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151.
Tropea KA Leder E Aslam M Lau AN Raiser DM Lee JH Balasubramaniam V Fredenburgh LE Alex Mitsialis S Kourembanas S Kim CF 《American journal of physiology. Lung cellular and molecular physiology》2012,302(9):L829-L837
Bronchopulmonary dysplasia (BPD) remains a major complication of prematurity resulting in significant morbidity and mortality. The pathology of BPD is multifactorial and leads to alveolar simplification and distal lung injury. Previous studies have shown a beneficial effect of systemic treatment with bone marrow-derived mesenchymal stromal cells (MSCs) and MSC-conditioned media (MSC-CM) leading to amelioration of the lung parenchymal and vascular injury in vivo in the hyperoxia murine model of BPD. It is possible that the beneficial response from the MSCs is at least in part due to activation of endogenous lung epithelial stem cells. Bronchioalveolar stem cells (BASCs) are an adult lung stem cell population capable of self-renewal and differentiation in culture, and BASCs proliferate in response to bronchiolar and alveolar lung injury in vivo. Systemic treatment of neonatal hyperoxia-exposed mice with MSCs or MSC-CM led to a significant increase in BASCs compared with untreated controls. Treatment of BASCs with MSC-CM in culture showed an increase in growth efficiency, indicating a direct effect of MSCs on BASCs. Lineage tracing data in bleomycin-treated adult mice showed that Clara cell secretory protein-expressing cells including BASCs are capable of contributing to alveolar repair after lung injury. MSCs and MSC-derived factors may stimulate BASCs to play a role in the repair of alveolar lung injury found in BPD and in the restoration of distal lung cell epithelia. This work highlights the potential important role of endogenous lung stem cells in the repair of chronic lung diseases. 相似文献
152.
Rice straw burning has accompanied paddy management for millennia, introducing black carbon (BC) into soil as the residue of incomplete combustion. This study examined the contribution of BC to soil organic matter and the rate at which it accumulates in paddy soils as a result of prolonged paddy management. Soil depth profiles were sampled along a chronosequence of 0–2000 years of rice–wheat rotation systems and adjacent non‐paddy systems (50–700 years) in the Bay of Hangzhou (Zhejiang province, China). The soil BC content and its degree of condensation were assessed using benzene‐polycarboxylic acids (BPCAs) as geochemical markers. The results showed that despite regular long term BC input, BC only contributed 7–11% of total soil organic carbon (SOC) in the topsoil horizons. Nevertheless, along with SOC, paddy soils accumulated BC with increasing duration of management until 297 years to reach a steady‐state of 13 t BC ha?1. This was 1.8 times more than in non‐paddy soils. The fate of BC in paddy soils (0–1 m) could be modeled revealing an average annual input of 44 kg ha?1 yr?1, and a mean residence time of 303 years. The subsoils contributed at least 50% to overall BC stocks, which likely derived from periods prior to land embankment and episodic burial of ancient topsoil, as also indicated by BPCA pattern changes. We conclude that there is a significant but limited accumulation of C in charred forms upon prolonged paddy management. The final contribution of BC to total SOC in paddy soils was similar to that in other aerobic ecosystems of the world. 相似文献
153.
Complex multimeric recombinant proteins such as therapeutic antibodies require a eukaryotic expression system. Transgenic
plants may serve as promising alternatives to the currently favored mammalian cell lines or hybridomas. In contrast to prokaryotic
systems, posttranslational modifications of plant and human proteins resemble each other largely, among those, protein N-glycosylation
of the complex type. However, a few plant-specific sugar residues may cause immune reactions in humans, representing an obstacle
for the broad use of plant-based systems as biopharmaceutical production hosts. The moss Physcomitrella patens represents a flexible tissue-culture system for the contained production and secretion of recombinant biopharmaceuticals
in photobioreactors. The recent synthesis of therapeutic proteins as a scFv antibody fragment or the large and heavily modified
complement regulator factor H demonstrate the versatility of this expression system. A uniquely efficient gene targeting mechanism
can be employed to precisely engineer the glycosylation machinery for recombinant products. In this way, P. patens lines with non-immunogenic optimized glycan structures were created. Therapeutic antibodies produced in these strains exhibited
antibody-dependent cellular cytotoxicity superior to the same molecules synthesized in mammalian cell lines. 相似文献
154.
