Houseflies provide a good experimental model to study the initial evolutionary stages of a primary sex-determining locus because they possess different recently evolved proto-Y chromosomes that contain male-determining loci (M) with the same male-determining gene, Mdmd. We investigate M-loci genomically and cytogenetically revealing distinct molecular architectures among M-loci. M on chromosome V (M) has two intact Mdmd copies in a palindrome.
View Article and Find Full Text PDFPurpose: Target-dependent TCB activity can result in the strong and systemic release of cytokines that may develop into cytokine release syndrome (CRS), highlighting the need to understand and prevent this complex clinical syndrome.
Experimental Design: We explored the cellular and molecular players involved in TCB-mediated cytokine release by single-cell RNA-sequencing of whole blood treated with CD20-TCB together with bulk RNA-sequencing of endothelial cells exposed to TCB-induced cytokine release. We used the in vitro whole blood assay and an in vivo DLBCL model in immunocompetent humanized mice to assess the effects of dexamethasone, anti-TNFα, anti-IL6R, anti-IL1R, and inflammasome inhibition, on TCB-mediated cytokine release and antitumor activity.
Computational methods represent the lifeblood of modern molecular biology. Benchmarking is important for all methods, but with a focus here on computational methods, benchmarking is critical to dissect important steps of analysis pipelines, formally assess performance across common situations as well as edge cases, and ultimately guide users on what tools to use. Benchmarking can also be important for community building and advancing methods in a principled way.
View Article and Find Full Text PDFContinuity, correctness, and completeness of genome assemblies are important for many biological projects. Long reads represent a major driver towards delivering high-quality genomes, but not everybody can achieve the necessary coverage for good long read-only assemblies. Therefore, improving existing assemblies with low-coverage long reads is a promising alternative.
View Article and Find Full Text PDFIn high-throughput sequencing data, performance comparisons between computational tools are essential for making informed decisions at each step of a project. Simulations are a critical part of method comparisons, but for standard Illumina sequencing of genomic DNA, they are often oversimplified, which leads to optimistic results for most tools. ReSeq improves the authenticity of synthetic data by extracting and reproducing key components from real data.
View Article and Find Full Text PDFIn insects, rapidly evolving primary sex-determining signals are transduced by a conserved regulatory module controlling sexual differentiation. In the agricultural pest (Mediterranean fruit fly, or Medfly), we identified a Y-linked gene, (), encoding a small protein that is necessary and sufficient for male development. Silencing or disruption of in XY embryos causes feminization, whereas overexpression of in XX embryos induces masculinization.
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