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- 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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- Fang, MY, et al.
(författare)
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T Cell Repertoire Abnormality in Immunodeficiency Patients with DNA Repair and Methylation Defects
- 2022
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 1573-2592 .- 0271-9142. ; 42:2, s. 375-393
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Tidskriftsartikel (refereegranskat)abstract
- Both DNA damage response and methylation play a crucial role in antigen receptor recombination by creating a diverse repertoire in developing lymphocytes, but how their defects relate to T cell repertoire and phenotypic heterogeneity of immunodeficiency remains obscure. We studied the TCR repertoire in patients with the mutation in different genes (ATM, DNMT3B,ZBTB24,RAG1,DCLRE1C, andJAK3) and uncovered distinct characteristics of repertoire diversity. We propose that early aberrancies in thymus T cell development predispose to the heterogeneous phenotypes of the immunodeficiency spectrum. Shorter CDR3 lengths in ATM-deficient patients, resulting from a decreased number of nucleotide insertions during VDJ recombination in the pre-selected TCR repertoire, as well as the increment of CDR3 tyrosine residues, lead to the enrichment of pathology-associated TCRs, which may contribute to the phenotypes of ATM deficiency. Furthermore, patients withDNMT3BandZBTB24mutations who exhibit discrepant phenotypes present longer CDR3 lengths and reduced number of known pathology-associated TCRs.
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- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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- Wu, ZC, et al.
(författare)
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Tumor suppressor ZHX2 inhibits NAFLD-HCC progression via blocking LPL-mediated lipid uptake
- 2020
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 27:5, s. 1693-1708
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Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) leads to hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. Here, we investigated the role of the tumor suppressor Zinc fingers and homeoboxes 2 (ZHX2) in the progression of NAFLD to HCC. ZHX2 expression was significantly decreased in fatty liver tissues, especially in the liver with NAFLD–HCC. ZHX2 overexpression disturbed lipid homeostasis of cultured HCC cells, and inhibited lipid deposition in hepatocytes both in vitro and in vivo. Moreover, ZHX2 inhibited uptake of exogenous lipids through transcriptional suppression of lipid lipase (LPL), leading to retarded proliferation of HCC cells. Importantly, LPL overexpression significantly reversed ZHX2-mediated inhibition of HCC cell proliferation, xenograft tumor growth, lipid deposition, and spontaneous liver tumor formation. Consistently, IHC staining demonstrated a negative correlation of ZHX2 with LPL in an HCC cohort. Collectively, ZHX2 protects hepatocytes from abnormal lipid deposition in NAFLD through transcriptional repression of LPL, which subsequently retards cell growth and NAFLD–HCC progression. These findings illustrate a novel mechanism of NAFLD progression into HCC.
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- Cao, LY, et al.
(författare)
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Deciphering Molecular Mechanism Underlying Self-Flocculation of Zymomonas mobilis for Robust Production
- 2022
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Ingår i: Applied and environmental microbiology. - : American Society for Microbiology. - 1098-5336 .- 0099-2240. ; 88:9, s. e0239821-
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Tidskriftsartikel (refereegranskat)abstract
- Stress tolerance is a prerequisite for microbial cell factories to be robust in production, particularly for biorefinery of lignocellulosic biomass to produce biofuels, bioenergy, and bio-based chemicals for sustainable socioeconomic development, since various inhibitors are released during the pretreatment to destroy the recalcitrant lignin-carbohydrate complex for sugar production through enzymatic hydrolysis of the cellulose component, and their detoxification is too costly for producing bulk commodities. Although tolerance to individual stress has been intensively studied, the progress seems less significant since microbial cells are inevitably suffering from multiple stresses simultaneously under production conditions.
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| 28. |
- Ji, FL, et al.
