Hijacking of N-fixing legume albumin-1 genes enables the cyclization and stabilization of defense peptides.

The legume albumin-1 gene family, arising after nodulation, encodes linear a- and b-chain peptides for nutrient storage and defense. Intriguingly, in one prominent legume, Clitoria ternatea, the b-chains are replaced by domains producing ultra-stable cyclic peptides called cyclotides. The mechanism of this gene hijacking is until now unknown. Cyclotides require recruitment of ligase-type asparaginyl endopeptidases (AEPs) for maturation (cyclization), necessitating co-evolution of two gene families. Here we compare a chromosome-level C. ternatea genome with grain legumes to reveal an 8 to 40-fold expansion of the albumin-1 gene family, enabling the additional loci to undergo diversification. Iterative rounds of albumin-1 duplication and diversification create four albumin-1 enriched genomic islands encoding cyclotides, where they are physically grouped by similar pI and net charge values. We identify an ancestral hydrolytic AEP that exhibits neofunctionalization and multiple duplication events to yield two ligase-type AEPs. We propose cyclotides arise by convergence in C. ternatea where their presence enhances defense from biotic attack, thus increasing fitness compared to lineages with linear b-chains and ultimately driving the replacement of b-chains with cyclotides.

Prospective study on a novel treatment for leaking cystic bleb: Efficacy and safety of collagen crosslinking.

IMPORTANCE: Management of cystic bleb leak is difficult. It would be essential to look for a method to strengthen the original pathological conjunctiva and reverse bleb leak. BACKGROUND: To evaluate the long-term efficacy and safety of collagen crosslinking in patients with leaking cystic bleb. DESIGN: Prospective interventional case series at a university-based hospital. PARTICIPANTS: Twelve eyes in 12 subjects with late-onset bleb leak from cystic bleb, without indications for prompt surgical interventions were included. METHODS: The subjects underwent crosslinking with 0.1% riboflavin application to bleb surface, followed by ultraviolet irradiation for 30 minutes. The subjects were followed up at baseline and at 1 week, 1 month, 3 months, 6 months post-treatment and then every 6 months afterwards. MAIN OUTCOME MEASURES: Interval from treatment to cessation of bleb leak, recurrence rate of bleb leak and side effects of treatment. RESULTS: The mean follow-up after crosslinking was 29.33 ± 12.45 months. Bleb leak subsided in 11 (92%) of 12 patients after a single session of crosslinking, after 1 to 8 weeks (median 3 weeks). Time to leak cessation was significantly correlated with the number of prior glaucoma interventions (R = .71, P = .014). Bleb wall at 3 months was significantly thicker than at baseline (0.70 ± 0.67 vs 0.81 ± 0.62 mm, P = .008). None of the patients experienced any complications. CONCLUSIONS AND RELEVANCE: Crosslinking achieves resolution of cystic bleb leak which lasts for at least 12 months, without the need of subsequent surgical interventions. Crosslinking is a simple, non-invasive treatment for bleb leak. It aims to restore the integrity of conjunctiva.

The ophthalmological complications of targeted agents in cancer therapy: what do we need to know as ophthalmologists?

Recently, there has been an increase in the use of targeted therapies for cancer treatments. Nevertheless, the ocular side-effects of the commonly used targeted agents are generally under-reported and not well studied in the literature. We conducted multiple searches in databases, including Medline, EMBASE, Cochrane Library and conference proceedings, using the following strings: 'name of targeted therapeutic agent (both generic and commercial names)' AND 'eye OR ocular OR vision OR ophthalmological'. Various targeted agents have been found to be associated with ocular side-effects due to their specific targeting of activities in the eye. Imatinib commonly causes periorbital oedema, epiphora and occasionally conjunctival haemorrhage. Cetuximab causes corneal lesions, meibomian gland dysfunction, periorbital and lid dermatitis, blepharitis and conjunctivitis. Erlotinib is related to various ocular toxicities, mainly on the ocular surface, and perifosine has been reported to be associated with severe keratitis. Bevacizumab could potentially disrupt intrinsic ocular circulation and lead to the development of thromboembolic events; there are rare reported cases of optic neuritis or optic neuropathy. Other targeted agents, such as trastuzumab, sunitinib and crizotinib, also have specific ocular toxicities. In conclusion, ocular effects of targeted agents are not uncommon in cancer patients receiving targeted therapy. Ophthalmologists should have high indexes of suspicion to diagnose and treat these complications promptly.