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DURING replication of RNA tumour viruses, the genetic information contained in the viral RNA seems to be transferred to DNA1,2. Studies on the enzymatic activities present in the virus particles suggest that this transfer is mediated by an RNA dependent DNA polymerase3,4. RNA-DNA hybrids have been demonstrated to occur as intermediates in this reaction5 and single stranded DNA is generated as an early reaction product6, which is then replicated to give a double stranded DNA product6–8. The mechanism by which the single stranded DNA is displaced from the RNA template is, however, not known.  相似文献   
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Background

Although a preponderance of pre-clinical data demonstrates the immunosuppressive potential of mesenchymal stromal cells (MSCs), significant heterogeneity and lack of critical quality attributes (CQAs) based on immunosuppressive capacity likely have contributed to inconsistent clinical outcomes. This heterogeneity exists not only between MSC lots derived from different donors, tissues and manufacturing conditions, but also within a given MSC lot in the form of functional subpopulations. We therefore explored the potential of functionally relevant morphological profiling (FRMP) to identify morphological subpopulations predictive of the immunosuppressive capacity of MSCs derived from multiple donors, manufacturers and passages.

Methods

We profiled the single-cell morphological response of MSCs from different donors and passages to the functionally relevant inflammatory cytokine interferon (IFN)-γ. We used the machine learning approach visual stochastic neighbor embedding (viSNE) to identify distinct morphological subpopulations that could predict suppression of activated CD4+ and CD8+ T cells in a multiplexed quantitative assay.

Results

Multiple IFN-γ–stimulated subpopulations significantly correlated with the ability of MSCs to inhibit CD4+ and CD8+ T-cell activation and served as effective CQAs to predict the immunosuppressive capacity of additional manufactured MSC lots. We further characterized the emergence of morphological heterogeneity following IFN-γ stimulation, which provides a strategy for identifying functional subpopulations for future single-cell characterization and enrichment techniques.

Discussion

This work provides a generalizable analytical platform for assessing functional heterogeneity based on single-cell morphological responses that could be used to identify novel CQAs and inform cell manufacturing decisions.  相似文献   
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1. Ecotypes may arise following allopatric separation from source populations. The simultaneous transfer of an exotic plant to a novel environment, along with its stenophagous herbivore, may complicate more traditional patterns of divergence from the plant and insect source populations. 2. The present study evaluated herbivory effects by two Cyrtobagous salviniae ecotypes on two species of Salvinia: the larger S. molesta and the smaller S. minima. Evaluations were based on relative growth rates, biomass production, coverage, and nutrient cycling in a series of complementary and comparative laboratory and outdoor tank experiments. 3. In general, the experiment results indicated that the smaller Florida ecotype of C. salviniae impacted both Salvinia species more than the larger Brazil ecotype. Herbivory, especially by the Florida ecotype, also improved water quality and accelerated nutrient cycling by increasing the rates of litterfall from the standing crops of salvinia. 4. The smaller size of the Florida ecotype may be adaptive by allowing maximal exploitation of host plants via internal larval feeding, which presumably reduces predation risk while increasing damage to the plant. These findings provide support for relying on the suppressive effects of the Florida ecotype in Florida, rather than introducing the Brazil ecotype to counter new infestations of S. molesta.  相似文献   
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trovik c. s., bauer h. c. f., brosjö o., skoog l. and söderlund v. (1998) Cytopathology 9, 320–328
Fine needle aspiration (FNA) cytology in the diagnosis of recurrent soft tissue sarcoma
We have used FNA cytology to diagnose suspected local recurrences of soft tissue sarcoma. Since 1991, a total of 95 FNA cytologies were performed on 86 patients. There were 47 local recurrences, of which 44 were diagnosed correctly by FNA cytology; one biopsy was inconclusive, and two lesions were incorrectly assessed as benign. Thirty-nine patients proved to have benign lesions in the scar area examined cytologically on 50 occasions. None of the specimens was regarded as malignant, but in four cases FNA cytology was inconclusive. Overall, there were 5% inconclusive cytological biopsies, 0% falsely malignant and 5% falsely benign. The inconclusive and false-negative cytological diagnoses had no important clinical consequences. FNA biopsy provides a simple means of diagnosing local recurrence of soft tissue sarcoma.  相似文献   
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