| 1. |
- Gross, Sean M., et al.
(författare)
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A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
- 2022
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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| 2. |
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| 3. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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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.
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| 4. |
- Bolatto, Alberto D., et al.
(författare)
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ALMA Imaging of a Galactic Molecular Outflow in NGC 4945
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 923:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the ALMA detection of molecular outflowing gas in the central regions of NGC 4945, one of the nearest starbursts and also one of the nearest hosts of an active galactic nucleus (AGN). We detect four outflow plumes in CO J= 3 - 2 at similar to 0.3 resolution that appear to correspond to molecular gas located near the edges of the known ionized outflow cone and its (unobserved) counterpart behind the disk. The fastest and brightest of these plumes has emission reaching observed line-of-sight projected velocities of over 450 km s(-1) beyond systemic, equivalent to an estimated physical outflow velocity v greater than or similar to 600 km s(-1) for the fastest emission. Most of these plumes have corresponding emission in HCN or HCO + J= 4 - 3. We discuss a kinematic model for the outflow emission where the molecular gas has the geometry of the ionized gas cone and shares the rotation velocity of the galaxy when ejected. We use this model to explain the velocities we observe, constrain the physical speed of the ejected material, and account for the fraction of outflowing gas that is not detected due to confusion with the galaxy disk. We estimate a total molecular mass outflow rate (M) over dot(mol) similar to 20 M-circle dot yr(-1) flowing through a surface within 100 pc of the disk midplane, likely driven by a combination of the central starburst and AGN.
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| 5. |
- Emig, Kimberly L., et al.
(författare)
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Super Star Clusters in the Central Starburst of NGC 4945
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 903:1
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Tidskriftsartikel (refereegranskat)abstract
- The nearby (3.8Mpc) galaxy NGC 4945 hosts a nuclear starburst and Seyfert type 2 active galactic nucleus (AGN). We use the Atacama Large Millimeter/submillimeter Array (ALMA) to image the 93 GHz (3.2 mm) free-free continuum and hydrogen recombination line emission (H40 alpha and H42 alpha) at 2.2 pc (0 12) resolution. Our observations reveal 27 bright, compact sources with FWHM sizes of 1.4-4.0 pc, which we identify as candidate super star clusters. Recombination line emission, tracing the ionizing photon rate of the candidate clusters, is detected in 15 sources, six of which have a significant synchrotron component to the 93 GHz continuum. Adopting an age of similar to 5Myr, the stellar masses implied by the ionizing photon luminosities are log(10) (M*/M-circle dot) approximate to 4.7-6.1. We fit a slope to the cluster mass distribution and find beta = -1.8 +/-.0.4. The gas masses associated with these clusters, derived from the dust continuum at 350 GHz, are typically an order of magnitude lower than the stellar mass. These candidate clusters appear to have already converted a large fraction of their dense natal material into stars and, given their small freefall times of similar to 0.05 Myr, are surviving an early volatile phase. We identify a pointlike source in 93 GHz continuum emission that is presumed to be the AGN. We do not detect recombination line emission from the AGN and place an upper limit on the ionizing photons that leak into the starburst region of Q(0).<.10(52) s(-1).
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| 6. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 7. |
- Harker-Schuch, Inez E. P., et al.
(författare)
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CO2peration-Structuring a 3D interactive digital game to improve climate literacy in the 12-13-year-old age group
- 2020
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Ingår i: Computers and education. - : Elsevier BV. - 0360-1315 .- 1873-782X. ; 144
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Tidskriftsartikel (refereegranskat)abstract
- Preparing students for their future and qualifying them to enter public life is the essential role of the public-school system. As such, an understanding of climate science ought to be an essential-and significant component of that preparation. This research proposes a novel pathway to teach climate science via a 3D interactive digital game and examines the potential of 12-13-year olds as a prepatent group for climate science interventions. After playing a proof-of-concept climate science game that covers the physical causes and mechanisms of climate change, 401 students in Austria and Australia were tested with a climate literacy questionnaire. Our results indicate that climate literacy can be improved in this age group via the digital game. In addition, we found further evidence of established climate science 'knowledge domains' in this age group that form a natural 'increased levels of complexity' scaffold that can be used to design curricula such as that in the digital game. These four 'knowledge domains' are (in brief): Earth in the solar system; gravity and its effect on the atmosphere; albedo and solar radiation, and; greenhouse gases and their warming potential.
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| 8. |
- Harker-Schuch, Inez, et al.
(författare)
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Opinions of 12 to 13-year-olds in Austria and Australia on the concern, cause and imminence of climate change
- 2021
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 50, s. 644-660
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Forskningsöversikt (refereegranskat)abstract
- Early adolescence (12-13 years old) is a critical but under-researched demographic for the formation of attitudes related to climate change. We address this important area by exploring adolescent views about climate change. This paper presents opinions collected from surveys of 463 1st-year secondary school students (12-13 years old) in public secondary schools in inner-urban centres in Austria and Australia on whether climate change is (1) something about which to worry, (2) caused by humans and (3) happening now. Eligible respondents in both countries showed similar levels of agreement that climate change was probably or definitely something we should (1) worry about (84.6% Austria, 89.1% Australia), which is significantly higher than either country's adult population. Eligible respondents agreed that climate change probably or definitely is (2) caused by humans (75.6% Austria, 83.6% Australia) and that climate change is probably or definitely something that is (3) happening now (73.1% Austria, 87.5% Australia). Their response differed from the respective adult populations, but in opposite directions. Our results suggest that socio-cultural worldview may not have as much influence on this age group as it does on the respective adult populations and suggests that this age group would be receptive and ready for climate science education and engagement initiatives.
