The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5′ ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.

The ability to non-invasively predict outcomes and monitor treatment response in primary central nervous system lymphoma (PCNSL) is important as treatment regimens are constantly being trialed. The aim of this study was to assess the validity of using apparent diffusion coefficient (ADC) histogram values to predict Ki-67 expression, a tumor proliferation marker, and patient outcomes in PCNSL in both immunocompetent patients and patients living with HIV (PLWH). Qualitative PCNSL magnetic resonance imaging (MRI) characteristics from 93 patients (23 PLWH and 70 immunocompetent) were analyzed, and whole tumor segmentation was performed on the ADC maps. Quantitative histogram analyses of the segmentations were calculated. These measures were compared to PCNSL Ki-67 expression. Progression-free survival (PFS) and overall survival (OS) were analyzed via comparison to the International Primary Central Nervous System Lymphoma Collaboration Group Response Criteria. Associations between ADC measures and clinical outcomes were assessed using univariate and multivariate Cox proportional hazards models. Normalized ADC (nADC)_Min, nADC_Mean, nADC₁, nADC₅, and nADC₁₅ values were significantly associated with a poorer OS. nADC_Max, nADC_Mean, nADC₅, nADC₁₅, nADC₇₅, nADC₉₅, nADC₉₉ inversely correlated with Ki-67 expression. OS was also significantly associated with lesion hemorrhage. PFS was not significantly associated with ADC values but with lesion hemorrhage. ADC histogram values and related parameters can predict the degree of tumor proliferation and patient outcomes for primary central nervous system lymphoma patients and in both immunocompetent patients and patients living with HIV.

α-Halo thioesters undergo soft enolization and syn-selective direct aldol addition to aldehydes in the presence of MgBr₂·OEt₂ and i-Pr₂NEt to produce α-halo-β-hydroxy thioesters.