disease haplotype, which segregates with the CLL phenotype in a large family. DAPK1 expression of the CLL allele is downregulated by 75% in germline cells due to increased HOXB7 binding. In the blood cells from affected family members, promoter methylation results in additional loss of DAPK1 expression. Thus, reduced expression of DAPK1 can result from germline predisposition, as well as epigenetic or somatic events causing or contributing to the CLL phenotype.
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| 65. |
- Andrady, Anthony, et al.
(författare)
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Environmental effects of ozone depletion and its interactions with climate change: Progress report, 2016
- 2017
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Ingår i: Photochemical and Photobiological Sciences. - : Springer Science and Business Media LLC. - 1474-9092 .- 1474-905X. ; 16:2, s. 107-145
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Tidskriftsartikel (refereegranskat)abstract
- The Parties to the Montreal Protocol are informed by three Panels of experts. One of these is the Environmental Effects Assessment Panel (EEAP), which deals with two focal issues. The first focus is the effects of UV radiation on human health, animals, plants, biogeochemistry, air quality, and materials. The second focus is on interactions between UV radiation and global climate change and how these may affect humans and the environment. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously believed. As a result of this, human health and environmental issues will be longer-lasting and more regionally variable. Like the other Panels, the EEAPproduces a detailed report every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1–184). In the years in between, the EEAP produces less detailed and shorter Progress Reports of the relevant scientific findings. The most recent of these was for 2015 (Photochem. Photobiol. Sci., 2016, 15, 141–147). The present Progress Report for 2016 assesses some of the highlights and new insights with regard to the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. The more detailed Quadrennial Assessment will bemade available in 2018.
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| 66. |
- Bjelic, Sinisa, et al.
(författare)
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Computational design of enone-binding proteins with catalytic activity for the Morita-Baylis-Hillman reaction
- 2013
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 8:4, s. 749-757
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Tidskriftsartikel (refereegranskat)abstract
- The Morita-Baylis-Hillman reaction forms a carbon-carbon bond between the α-carbon of a conjugated carbonyl compound and a carbon electrophile. The reaction mechanism involves Michael addition of a nucleophile catalyst at the carbonyl β-carbon, followed by bond formation with the electrophile and catalyst disassociation to release the product. We used Rosetta to design 48 proteins containing active sites predicted to carry out this mechanism, of which two show catalytic activity by mass spectrometry (MS). Substrate labeling measured by MS and site-directed mutagenesis experiments show that the designed active-site residues are responsible for activity, although rate acceleration over background is modest. To characterize the designed proteins, we developed a fluorescence-based screen for intermediate formation in cell lysates, carried out microsecond molecular dynamics simulations, and solved X-ray crystal structures. These data indicate a partially formed active site and suggest several clear avenues for designing more active catalysts.
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| 67. |
- Brütt, Katharina, et al.
(författare)
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Competition and moral behavior: A meta-analysis of forty-five crowd-sourced experimental designs
- 2023
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Ingår i: Proceedings of the National Academy of Sciences - PNAS. - : National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 120:23
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Tidskriftsartikel (refereegranskat)abstract
- Does competition affect moral behavior? This fundamental question has been debated among leading scholars for centuries, and more recently, it has been tested in experimental studies yielding a body of rather inconclusive empirical evidence. A potential source of ambivalent empirical results on the same hypothesis is design heterogeneity-variation in true effect sizes across various reasonable experimental research protocols. To provide further evidence on whether competition affects moral behavior and to examine whether the generalizability of a single experimental study is jeopardized by design heterogeneity, we invited independent research teams to contribute experimental designs to a crowd-sourced project. In a large-scale online data collection, 18,123 experimental participants were randomly allocated to 45 randomly selected experimental designs out of 95 submitted designs. We find a small adverse effect of competition on moral behavior in a meta-analysis of the pooled data. The crowd-sourced design of our study allows for a clean identification and estimation of the variation in effect sizes above and beyond what could be expected due to sampling variance. We find substantial design heterogeneity-estimated to be about 1.6 times as large as the average standard error of effect size estimates of the 45 research designs-indicating that the informativeness and generalizability of results based on a single experimental design are limited. Drawing strong conclusions about the underlying hypotheses in the presence of substantive design heterogeneity requires moving toward much larger data collections on various experimental designs testing the same hypothesis.
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| 68. |
- Chen, Baoqing, et al.
(författare)
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The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 159:6, s. 2146-2162
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Tidskriftsartikel (refereegranskat)abstract
- Background & AimsChromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer–associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.MethodsWe performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2′-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients.ResultsHigh expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients.ConclusionsWe found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.
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| 69. |
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| 70. |
- Dixon, P. Grady, et al.
(författare)
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Perspectives on the Synoptic Climate Classification and its Role in Interdisciplinary Research
- 2016
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Ingår i: Geography Compass. - : Wiley. - 1749-8198. ; 10:4, s. 147-164
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Tidskriftsartikel (refereegranskat)abstract
- Synoptic climatology has a long history of research where weather data are aggregated and composited to gain a better understanding of atmospheric effects on non-atmospheric variables. This has resulted in an applied scientific discipline that yields methods and tools designed for applications across disciplinary boundaries. The spatial synoptic classification (SSC) is an example of such a tool that helps researchers bridge methodological gaps between disciplines, especially those studying weather effects on human health. The SSC has been applied in several multi-discipline projects, and it appears that there is ample opportunity for growth into new topical areas. Likewise, there is opportunity for the SSC network to be expanded across the globe, especially into mid-latitude locations in the Southern Hemisphere. There is some question of the utility of the SSC in tropical locations, but such decisions must be based on the actual weather data from individual locations. Despite all of the strengths and potential uses of the SSC, there are some research problems, some locations, and some datasets for which it is not suitable. Nevertheless, the success of the SSC as a cross-disciplinary method is noteworthy because it has become a catalyst for collaboration.
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