Highlightsd Ski complex mediated RNA degradation is required in the germline for fertility.d A subset of early oogenic RNAs are degraded concurrent with oocyte specification.d Early oogenic RNAs are degraded utilizing components of the No Go Decay pathway.d Degradation of early oogenic RNAs is required for maintenance of oocyte fate.
BackgroundSaccharomyces boulardii is a probiotic yeast routinely used to prevent and to treat gastrointestinal disorders, including the antibiotic-associated diarrhea caused by Clostridium difficile infections. However, only 1-3% of the yeast administered orally is recovered alive in the feces suggesting that this yeast is unable to survive the acidic environment of the gastrointestinal tract.ResultsWe provide evidence that suggests that S. boulardii undergoes programmed cell death (PCD) in acidic environments, which is accompanied by the generation of reactive oxygen species and the appearance of caspase-like activity. To better understand the mechanism of cell death at the molecular level, we generated microarray gene expression profiles of S. boulardii cells cultured in an acidic environment. Significantly, functional annotation revealed that the up-regulated genes were significantly over-represented in cell death pathways Finally, we show that S-adenosyl-L-methionine (AdoMet), a commercially available, FDA-approved dietary supplement, enhances the viability of S. boulardii in acidic environments, most likely by preventing programmed cell death.ConclusionsIn toto, given the observation that many of the proven health benefits of S. boulardii are dependent on cell viability, our data suggests that taking S. boulardii and AdoMet together may be a more effective treatment for gastrointestinal disorders than taking the probiotic yeast alone.
After fertilization, maternally contributed factors to the egg initiate the transition to pluripotency to give rise to embryonic stem cells, in large part by activating de novo transcription from the embryonic genome. Diverse mechanisms coordinate this transition across animals, suggesting that pervasive regulatory remodeling has shaped the earliest stages of development. Here, we show that maternal homologs of mammalian pluripotency reprogramming factors OCT4 and SOX2 divergently activate the two subgenomes of Xenopus laevis, an allotetraploid that arose from hybridization of two diploid species ~18 million years ago. Although most genes have been retained as two homeologous copies, we find that a majority of them undergo asymmetric activation in the early embryo. Chromatin accessibility profiling and CUT&RUN for modified histones and transcription factor binding reveal extensive differences in enhancer architecture between the subgenomes, which likely arose through genomic disruptions as a consequence of allotetraploidy. However, comparison with diploid X. tropicalis and zebrafish shows broad conservation of embryonic gene expression levels when divergent homeolog contributions are combined, implying strong selection to maintain dosage in the core vertebrate pluripotency transcriptional program, amid genomic instability following hybridization.
Genetic reduction is of great significance in many biological pathways. In particular, aneuploid cancerous cells typically undergo genetic reduction to obtain a diploid state, a process accompanied by apoptotic programmed cell death. A tetraploid strain of Candida albicans, when grown on a diploid specific pre‐sporulation media, undergoes random chromosome loss, becoming diploid to near‐diploid in DNA content and undergoing significant cell death as part of the completion of a parasexual cycle. Cell death measurements were made for cells grown on pre‐sporulation media plates. Measurements of viability were made with a methylene blue stain, showing significantly lower tetraploid viability. Assays done to determine levels of reactive oxygen species present showed increased concentration in tetraploid cells undergoing genome reduction. Similar results were found in an assay for caspase These results indicate high ROS levels and high levels of caspase activity in the reducing tetraploid, suggestive of apoptosis‐like programmed cell death accompanying genome reduction. Similar results are seen in diploid Saccharomyces cerevisiae. Further research is currently being done with both tetraploid and diploid strands with apoptotic gene knockouts to further understand the mechanism of death, and understanding of these results could aid in understanding of cancerous and other biological mechanisms in humans.
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