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| 9. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 10. |
- Levy, Rebecca C., et al.
(författare)
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Outflows from Super Star Clusters in the Central Starburst of NGC 253
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 912:1
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Tidskriftsartikel (refereegranskat)abstract
- Young massive clusters play an important role in the evolution of their host galaxies, and feedback from the high-mass stars in these clusters can have profound effects on the surrounding interstellar medium. The nuclear starburst in the nearby galaxy NGC 253 at a distance of 3.5 Mpc is a key laboratory in which to study star formation in an extreme environment. Previous high-resolution (1.9 pc) dust continuum observations from the Atacama Large Millimeter/submillimeter Array (ALMA) discovered 14 compact, massive super star clusters (SSCs) still in formation. We present here ALMA data at 350 GHz with 28 mas (0.5 pc) resolution. We detect blueshifted absorption and redshifted emission (P-Cygni profiles) toward three of these SSCs in multiple lines, including CS 7-6 and (HCN)-C-13 4-3, which represent direct evidence for previously unobserved outflows. The mass contained in these outflows is a significant fraction of the cluster gas masses, which suggests we are witnessing a short but important phase. Further evidence of this is the finding of a molecular shell around the only SSC visible at near-IR wavelengths. We model the P-Cygni line profiles to constrain the outflow geometry, finding that the outflows must be nearly spherical. Through a comparison of the outflow properties with predictions from simulations, we find that none of the available mechanisms completely explains the observations, although dust-reprocessed radiation pressure and O star stellar winds are the most likely candidates. The observed outflows will have a very substantial effect on the clusters' evolution and star formation efficiency.
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| 11. |
- Levy, Rebecca C., et al.
(författare)
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The Morpho-kinematic Architecture of Super Star Clusters in the Center of NGC 253
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 935:1
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Tidskriftsartikel (refereegranskat)abstract
- The center of the nearby galaxy NGC 253 hosts a population of more than a dozen super star clusters (SSCs) that are still in the process of forming. The majority of the star formation of the burst is concentrated in these SSCs, and the starburst is powering a multiphase outflow from the galaxy. In this work, we measure the 350 GHz dust continuum emission toward the center of NGC 253 at 47 mas (0.8 pc) resolution using data from the Atacama Large Millimeter/submillimeter Array. We report the detection of 350 GHz (dust) continuum emission in the outflow for the first time, associated with the prominent South-West streamer. In this feature, the dust emission has a width of approximate to 8 pc, is located at the outer edge of the CO emission, and corresponds to a molecular gas mass of similar to(8-17)x10(6) M (circle dot). In the starburst nucleus, we measure the resolved radial profiles, sizes, and molecular gas masses of the SSCs. Compared to previous work at the somewhat lower spatial resolution, the SSCs here break apart into smaller substructures with radii 0.4-0.7 pc. In projection, the SSCs, dust, and dense molecular gas appear to be arranged as a thin, almost linear, structure roughly 155 pc in length. The morphology and kinematics of this structure can be well explained as gas following x (2) orbits at the center of a barred potential. We constrain the morpho-kinematic arrangement of the SSCs themselves, finding that an elliptical, angular-momentum-conserving ring is a good description of both the morphology and kinematics of the SSCs.
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| 12. |
- Maurer, Matthew, et al.
(författare)
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3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma
- 2009
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Ingår i: Cancer Research. - 1538-7445. ; 69:15, s. 306-6299
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Tidskriftsartikel (refereegranskat)abstract
- Lesions of ERBB2, PTEN, and PIK3CA activate the phosphatidylinositol 3-kinase (PI3K) pathway during cancer development by increasing levels of phosphatidylinositol-3,4,5-triphosphate (PIP(3)). 3-Phosphoinositide-dependent kinase 1 (PDK1) is the first node of the PI3K signal output and is required for activation of AKT. PIP(3) recruits PDK1 and AKT to the cell membrane through interactions with their pleckstrin homology domains, allowing PDK1 to activate AKT by phosphorylating it at residue threonine-308. We show that total PDK1 protein and mRNA were overexpressed in a majority of human breast cancers and that 21% of tumors had five or more copies of the gene encoding PDK1, PDPK1. We found that increased PDPK1 copy number was associated with upstream pathway lesions (ERBB2 amplification, PTEN loss, or PIK3CA mutation), as well as patient survival. Examination of an independent set of breast cancers and tumor cell lines derived from multiple forms of human cancers also found increased PDK1 protein levels associated with such upstream pathway lesions. In human mammary cells, PDK1 enhanced the ability of upstream lesions to signal to AKT, stimulate cell growth and migration, and rendered cells more resistant to PDK1 and PI3K inhibition. After orthotopic transplantation, PDK1 overexpression was not oncogenic but dramatically enhanced the ability of ERBB2 to form tumors. Our studies argue that PDK1 overexpression and increased PDPK1 copy number are common occurrences in cancer that potentiate the oncogenic effect of upstream lesions on the PI3K pathway. Therefore, we conclude that alteration of PDK1 is a critical component of oncogenic PI3K signaling in breast cancer.
