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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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- Gayou, O, et al.
(författare)
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Measurement of G(Ep)/G(Mp) in (e)over-right-arrowp -> e(p)over-right-arrow to Q(2)=5.6 GeV2
- 2002
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Ingår i: Physical Review Letters. - 1079-7114. ; 88:9
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Tidskriftsartikel (refereegranskat)abstract
- The ratio of the electric and magnetic form factors of the proton G(Ep)/G(Mp), which is an image of its charge and magnetization distributions, was measured at the Thomas Jefferson National Accelerator Facility (JLab) using the recoil polarization technique. The ratio of the form factors is directly proportional to the ratio of the transverse to longitudinal components of the polarization of the recoil proton in the elastic (e) over right arrowp --> e (p) over right arrow reaction. The new data presented span the range 3.5 < Q(2) < 5.6 GeV2 and are well described by a linear Q(2) fit. Also, the ratio rootQ(2) F-2p/F-1p reaches a constant value above Q(2) = 2 GeV2.
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- Lu, WS, et al.
(författare)
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PDGFD switches on stem cell endothelial commitment
- 2022
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Ingår i: Angiogenesis. - : Springer Science and Business Media LLC. - 1573-7209 .- 0969-6970. ; 25:4, s. 517-533
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Tidskriftsartikel (refereegranskat)abstract
- The critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related genes in ESCs. Importantly, PDGFD genetic deletion or knockdown increases ESC self-renewal and decreases blood vessel densities in both embryonic and neonatal mice and in teratomas. Mechanistically, we reveal that PDGFD fulfills this function via the MAPK/ERK pathway. Our findings provide new insight of PDGFD as a novel regulator of ESC fate determination, and suggest therapeutic implications of modulating PDGFD activity in stem cell therapy.
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- Lv, WJ, et al.
(författare)
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A High Serum Phosphate and Calcium-Phosphate Product Is Associated With Cerebral Small Vascular Disease in Patients With Stroke: A Real-World Study
- 2022
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Ingår i: Frontiers in nutrition. - : Frontiers Media SA. - 2296-861X. ; 9, s. 801667-
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral small vessel disease (CSVD) is a slowly progressive disease, often accompanied by stroke, and results in dementia, depression, and cognitive impairment. It was already known that calcium and phosphorus metabolism (CPM) disorders were associated with vascular-related adverse events. The risk factors of CSVD and the relationship between serum calcium (Ca), phosphorus (P), calcium-phosphate product (Ca × P), and CSVD in patients with stroke without CPM disorders are still obscure. In our study, 528 patients with stroke without CPM disorders were enrolled in a cohort from a consecutive hospital-based stroke registry, with 488 patients with CSVD as cases and 140 without CSVD as controls. The patients with CSVD were further sub-grouped into lacunes, white matter hyperintensities (WMHs), and cerebral microbleeds (CMBs). By applying univariate and multivariate logistic regression analysis, the following novel findings were obtained: (i) up to 76.19% of patients with stroke had signs of CSVD, and lacunes are the most common subtype. Notably, 22.96% of patients with CSVD had multiple subtypes coexisted. (ii) Compared with patients without CSVD, patients with CSVD had higher levels of age, rate of hypertension or diabetes, serum Ca, P, Ca × P, and lower levels of white blood cell (WBC) and hemoglobin (HB). (iii) We developed 2 predictive models and nomograms for predicting CSVD, in addition to the known factors (age and hypertension). The levels of P and Ca × P were positively correlated with the risk of CSVD (P: OR = 3,720.401, 95% CI (646.665–21,404.249); Ca × P: OR = 1.294, 95% CI (1.222–1.370)). (iv) The models were further validated in subtypes of CSVD, including lacunes, WMHs, and CMBs, and the results were still valid among the subtypes. In summary, CSVD was highly prevalent in patients with stroke, and high serum P and Ca × P are potential risk factors of CSVD and all subtypes including lacunes, WMHs, and CMBs.
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- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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