Structural Basis for the Peptidoglycan-Editing Activity of YfiH.

Bacterial cells are encased in peptidoglycan (PG), a polymer of disaccharide N-acetylglucosamine (GlcNAc) and N-acetyl-muramic acid (MurNAc) cross-linked by peptide stems. PG is synthesized in the cytoplasm as UDP-MurNAc-peptide precursors, of which the amino acid composition of the peptide is unique, with l-Ala added at the first position in most bacteria but with l-Ser or Gly in some bacteria. YfiH is a PG-editing factor whose absence causes misincorporation of l-Ser instead of l-Ala into peptide stems, but its mechanistic function is unknown. Here, we report the crystal structures of substrate-bound and product-bound YfiH, showing that YfiH is a cytoplasmic amidase that controls the incorporation of the correct amino acid to the nucleotide precursors by preferentially cleaving the nucleotide precursor by-product UDP-MurNAc-l-Ser. This work reveals an editing mechanism in the cytoplasmic steps of peptidoglycan biosynthesis. IMPORTANCE YfiH is a peptidoglycan (PG)-editing factor required for the maintenance of specific amino acid compositions of the stem peptides. However, the activity of YfiH has not been deciphered, and the editing mechanism involving YfiH has remained a mystery. Through X-ray crystallographic and biochemical analyses, we demonstrate that YfiH is a hydrolase with a previously unknown activity specific for the UDP-MurNAc-monopeptide, one of the nucleotide precursors from the cytoplasmic steps of the PG biosynthesis pathway. YfiH selectively hydrolyzes UDP-MurNAc-Ser, an incorrect by-product of the biosynthesis reaction, to ensure that only the correct PG precursor, UDP-MurNAc-Ala, is incorporated. Therefore, this work reveals coupled synthetic and editing reactions in the cytoplasmic steps of PG biosynthesis.

Intraocular lens opacification after Descemet's stripping automated endothelial keratoplasty.

Compared with conventional penetrating keratoplasty, Descemet's stripping automated endothelial keratoplasty (DSAEK) more effectively maintain global integrity and rapid vision rehabilitation with less ocular surface disorders in patients with endothelial dysfunction. Here, we report a case of a 76-year-old woman who experienced opacification of a hydrophilic intraocular lens (IOL) approximately 10 months after DSAEK. The patient with no history of systemic disease developed pseudophakic bullous keratopathy in the right eye 2 years after undergoing cataract surgery. The best-corrected visual acuity (BCVA) of the right eye was Snellen 0.01 when presented to our hospital. DSAEK was arranged and performed smoothly. However, the graft detached over the upper part of the cornea on postoperative day 1. Thus, rebubbling was performed immediately. After the procedure, the graft was well attached, and the cornea became clear gradually. The BCVA returned to Snellen 0.6. However, progressive opacification over the anterior surface of the IOL was observed 10 months postoperatively. Vision deteriorated to 0.5 with various refractive errors during 2-year follow-up. IOL exchange may be considered if the vision is getting worse. IOL opacification may result from a direct contact between the IOL surface and exogenous air, particularly in a hydrophilic IOL, and can be a rare but significant complication after DSAEK. Clinicians planning to perform DSAEK should consider the composition of the IOL, the amount of intracameral air, duration of air filling, and high intraocular pressure.

Is normal-tension glaucoma a risk factor for stroke?-A 10-year follow-up study.

OBJECTIVES: To investigate whether patients with normal-tension glaucoma (NTG) have a higher incidence of stroke. DESIGN: A population-based retrospective cohort study based on data from the Taiwan National Health Insurance Research Database (NHIRD) from January 1, 2001, to December 31, 2010. METHODS: Data were retrospectively collected from the NHIRD. A total of 245 (20.1%) patients with a history of stroke at the time of glaucoma diagnosis were excluded, and 1,218 patients with NTG who were 20 years of age and older were identified. Patients' age, gender and pre-existing comorbidities, including hypertension, diabetes, congestive heart failure, ischemic heart disease, atrial fibrillation and disorders of lipid metabolism, were recorded. The propensity score method with a 1:5 matching ratio was used to minimize selection bias. Cox regression with robust variance estimation was used to estimate the hazard ratio (HR) of developing stroke between the NTG and control groups. RESULTS: After adjusting for patient age, gender, and pre-existing comorbidities, the HR was 6.34, indicating that the incidence of stroke was significantly higher in patients with NTG than in controls. Furthermore, a higher risk of stroke was also found in most subgroups with the above-mentioned comorbidities. CONCLUSION: NTG is a significant risk factor for subsequent stroke in most of the described comorbidity subgroups. Early interventions for stroke prevention should be provided to newly diagnosed patients with NTG.