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- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 5. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 10. |
- Zhu, Y., et al.
(författare)
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Catalytic pyrolysis of duckweed with phosphoric acid : Pyrolysis behavior and kinetics analysis
- 2024
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Ingår i: Journal of Analytical and Applied Pyrolysis. - : Elsevier BV. - 0165-2370 .- 1873-250X. ; 177
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Tidskriftsartikel (refereegranskat)abstract
- Duckweed (DW) has a promising potential for wastewater treatment due to its outstanding performance in the fixation of nutrient elements and heavy metals. The conversion of harvested duckweed into value-added products through pyrolysis is an attractive method for duckweed utilization as fuels or chemicals. In this work, the duckweed was prepared by deashing treatment and subsequent impregnation with different phosphoric acid concentrations (ADW-P). The pyrolysis behavior and kinetics of raw and impregnated duckweeds were studied with respect to the ash contained in the duckweed and the phosphoric acid catalytic effect by thermogravimetric analysis-fourier transform infrared spectrometer (TG-FTIR) and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The results show that the pyrolysis reaction zone is extended for the impregnated duckweed by reducing the initial pyrolysis temperature and increasing the final temperature. Specifically, a shoulder peak situated at the right side of the main peak is present in the DTG curves of ADW-P, suggesting the formation of relatively stable substance after phosphoric acid impregnation. Phosphoric acid promotes the release of H2O, CH4, CO2 and NH3 as well as light volatiles with C[dbnd]C and C[dbnd]O groups during pyrolysis. Meanwhile, decarboxylation and aromatization as well as deamination of organic compounds are strengthened, resulting in an increase of aromatic hydrocarbons and furans and a decrease of N-heterocyclic compounds. The activation energy of ADW-P is lower than that of DW and ADW at conversion rate less than 75% but increases remarkably at high conversion rate. This implies that phosphoric acid facilitates the thermal decomposition of DW at low temperatures but hinders its decomposition at high temperatures probably due to the formation of stable cross-linked structures such as phosphate and polyphosphate esters.
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