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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Gu, Jian, et al.
(författare)
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TGF-beta-Induced CD4(+) Foxp3(+) T Cells Attenuate Acute Graft-versus-Host Disease by Suppressing Expansion and Killing of Effector CD8(+) Cells
- 2014
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 193:7, s. 3388-3397
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Tidskriftsartikel (refereegranskat)abstract
- The use of TGF-beta-induced CD4(+) Foxp3(+) T cells (induced regulatory T cells [iTregs]) is an important prevention and treatment strategy in autoimmune diseases and other disorders. However, the potential use of iTregs as a treatment modality for acute graft-versus-host disease (aGVHD) has not been realized because they may be unstable and less suppressive in this disease. We restudied the ability of iTregs to prevent and treat aGVHD in two mouse models. Our results showed that, as long as an appropriate iTreg-generation protocol is used, these iTregs consistently displayed a potent ability to control aGVHD development and reduce mortality in the aGVHD animal models. iTreg infusion markedly suppressed the engraftment of donor CD8(+) cells and CD4(+) cells, the expression of granzyme A and B, the cytotoxic effect of donor CD8(+) cells, and the production of T cell cytokines in aGVHD. Therefore, we conclude that as long as the correct methods for generating iTregs are used, they can prevent and even treat aGVHD.
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| 5. |
- Wan, Cheng-Liang, et al.
(författare)
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基于玻璃毛细管的大气环境MeV质子微束的产生与测量 : [Production and measurement of MeV proton microbeams in atmospheric environment based on glass capillary]
- 2024
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Ingår i: Wuli xuebao. - 1000-3290. ; 73:10
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Tidskriftsartikel (refereegranskat)abstract
- 本文采用玻璃毛细管产生了大气环境中工作的2.5 MeV质子外束微束, 并对束斑直径及能量分布随玻璃毛细管与束流方向之间角度(倾角)变化进行测量. 测量结果表明, 在玻璃毛细管轴向与束流方向一致时(倾角为0°), 产生的微束中存在保持初始入射能量的直接穿透部分以及散射部分, 其中直接穿透的质子占比最大, 束斑直径也最大. 随着玻璃毛细管倾角的增大, 当其大于几何张角时, 束斑直径变小, 产生的微束全部为能量减小的散射部分, 直接穿透质子消失. 我们对质子在玻璃毛细管内传输时的内壁散射过程进行了模拟计算及离子轨迹分析, 发现大角度的散射部分决定了形成的外束微束斑外围轮廓, 而束斑中心区域由不与毛细管内壁产生任何作用的直接穿透离子构成, 其大小由玻璃毛细管出口直径以及几何容许张角决定. 采用玻璃毛细管产生的外束微束具有产生简单廉价, 微束区域定位简单的特点, 有望在辐射生物学、医学、材料等领域得到广泛应用.
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| 6. |
- Zhang, Qiong, et al.
(författare)
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Simulating the mid-Holocene, last interglacial and mid-Pliocene climate with EC-Earth3-LR
- 2021
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 14:2, s. 1147-1169
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Tidskriftsartikel (refereegranskat)abstract
- As global warming is proceeding due to rising greenhouse gas concentrations, the Earth system moves towards climate states that challenge adaptation. Past Earth system states are offering possible modelling systems for the global warming of the coming decades. These include the climate of the mid-Pliocene (similar to 3 Ma), the last interglacial (similar to 129-116 ka) and the mid-Holocene (similar to 6 ka). The simulations for these past warm periods are the key experiments in the Paleoclimate Model Intercomparison Project (PMIP) phase 4, contributing to phase 6 of the Coupled Model Intercomparison Project (CMIP6). Paleoclimate modelling has long been regarded as a robust out-of-sample test bed of the climate models used to project future climate changes. Here, we document the model setup for PMIP4 experiments with EC-Earth3-LR and present the large-scale features from the simulations for the mid-Holocene, the last interglacial and the mid-Pliocene. Using the pre-industrial climate as a reference state, we show global temperature changes, large-scale Hadley circulation and Walker circulation, polar warming, global monsoons and the climate variability modes - El Nino-Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO) and the Atlantic Multidecadal Oscillation (AMO). EC-Earth3-LR simulates reasonable climate responses during past warm periods, as shown in the other PMIP4-CMIP6 model ensemble. The systematic comparison of these climate changes in past three warm periods in an individual model demonstrates the model's ability to capture the climate response under different climate forcings, providing potential implications for confidence in future projections with the EC-Earth model.
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| 7. |
- Bai, Licheng, et al.