(författare)
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The Genetic Architecture of the Clustering of Cardiometabolic Risk Factors: A Study of 8- to 17-Year-Old Chinese Twins
- 2020
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Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 23:5, s. 283-291
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Tidskriftsartikel (refereegranskat)abstract
- We explored the genetic architecture of metabolic risk factors of cardiovascular diseases (CVDs) and their clustering in Chinese boys and girls. Seven metabolic traits (body mass index [BMI], waist circumference [WC], systolic blood pressure [SBP], diastolic blood pressure [DBP], total cholesterol [TC], triglyceride [TG], and uric acid [UA]) were measured in a sample of 1016 twins between 8 and 17 years of age, recruited from the Qingdao Twin Registry. Cholesky, independent pathway, and common pathway models were used to identify the latent genetic structure behind the clustering of these metabolic traits. Genetic architecture of these metabolic traits was largely similar in boys and girls. The highest heritability was found for BMI (a2 = 0.63) in boys and TC (a2 = .69) in girls. Three heritable factors, adiposity (BMI and WC), blood pressure (SBP and DBP), and metabolite factors (TC, TG, and UA), which formed one higher-order latent phenotype, were identified. Latent genetic, common environmental, and unique environmental factors indirectly impacted the three factors through one single latent factor. Our results suggest that there is one latent factor influencing several metabolic traits, which are known risk factors of CVDs in young Chinese twins. Latent genetic, common environmental, and unique environmental factors indirectly imposed on them. These results inform strategies for gene pleiotropic discovery and intervening of CVD risk factors during childhood and adolescence.
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| 33. |
- Zhang, D, et al.
(författare)
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Spatial epigenome-transcriptome co-profiling of mammalian tissues
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615616:79547955, s. 113-122
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Tidskriftsartikel (refereegranskat)abstract
- Emerging spatial technologies, including spatial transcriptomics and spatial epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context1–5. However, current methods capture only one layer of omics information at a time, precluding the possibility of examining the mechanistic relationship across the central dogma of molecular biology. Here, we present two technologies for spatially resolved, genome-wide, joint profiling of the epigenome and transcriptome by cosequencing chromatin accessibility and gene expression, or histone modifications (H3K27me3, H3K27ac or H3K4me3) and gene expression on the same tissue section at near-single-cell resolution. These were applied to embryonic and juvenile mouse brain, as well as adult human brain, to map how epigenetic mechanisms control transcriptional phenotype and cell dynamics in tissue. Although highly concordant tissue features were identified by either spatial epigenome or spatial transcriptome we also observed distinct patterns, suggesting their differential roles in defining cell states. Linking epigenome to transcriptome pixel by pixel allows the uncovering of new insights in spatial epigenetic priming, differentiation and gene regulation within the tissue architecture. These technologies are of great interest in life science and biomedical research.
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| 34. |
- Zhang, Haiwen, et al.
(författare)
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Biologically inspired flexible photonic films for efficient passive radiative cooling
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:26, s. 14657-14666
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Tidskriftsartikel (refereegranskat)abstract
- Temperature is a fundamental parameter for all forms of lives. Natural evolution has resulted in organisms which have excellent thermoregulation capabilities in extreme climates. Bioinspired materials that mimic biological solution for thermoregulation have proven promising for passive radiative cooling. However, scalable production of artificial photonic radiators with complex structures, outstanding properties, high throughput, and low cost is still challenging. Herein, we design and demonstrate biologically inspired photonic materials for passive radiative cooling, after discovery of longicorn beetles' excellent thermoregulatory function with their dual-scale fluffs. The natural fluffs exhibit a finely structured triangular cross-section with two thermoregulatory effects which effectively reflects sunlight and emits thermal radiation, thereby decreasing the beetles' body temperature. Inspired by the finding, a photonic film consisting of a micropyramid-arrayed polymer matrix with random ceramic particles is fabricated with high throughput. The film reflects similar to 95% of solar irradiance and exhibits an infrared emissivity >0.96. The effective cooling power is found to be similar to 90.8 W center dot m(-2) and a temperature decrease of up to 5.1 degrees C is recorded under direct sunlight. Additionally, the film exhibits hydrophobicity, superior flexibility, and strong mechanical strength, which is promising for thermal management in various electronic devices and wearable products. Our work paves the way for designing and fabrication of high-performance thermal regulation materials.
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| 37. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 38. |
- Solmi, M, et al.
(författare)
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- 2022
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Ingår i: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299, s. 367-376
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Tidskriftsartikel (refereegranskat)
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