TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Chromatin epigenetics participate in control of gene expression during metazoan development. DNA methylation and post-translational modifications (PTMs) of histones have been extensively characterised in cell types present in, or derived from, mouse embryos. In embryonic stem cells (ESCs) derived from blastocysts, factors involved in deposition of epigenetic marks regulate properties related to self-renewal and pluripotency. In the germ lineage, changes in histone PTMs and DNA demethylation occur during formation of the primordial germ cells (PGCs) to reset the epigenome of the future gametes. Trimethylation of histone H3 on lysine 27 (H3K27me3) by Polycomb group proteins is involved in several epigenome-remodelling steps, but it remains unclear whether these epigenetic features are conserved in non-mammalian vertebrates. To investigate this question, we compared the abundance and nuclear distribution of the main histone PTMs, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in chicken ESCs, PGCs and blastodermal cells (BCs) with differentiated chicken ESCs and embryonic fibroblasts. In addition, we analysed the expression of chromatin modifier genes to better understand the establishment and dynamics of chromatin epigenetic profiles.', 'The nuclear distributions of most PTMs and 5hmC in chicken stem cells were similar to what has been described for mammalian cells. However, unlike mouse pericentric heterochromatin (PCH), chicken ESC PCH contained high levels of trimethylated histone H3 on lysine 27 (H3K27me3). In differentiated chicken cells, PCH was less enriched in H3K27me3 relative to chromatin overall. In PGCs, the H3K27me3 global level was greatly reduced, whereas the H3K9me3 level was elevated. Most chromatin modifier genes known in mammals were expressed in chicken ESCs, PGCs and BCs. Genes presumably involved in de novo DNA methylation were very highly expressed. DNMT3B and HELLS/SMARCA6 were highly expressed in chicken ESCs, PGCs and BCs compared to differentiated chicken ESCs and embryonic fibroblasts, and DNMT3A was strongly expressed in ESCs, differentiated ESCs and BCs.\Question: Do chicken embryonic stem cells and primordial germ cells display different heterochromatic histone marks than their mammalian counterparts?

SOLUTION: Chicken ESCs and PGCs differ from their mammalian counterparts with respect to H3K27 methylation. High enrichment of H3K27me3 at PCH is specific to pluripotent cells in chicken. Our results demonstrate that the dynamics in chromatin constitution described during mouse development is not universal to all vertebrate species.

PROBLEM: Context: Cicatricial alopecia is a form of hair loss that causes both cosmetic and psychological concerns. Although tissue expanders are the common approach to reconstruction, no algorithm exists in the literature for this process. In this study, it was aimed to create an algorithm for the reconstruction of lateral scalp alopecias with the goal to achieve better and standardized results.', 'Lateral scalp alopecias were divided into three groups: total lateral alopecia (type I), temporal and sideburn alopecia (type II), and sideburn alopecia (type III). Tissue expanders were placed at the parieto-occipital area in type I defects, parietal area in type II defects, and the temporal region in type III defects. Tissue expanders were used to create flaps that were advanced with 60° rotation, 90° rotation, and no rotation for type I, II, and III defects, respectively.', 'Fifteen patients were treated with this algorithm. Using this simple approach, we achieved natural, standardized aesthetic results for each patient, all of whom were satisfied with the final results.\Question: Do our experiences on the reconstruction of lateral scalp burn alopecia with tissue expanders?

SOLUTION: Although the number of case were limited, the ideal and standardized cosmetic results could be obtained by this approach.

PROBLEM: Context: Alternative splicing is important for increasing the complexity of the human proteome from a limited genome. Previous studies have shown that for some autoantigens, there is differential immunogenicity among alternatively spliced isoforms.', 'Herein, we tested the hypothesis that alternative splicing is a common feature for transcripts of autologous proteins that are autoantigens. The corollary hypothesis tested was that nonautoantigen transcripts have a lower frequency of alternative splicing.', 'The extent of alternative splicing within 45 randomly selected self-proteins associated with autoimmune diseases was compared with 9554 randomly selected proteins in the human genome by using bioinformatics analyses. Isoform-specific regions that resulted from alternative splicing were studied for their potential to be epitopes for antibodies or T-cell receptors.', 'Alternative splicing occurred in 100% of the autoantigen transcripts. This was significantly higher than the approximately 42% rate of alternative splicing observed in the 9554 randomly selected human gene transcripts ( P < .001). Within the isoform-specific regions of the autoantigens, 92% and 88% encoded MHC class I and class II-restricted T-cell antigen epitopes, respectively, and 70% encoded antibody binding domains. Furthermore, 80% of the autoantigen transcripts underwent noncanonical alternative splicing, which is also significantly higher than the less than 1% rate in randomly selected gene transcripts ( P < .001).\Question: Does increased noncanonical splicing of autoantigen transcripts provide the structural basis for expression of untolerized epitopes?

SOLUTION:
These studies suggest that noncanonical alternative splicing may be an important mechanism for the generation of untolerized epitopes that may lead to autoimmunity. Furthermore, the product of a transcript that does not undergo alternative splicing is unlikely to be a target antigen in autoimmunity.