Expression of procollagen C proteinase enhancer proteins in human trabecular meshwork cells and tissues

Primary open angle glaucoma (POAG) is the most common form of glaucoma. Ocular hypertension is a major risk factor for POAG and is caused by increased aqueous humor (AH) outflow resistance in the trabecular meshwork (TM). Increased extracellular matrix (ECM) deposition within the TM is correlated with ocular hypertension. Transforming Growth Factor beta 2 (TGFβ2) levels are elevated in the AH and TM of POAG patients, and TGFβ2 increases ECM protein expression, aqueous outflow resistance, and intraocular pressure (IOP). Recently, TGFβ2 was found to induce bone morphogenetic protein 1 (BMP1) expression in TM cells suggesting that BMP1 activity might be involved in glaucoma pathogenesis. Procollagen C proteinase enhancers (PCOLCE 1 and PCOLCE 2) regulate BMP1 activity. Therefore, PCOLCE1 and PCOLCE2 may play an important role(s) in regulating ECM structural changes in the TM, and contribute to AH outflow resistance and elevated IOP in glaucoma. The purpose of this study was to determine if human TM cells and tissues express PCOLCE1 and PCOLCE2 and whether TGFβ2 induces their expression. This is the first documentation that PCOLCE1 and PCOLCE2 are expressed in TM cells and tissues and that TGFβ2 does induce expression of PCOLCE1

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

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