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CONCLUSION This study provides evidence of altered cortical activation in response to language tasks in patients after a laryngectomy compared with healthy volunteers, which may be considered brain plasticity in response to a laryngectomy.Separase, a cysteine endopeptidase, is a key player in mitotic sister chromatid separation, replication fork dynamics, and DNA repair. Aberrant expression and/or altered separase proteolytic activity are associated with aneuploidy, tumorigenesis, and disease progression. Since genomic instability and clonal evolution are hallmarks of progressing chronic myeloid leukemia (CML), we have comparatively examined separase proteolytic activity in TKI-treated chronic phase CML. Separase proteolytic activity was analyzed on single cell level in 88 clinical samples and in 14 healthy controls by a flow cytometric assay. In parallel, BCR-ABL1 gene expression and replication fork velocity were measured by qRT-PCR and DNA fiber assays, respectively. The separase activity distribution (SAD) value indicating the occurrence of MNCs with elevated separase proteolytic activity within samples was found to positively correlate with BCR-ABL1 gene expression levels and loss of MMR (relapse) throughout routine BCR-ABL1 monitoring. Analyses of CD34+ cells and MNCs fractionized by flow cytometric cell sorting according to their separase activity levels (H- and L-fractions) revealed that CD34+ cells with elevated separase activity levels (H-fractions) displayed enhanced proliferation/viability when compared with cells with regular (L-fraction) separase activity (mean 3.3-fold, p = 0.0011). BCR-ABL1 gene expression positivity prevailed in MNC H-fractions over L-fractions (42% vs. Tezacaftor nmr 8%, respectively). Moreover, expanding CD34+ cells of H-fractions showed decreased replication fork velocity compared with cells of L-fractions (p less then 0.0001). Our data suggests an association between high separase activity, residual BCR-ABL1 gene expression, and enhanced proliferative capacity in hematopoietic cells within the leukemic niche of TKI-treated chronic phase CML.Acute graft-versus-host disease (aGVHD) of the lower gastrointestinal (GI) tract is the major cause of non-relapse mortality (NRM) in allogeneic hematopoietic stem cell transplantation (alloHSCT). This study aimed to identify variables associated with corticosteroid response and NRM in patients who developed lower GI aGVHD. We retrospectively analyzed the clinical data of patients treated at Yonsei University Severance Hospital between 2008 and 2017. Among 244 recipients of alloHSCT, 48 (19.7%) were diagnosed as lower GI aGVHD at a median of 22 days after alloHSCT. In these cases, 20 (41.6%) patients were resistant to corticosteroid therapy. Corticosteroid resistance was associated with advanced stage of lower GI aGVHD (P = 0.019), low serum albumin (P = 0.006), and elevated CRP (P = 0.030) on day 7 after corticosteroid therapy. NRM rate was significantly higher in the corticosteroid-resistant group compared with the sensitive group (HR 5.339, P = 0.003). Multivariate analysis revealed serum albumin (P = 0.046), and CRP levels (P = 0.032) were independent prognostic factors for NRM. When the patients were classified into 3 groups according to Glasgow prognostic score (GPS), the rate of corticosteroid resistance was significantly higher in the high GPS group compared with the intermediate or low GPS group (83.3 vs. 27.2 and 15.3%, respectively, P less then 0.001). We demonstrated that low serum albumin and elevated CRP level on day 7 after corticosteroid therapy are objective biomarkers of corticosteroid resistance and a significant predictor for higher NRM. These simple and practical parameters could be valuable information predicting response and prognosis in lower GI aGVHD.In this study, the genome of a new strain of lytic Staphylococcus aureus Herelleviridae, vBSM-A1, was characterized and annotated. The phage was isolated from sewage samples collected in Xinjiang Province, China. The genome of vBSM-A1 was found to comprise a linear double-stranded DNA of 140,654 bp length, with a G + C content of 30.33%. A total of 215 ORFs were detected in the phage DNA, 74 of which were functionally assigned. The 3D structure model of endolysin LysK (ORF 143) was created using Phyre2.Autoinflammatory syndromes are characterized by an exaggerated activation of the innate immune system and frequently present with skin symptoms. In contrast to autoimmune disorders no specific autoantibodies or autoreactive immune cells are detected. Thus, the diagnosis is usually difficult and can only be made by a careful interpretation of anamnestic, clinical and laboratory parameters. In some hereditary autoimmune syndromes specific genetic mutations are described and can be helpful for the diagnosis. For treatment of these disorders both classic immunomodulatory drugs and specific cytokine inhibitors are used, mainly directed against interleukin‑1. Long-term therapy is generally required.Orphan genes, lacking detectable homologs in outgroup species, typically represent 10-30% of eukaryotic genomes. Efforts to find the source of these young genes indicate that de novo emergence from non-coding DNA may in part explain their prevalence. Here, we investigate the roots of orphan gene emergence in the Drosophila genus. Across the annotated proteomes of twelve species, we find 6297 orphan genes within 4953 taxon-specific clusters of orthologs. By inferring the ancestral DNA as non-coding for between 550 and 2467 (8.7-39.2%) of these genes, we describe for the first time how de novo emergence contributes to the abundance of clade-specific Drosophila genes. In support of them having functional roles, we show that de novo genes have robust expression and translational support. However, the distinct nucleotide sequences of de novo genes, which have characteristics intermediate between intergenic regions and conserved genes, reflect their recent birth from non-coding DNA. We find that de novo genes encode more disordered proteins than both older genes and intergenic regions. Together, our results suggest that gene emergence from non-coding DNA provides an abundant source of material for the evolution of new proteins. Following gene birth, gradual evolution over large evolutionary timescales moulds sequence properties towards those of conserved genes, resulting in a continuum of properties whose starting points depend on the nucleotide sequences of an initial pool of novel genes.
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