Sprick MR Rieser E Stahl H Grosse-Wilde A Weigand MA Walczak H 《The EMBO journal》2002,21(17):4520-4530
The involvement of the death adaptor protein FADD and the apoptosis-initiating caspase-8 in CD95 and TRAIL death signalling has recently been demonstrated by the analysis of the native death-inducing signalling complex (DISC) that forms upon ligand-induced receptor cross-linking. However, the role of caspase-10, the other death-effector-domain-containing caspase besides caspase-8, in death receptor signalling has been controversial. Here we show that caspase-10 is recruited not only to the native TRAIL DISC but also to the native CD95 DISC, and that FADD is necessary for its recruitment to and activation at these two protein complexes. With respect to the function of caspase-10, we show that it is not required for apoptosis induction. In addition, caspase-10 can not substitute for caspase-8, as the defect in apoptosis induction observed in caspase-8-deficient cells could not be rescued by overexpression of caspase-10. Finally, we demonstrate that caspase-10 is cleaved during CD95-induced apoptosis of activated T cells. These results show that caspase-10 activation occurs in primary cells, but that its function differs from that of caspase-8. 相似文献
155.
156.
Jye-Lin Hsu Dick J. H. van den Boomen Peter Tomasec Michael P. Weekes Robin Antrobus Richard J. Stanton Eva Ruckova Daniel Sugrue Gavin S. Wilkie Andrew J. Davison Gavin W. G. Wilkinson Paul J. Lehner 《PLoS pathogens》2015,11(4)
Human cytomegalovirus (HCMV) US2, US3, US6 and US11 act in concert to prevent immune recognition of virally infected cells by CD8+ T-lymphocytes through downregulation of MHC class I molecules (MHC-I). Here we show that US2 function goes far beyond MHC-I degradation. A systematic proteomic study using Plasma Membrane Profiling revealed US2 was unique in downregulating additional cellular targets, including: five distinct integrin α-chains, CD112, the interleukin-12 receptor, PTPRJ and thrombomodulin. US2 recruited the cellular E3 ligase TRC8 to direct the proteasomal degradation of all its targets, reminiscent of its degradation of MHC-I. Whereas integrin α-chains were selectively degraded, their integrin β1 binding partner accumulated in the ER. Consequently integrin signaling, cell adhesion and migration were strongly suppressed. US2 was necessary and sufficient for degradation of the majority of its substrates, but remarkably, the HCMV NK cell evasion function UL141 requisitioned US2 to enhance downregulation of the NK cell ligand CD112. UL141 retained CD112 in the ER from where US2 promoted its TRC8-dependent retrotranslocation and degradation. These findings redefine US2 as a multifunctional degradation hub which, through recruitment of the cellular E3 ligase TRC8, modulates diverse immune pathways involved in antigen presentation, NK cell activation, migration and coagulation; and highlight US2’s impact on HCMV pathogenesis. 相似文献
157.
158.
Tereza Krejcova Miroslava Smelcova Jaroslav Petr Jean-Francois Bodart Marketa Sedmikova Jan Nevoral Marketa Dvorakova Alena Vyskocilova Ivona Weingartova Veronika Kucerova-Chrpova Eva Chmelikova Lenka Tumova Frantisek Jilek 《PloS one》2015,10(1)
Porcine oocytes that have matured in in vitro conditions undergo the process of aging during prolonged cultivation, which is manifested by spontaneous parthenogenetic activation, lysis or fragmentation of aged oocytes. This study focused on the role of hydrogen sulfide (H2S) in the process of porcine oocyte aging. H2S is a gaseous signaling molecule and is produced endogenously by the enzymes cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MPST). We demonstrated that H2S-producing enzymes are active in porcine oocytes and that a statistically significant decline in endogenous H2S production occurs during the first day of aging. Inhibition of these enzymes accelerates signs of aging in oocytes and significantly increases the ratio of fragmented oocytes. The presence of exogenous H2S from a donor (Na2S.9H2O) significantly suppressed the manifestations of aging, reversed the effects of inhibitors and resulted in the complete suppression of oocyte fragmentation. Cultivation of aging oocytes in the presence of H2S donor positively affected their subsequent embryonic development following parthenogenetic activation. Although no unambiguous effects of exogenous H2S on MPF and MAPK activities were detected and the intracellular mechanism underlying H2S activity remains unclear, our study clearly demonstrates the role of H2S in the regulation of porcine oocyte aging. 相似文献
159.
160.