227 research outputs found

    Biphasic regulation of the transcription factor ABORTED MICROSPORES (AMS) is essential for tapetum and pollen development in Arabidopsis

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    Viable pollen is essential for plant reproduction and crop yield. Its production requires coordinated expression at specific stages during anther development, involving early meiosis-associated events and late pollen wall formation. The ABORTED MICROSPORE (AMS) transcription factor is a master regulator of sporopollenin biosynthesis, secretion and pollen wall formation in Arabidopsis. Here we show it has complex regulation and additional essential roles earlier in pollen formation. • An inducible-AMS reporter was created for functional rescue, protein expression pattern analysis and to distinguish between direct and indirect targets. Mathematical modelling was used to create regulatory networks based on wildtype RNA and protein expression. • Dual activity of AMS was defined by biphasic protein expression in anther tapetal cells, with an initial peak around pollen meiosis and then later during pollen wall development. Direct AMS-regulated targets exhibit temporal regulation, indicating additional factors are associated with their regulation. • We demonstrate that AMS biphasic expression is essential for pollen development and defines distinct functional activities during early and late pollen development. Mathematical modelling suggests AMS may competitively form a protein complex with other tapetum-expressed transcription factors, and that biphasic regulation is due to repression of upstream regulators and promotion of AMS protein degradation

    Grafted c-kit+/SSEA1− eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses

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    Abstract Background Despite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry. Methods Eye-wall c-kit+/stage-specific embryonic antigen 1 (SSEA1)− cells were isolated via fluorescence-activated cell sorting, and their self-renewal and differentiation potential were detected by immunochemistry and flow cytometry in vitro. After labeling with quantum nanocrystal dots and transplantation into the subretinal space of rd1 RD mice, differentiation and synapse formation by daughter cells of the eye-wall c-kit+/SSEA1− cells were evaluated by immunochemistry and western blotting. Morphological changes of the inner retina of rd1 mice after cell transplantation were demonstrated by immunochemistry. Retinal function of rd1 mice that received cell grafts was tested via flash electroretinograms and the light/dark transition test. Results Eye-wall c-kit+/SSEA1− cells were self-renewing and clonogenic, and they retained their proliferative potential through more than 20 passages. Additionally, eye-wall c-kit+/SSEA1− cells were capable of differentiating into multiple retinal cell types including photoreceptors, bipolar cells, horizontal cells, amacrine cells, Müller cells, and retinal pigment epithelium cells and of transdifferentiating into smooth muscle cells and endothelial cells in vitro. The levels of synaptophysin and postsynaptic density-95 in the retinas of eye-wall c-kit+/SSEA1− cell-transplanted rd1 mice were significantly increased at 4 weeks post transplantation. The c-kit+/SSEA1− cells were capable of differentiating into functional photoreceptors that formed new synaptic connections with recipient retinas in rd1 mice. Transplantation also partially corrected the abnormalities of inner retina of rd1 mice. At 4 and 8 weeks post transplantation, the rd1 mice that received c-kit+/SSEA1− cells showed significant increases in a-wave and b-wave amplitude and the percentage of time spent in the dark area. Conclusions Grafted c-kit+/SSEA1− cells restored the retinal function of rd1 mice via regulating neural plasticity and forming new graft-to-host synapses. </jats:sec

    Preliminary analysis of cervical cancer immunotherapy

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    Cervical cancer is one of the most common gynecologically malignancies worldwide. Although vaccine and cervical cancer screening including human papillomavirus testing, cytology testing, and colposcopy have developed rapidly in recent years, effectively reducing cervical cancer mortality, cervical cancer remains a malignancy with higher female fatality rates worldwide and has a high risk for socioeconomically disadvantaged groups. The combination of platinum-paclitaxel and chemotherapy, possibly with the addition of bevacizumab, is currently the treatment of choice for advanced cervical cancer, but it only has remission purposes. Therefore, new therapeutic strategies are needed for both locally advanced and metastatic cervical cancer. Here, we make a preliminary analysis of cervical cancer immunotherapy

    Gasdermin: a novel therapeutic target for tumour treatment by activating anti-tumour immunity

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    Age-induced changes in lung microenvironment: from melanoma dormancy to outgrowth

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    Age-induced changes in lung microenvironment: from melanoma dormancy to outgrowth

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