(författare)
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Explaining the Size Dependence in Platinum-Nanoparticle-Catalyzed Hydrogenation Reactions
- 2016
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 55:50, s. 15656-15661
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Tidskriftsartikel (refereegranskat)abstract
- Hydrogenation reactions are industrially important reactions that typically require unfavorably high H-2 pressure and temperature for many functional groups. Herein we reveal surprisingly strong size-dependent activity of Pt nanoparticles (PtNPs) in catalyzing this reaction. Based on unambiguous spectral analyses, the size effect has been rationalized by the size-dependent d-band electron structure of the PtNPs. This understanding enables production of a catalyst with size of 1.2 nm, which shows a sixfold increase in turnover frequency and 28-fold increase in mass activity in the regioselective hydrogenation of quinoline, compared with PtNPs of 5.3 nm, allowing the reaction to proceed under ambient conditions with unprecedentedly high reaction rates. The size effect and the synthesis strategy developed herein may provide a general methodology in the design of metal-nanoparticle-based catalysts for a broad range of organic syntheses.
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| 8. |
- Bondarenko, Vasyl, et al.
(författare)
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Structural Elucidation of Ivermectin Binding to α7nAChR and the Induced Channel Desensitization
- 2023
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society. - 1948-7193. ; 14:6, s. 1156-1165
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Tidskriftsartikel (refereegranskat)abstract
- The α7 nicotinic acetylcholine receptor (α7nAChR) mediates signaling in the central nervous system and cholinergic anti-inflammatory pathways. Ivermectin is a positive allosteric modulator of a full-length α7nAChR and an agonist of the α7nAChR construct containing transmembrane (TMD) and intracellular (ICD) domains, but structural insights of the binding have not previously been determined. Here, combining nuclear magnetic resonance as a primary experimental tool with Rosetta comparative modeling and molecular dynamics simulations, we have revealed details of ivermectin binding to the α7nAChR TMD + ICD and corresponding structural changes in an ivermectin-induced desensitized state. Ivermectin binding was stabilized predominantly by hydrophobic interactions from interfacial residues between adjacent subunits near the extracellular end of the TMD, where the inter-subunit gap was substantially expanded in comparison to the apo structure. The ion-permeation pathway showed a profile distinctly different from the resting-state profile but similar to profiles of desensitized α7nAChR. The ICD also exhibited structural changes, including reorientation of the MX and h3 helices relative to the channel axis. The resulting structures of the α7nAChR TMD + ICD in complex with ivermectin provide opportunities for discovering new modulators of therapeutic potential and exploring the structural basis of cytoplasmic signaling under different α7nAChR functional states.
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| 9. |
- Bondarenko, Vasyl, et al.
(författare)
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Structures of highly flexible intracellular domain of human alpha 7 nicotinic acetylcholine receptor
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The intracellular domain (ICD) of Cys-loop receptors mediates diverse functions. To date, no structure of a full-length ICD is available due to challenges stemming from its dynamic nature. Here, combining nuclear magnetic resonance (NMR) and electron spin resonance experiments with Rosetta computations, we determine full-length ICD structures of the human alpha 7 nicotinic acetylcholine receptor in a resting state. We show that similar to 57% of the ICD residues are in highly flexible regions, primarily in a large loop (loop L) with the most mobile segment spanning similar to 50 angstrom from the central channel axis. Loop L is anchored onto the MA helix and virtually forms two smaller loops, thereby increasing its stability. Previously known motifs for cytoplasmic binding, regulation, and signaling are found in both the helices and disordered flexible regions, supporting the essential role of the ICD conformational plasticity in orchestrating a broad range of biological processes.
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| 10. |
- de Miranda, Noel F. C. C., et al.
(författare)
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DNA repair genes are selectively mutated in diffuse large B cell lymphomas
- 2013
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 210:9, s. 1729-1742
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Tidskriftsartikel (refereegranskat)abstract
- DNA repair mechanisms are fundamental for B cell development, which relies on the somatic diversification of the immunoglobulin genes by V(D)J recombination, somatic hypermutation, and class switch recombination. Their failure is postulated to promote genomic instability and malignant transformation in B cells. By performing targeted sequencing of 73 key DNA repair genes in 29 B cell lymphoma samples, somatic and germline mutations were identified in various DNA repair pathways, mainly in diffuse large B cell lymphomas (DLBCLs). Mutations in mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite instability, increased number of somatic insertions/deletions, and altered mutation signatures in tumors. Somatic mutations in nonhomologous end-joining (NHEJ) genes (DCLRE1C/ARTEMIS, PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were identified in four DLBCL tumors and cytogenetic analyses revealed that translocations involving the immunoglobulin-heavy chain locus occurred exclusively in NHEJ-mutated samples. The novel mutation targets, CHEK2 and PARP1, were further screened in expanded DLBCL cohorts, and somatic as well as novel and rare germline mutations were identified in 8 and 5% of analyzed tumors, respectively. By correlating defects in a subset of DNA damage response and repair genes with genomic instability events in tumors, we propose that these genes play a role in DLBCL lymphomagenesis.
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