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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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- Chen, JM, et al.
(författare)
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Increased serum levels of interleukin-18, -23 and -17 in Chinese patients with Alzheimer's disease
- 2014
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 38:5-6, s. 321-329
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Aims:</i></b> To evaluate the serum levels of interleukin (IL)-18, IL-23 and IL-17 in Chinese patients with Alzheimer's disease (AD), and explore correlations between the three cytokines and relevant parameters. <b><i>Methods:</i></b> Serum concentrations of IL-18, IL-23 and IL-17 were measured by ELISA for 53 AD patients and 53 sex- and age-matched healthy controls in a community of elderly individuals in a Shanghai suburb. <b><i>Results:</i></b> Serum concentrations of IL-18, IL-23 and IL-17 were significantly higher in AD patients than controls. The serum level of IL-23 was observed to be significantly higher (p = 0.049) in female AD patients than male AD patients. In addition, a significantly inverse correlation was found between IL-18 and MMSE score (r<sub>s</sub> = -0.356, p = 0.011) for all AD patients. <b><i>Conclusion:</i></b> Elevated IL-18, IL-23 and IL-17 levels are observed in AD patients and differences may exist between males and females. Besides, IL-18 may correlate with the severity of AD.
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- Tang, BW, et al.
(författare)
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Occupational inhalable agents constitute major risk factors for rheumatoid arthritis, particularly in the context of genetic predisposition and smoking
- 2023
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 82:3, s. 316-323
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Tidskriftsartikel (refereegranskat)abstract
- To assess the effects of occupational inhalable exposures on rheumatoid arthritis (RA) development and their interactions with smoking and RA-risk genes, stratifying by presence of anticitrullinated protein antibodies (ACPA).MethodsData came from the Swedish Epidemiological Investigation of RA, consisting of 4033 incident RA cases and 6485 matched controls. Occupational histories were retrieved, combining with a Swedish national job-exposure matrix, to estimate exposure to 32 inhalable agents. Genetic data were used to define Genetic Risk Score (GRS) or carrying any copy of human leucocyte antigen class II shared epitope (HLA-SE) alleles. Associations were identified with unconditional logistical regression models. Attributable proportion due to interaction was estimated to evaluate presence of interaction.ResultsExposure to any occupational inhalable agents was associated with increased risk for ACPA-positive RA (OR 1.25, 95% CI 1.12 to 1.38). The risk increased as number of exposed agents increased (Ptrend<0.001) or duration of exposure elongated (Ptrend<0.001). When jointly considering exposure to any occupational inhalable agents, smoking and high GRS, a markedly elevated risk for ACPA-positive RA was observed among the triple-exposed group compared with those not exposed to any (OR 18.22, 95% CI 11.77 to 28.19). Significant interactions were found between occupational inhalable agents and smoking/genetic factors (high GRS or HLA-SE) in ACPA-positive RA.ConclusionsOccupational inhalable agents could act as important environmental triggers in RA development and interact with smoking and RA-risk genes leading to excessive risk for ACPA-positive RA. Future studies are warranted to assess preventive strategies aimed at reducing occupational hazards and smoking, especially among those who are genetically vulnerable.
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