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| 13. |
- Ossler, Frederik, et al.
(författare)
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Dynamics of hydrogen loss and structural changes in pyrolyzing biomass utilizing neutron imaging
- 2021
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Ingår i: Carbon. - : Elsevier BV. - 0008-6223. ; 176, s. 511-529
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Tidskriftsartikel (refereegranskat)abstract
- We present results from neutron-imaging studies of slow, vacuum pyrolysis of beech, poplar and conifer wood, and pelletized biomass from room temperature up to 1000 °C. A detailed and quantitative method to extract 2D (in situ neutron radiography, NR) and 3D (ex situ neutron computed tomography, NCT) information on structural transformation and elemental hydrogen content has been developed. NCT and X-ray tomography (XCT) experiments on a carbonized beech twig permitted comparison of the spatial distribution of hydrogen, better sensed by NCT, and carbon, oxygen, and heavier elements, better sensed by XCT. We have developed a methodology to directly compare structure and hydrogen-loss dynamics measured using neutron imaging with thermogravimetric analysis and differential thermogravimetry and thus can better understand the correlations between hydrogen and carbon release dynamics. While the methodology has been developed for the carbonization of biomass, we expect that it could be applied to in situ dynamic monitoring of other hydrogenous reacting systems with the appropriate spatial and temporal scales.
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| 14. |
- Ossler, Frederik, et al.
(författare)
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In situ monitoring of hydrogen loss during pyrolysis of wood by neutron imaging
- 2019
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Ingår i: Proceedings of the Combustion Institute. - : Elsevier BV. - 1540-7489. ; 37:2, s. 1273-1280
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Tidskriftsartikel (refereegranskat)abstract
- Hydrogen is an element of fundamental importance for energy but hard to quantify in bulk materials. Neutron radiography was used to map . in situ loss of elemental hydrogen from beech tree wood samples during pyrolysis. The samples consisted of three wood cylinders (finished dowel or cut branch) of approximately 1 cm in length. The samples were pyrolyzed under vacuum in a furnace vessel that was placed inside a cold neutron imaging beamline using a temperature ramp of 5 °C/min from ambient up to 400 °C. Neutron radiographs with exposures of 30 s were sequentially recorded with a charge-coupled device over the course of the experiment. Relative absorbance/scattering of the neutron beam by each sample was based on intensity (or brightness) values as a function of pixel position. The much larger neutron cross section for hydrogen compared to carbon and oxygen enables almost direct conversion of neutron attenuation into sample hydrogen content for each time step during the pyrolysis experiment. Target and vessel temperatures were recorded concurrently with collection of the radiographs so that changes could be directly correlated to different states of pyrolysis. The most visible change appeared at the initial phase of the 400 °C plateau as evidenced by strong hydrogen loss and primarily diametric shrinking of the samples. The loss of elemental hydrogen between initial and final states of pyrolysis was estimated to be about 70%.
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| 15. |
- Ried, Janina S., et al.
(författare)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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| 16. |
- Rust, Niki A., et al.
(författare)
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Have farmers had enough of experts?
- 2022
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Ingår i: Environmental Management. - : Springer New York. - 0364-152X .- 1432-1009. ; 69:1, s. 31-44
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Tidskriftsartikel (refereegranskat)abstract
- The exponential rise of information available means we can now, in theory, access knowledge on almost any question we ask. However, as the amount of unverified information increases, so too does the challenge in deciding which information to trust. Farmers, when learning about agricultural innovations, have historically relied on in-person advice from traditional ‘experts’, such as agricultural advisers, to inform farm management. As more farmers go online for information, it is not clear whether they are now using digital information to corroborate in-person advice from traditional ‘experts’, or if they are foregoing ‘expert’ advice in preference for peer-generated information. To fill this knowledge gap, we sought to understand how farmers in two contrasting European countries (Hungary and the UK) learnt about sustainable soil innovations and who influenced them to innovate. Through interviews with 82 respondents, we found farmers in both countries regularly used online sources to access soil information; some were prompted to change their soil management by farmer social media ‘influencers’. However, online information and interactions were not usually the main factor influencing farmers to change their practices. Farmers placed most trust in other farmers to learn about new soil practices and were less trusting of traditional ‘experts’, particularly agricultural researchers from academic and government institutions, who they believed were not empathetic towards farmers’ needs. We suggest that some farmers may indeed have had enough of traditional ‘experts’, instead relying more on their own peer networks to learn and innovate. We discuss ways to improve trustworthy knowledge exchange between agricultural stakeholders to increase uptake of sustainable soil management practices, while acknowledging the value of peer influence and online interactions for innovation and trust building.
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| 17. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 18. |
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