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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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- Kang, S, et al.
(författare)
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Are better existing WASH practices in urban slums associated with a lower long-term risk of severe cholera? A prospective cohort study with 4 years of follow-up in Mirpur, Bangladesh
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:9, s. e060858-
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the association between existing household water quality, sanitation and hygiene (WASH) practices and severe cholera risk in a dense urban slum where cholera is highly endemic.Design, setting and participantsWe assembled a large prospective cohort within a cluster randomised trial evaluating the effectiveness of oral cholera vaccine. Our dynamic cohort population (n=193 576) comprised individuals living in the ‘non-intervention’ clusters of the trial, and were followed over 4 years. This study was conducted in a dense urban slum community of Dhaka, Bangladesh and cholera surveillance was undertaken in 12 hospitals serving the study area.Primary outcome measureFirst severe cholera episode detected during follow-up period.MethodsWe applied a machine learning algorithm on a training subpopulation (n=96 943) to develop a binary (‘better’, ‘not better’) composite WASH variable predictive of severe cholera. The WASH rule was evaluated for performance in a separate validation subpopulation (n=96 633). Afterwards, we used Cox regression models to evaluate the association between ‘better’ WASH households and severe cholera risk over 4 years in the entire study population.ResultsThe ‘better’ WASH rule found that water quality and access were the most significant factors associated with severe cholera risk. Members of ‘better’ WASH households, constituting one-third of the population, had a 47% reduced risk of severe cholera (95% CI: 29 to 69; p<0.001), after adjusting for covariates. The protective association between living in a ‘better’ WASH household and severe cholera persisted in all age groups.ConclusionsSalutary existing household WASH practices were associated with a significantly reduced long-term risk of severe cholera in an urban slum of Dhaka. These findings suggest that WASH adaptations already practised in the community may be important for developing and implementing effective and sustainable cholera control programmes in similar settings.Trial registration numberThis article is a re-analysis of data from a cluster randomized trial; can be found on ClinicalTrials.govNCT01339845
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- Nie, M, et al.
(författare)
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PD-1/PD-L Pathway Potentially Involved in ITP Immunopathogenesis
- 2019
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Ingår i: Thrombosis and haemostasis. - : Georg Thieme Verlag KG. - 2567-689X .- 0340-6245. ; 119:5, s. 758-765
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Tidskriftsartikel (refereegranskat)abstract
- The binding of programmed death 1 (PD-1) to its ligands PD-L1 and PD-L2 on antigen-presenting cells turns off autoreactive T cells and induces peripheral tolerance. Aberrant PD-1/PD-L signalling could result in a breakdown of peripheral tolerance and lead to autoimmune diseases. In this study, we detected PD-1 and PD-L expression on T cells and dendritic cells (DCs) in immune thrombocytopenia (ITP) patients with active disease by flow cytometry. The effects of PD-L1-Fc fusion protein (PD-L1-Fc) on T cells and on secretion of interferon-γ (IFN-γ) and interleukin-2 (IL-2) were detected by flow cytometry and enzyme-linked immunosorbent assay, respectively. Compared with healthy controls, PD-1 expression was significantly increased in CD4+ T cells and CD8+ T cells from patients with active ITP. However, PD-L1 expression on monocyte-derived DCs was lower in patients with active ITP than in healthy controls. In vitro assays revealed that PD-L1-Fc increased T cell apoptosis, inhibited activation and proliferation of CD4+ T cells and CD8+ T cells and decreased IFN-γ and IL-2 secretion in patients with active ITP. These results suggest that the aberrant PD-1/PD-L negative co-stimulatory pathway may play a role in ITP. Enhancing PD-1/PD-L signalling might be a promising therapeutic approach for ITP patients by enhancing T cell apoptosis, inhibiting T cell activation and proliferation and reducing secretion of inflammatory factors.
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- Zhao, XX, et al.
(författare)
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Unraveling the magnetic carriers of igneous cores from the Atlantic, Pacific, and the southern Indian oceans with rock magnetic characterization
- 2006
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Ingår i: Physics of the Earth and Planetary Interiors. - : Elsevier BV. - 0031-9201. ; 156:3-4, s. 294-328
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Tidskriftsartikel (refereegranskat)abstract
- Previous rock magnetic investigations of oceanic basement samples have been mainly restricted by single drill holes of dredge collections. In this study, we present new and published data on the rock magnetic properties of igneous rock samples recovered during seven Ocean Drilling Program (ODP) legs in the Atlantic, Pacific, and the southern Indian oceans. The recovered igneous rocks from these legs are mainly basaltic flows (both submarine and subaerial), diabase sills, and serpentinized peridotites, with approximate ages of 140,000 years, 10-12, 34, 69, 100-108, and 110-121 Ma, which offers an opportunity to investigate magnetic properties and mineral changes attending alteration of basement rocks over a wide range of ages from variable tectonic settings. Titanomagnetite and titanomaghemite are commonly present in igneous rock samples of the Ontong Java Plateau, the Kerguelen Plateau/Broken Ridge, the eastern Equatorial Pacific, the middle Atlantic ridge (Trans-Atlantic Geotraverse area), and the Newfoundland-Iberia rifted margins. For basaltic rock samples, three general groups (A, B, and C, respectively) can be divided in terms of rock magnetic properties. Samples from group A have a single phase of Ti-poor titanomagnetite with Curie temperatures ranging between 480 and 580 degrees C and exhibit a strong Verwey transition in the vicinity of 110 K. Basalts from this group are most likely good paleomagnetic recorders and probably have preserved original and stable magnetic remanences. Group B is mainly observed in pillow lavas and is characterized by a Curie temperature of 260-280 degrees C, which is typical of low-temperature oxidized titanomaghemite or titanium rich titanomagnetite. The low-temperature curves for group B do not show the Verwey transition. Group C has more than one Curie temperature, which suggests the presence of multiple magnetic phases. The thermomagnetic signature indicates the inversion of titanomaghemite to a strongly magnetized magnetite, as shown by the irreversible cooling curves. For the serpentinized peridotites recovered from both sides of the Newfoundland-Iberia rifted margins, results from low-temperature measurements show that (titano)magnetites are present in the dark-colored peridotites, with a strong Verwey transition in the vicinity of 110 K, and with field- and frequency-dependent susceptibility curves that resemble those of synthetic TMO. In contrast to the magnetic properties observed from the dark-colored peridotites, the low-temperature curves for the yellow-brown-colored peridotites did not show any Verwey transition. Thermomagnetic analysis also failed to show evidence for titanomagnetites. The remanent magnetization is carried by a thermally unstable mineral that breaks down at about 420 degrees C, probably maghemite. The magnetic signatures of the serpentinized peridotites recovered from both sides of the Newfoundland-Iberia rift appear not in conflict with the notion that conjugate margins will have generally similar crustal structure and evolution history. Our rock magnetic data indicate that the differences in the rock magnetic properties of basaltic rocks are mainly a function of mineralogy and alteration. There is no apparent coincidence between the age of the rocks and the degree of low-temperature alteration, as suggested by the presence of nearly unoxidized titanomagnetite in the Cretaceous aged basalts and by an examination of Curie temperature versus sample age that does not unambiguously show a positive relationship between the degree of low-temperature oxidation and crust ages. (c) 206 Elsevier B.V. All rights reserved.
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