Refractive Astigmatism Outcomes of Femtosecond Laser-Assisted Arcuate Keratotomies Combined with Femtosecond Laser-Assisted Cataract Surgery: Two-Year Results.

PURPOSE: To evaluate the effectiveness and stability of refractive astigmatism reduction after penetrating femtosecond laser-assisted arcuate keratotomy performed at the time of femtosecond laser-assisted cataract surgery. METHODS: Non-randomized retrospective data analysis of all patients that underwent femtosecond laser-assisted cataract surgery with femtosecond laser-assisted arcuate keratotomy over a 4-year period with a non-toric monofocal intraocular lens (2017-2021) at a tertiary care academic center. Postoperative visual acuity, manifest refraction, and predicted residual refractive error were also recorded at 1 month, 3-6 months, 12-18 months, and 2 years postoperatively. Preoperative keratometric astigmatism was compared to postoperative refractive astigmatism using vector calculations and the ASCRS double-angle plot tool. RESULTS: This study comprised 266 eyes (179 patients) that met inclusion criteria. The mean preoperative keratometric astigmatism magnitude was 0.99 ± 0.53 D. At 1 month, 3-6 months, 12-18 months, and 2 years postoperatively, the mean refractive cylinder was 0.49 ± 0.45 D, 0.49 ± 0.45 D, 0.55 ± 0.54 D, and 0.52 ± 0.46 D, respectively. Horizontal against-the-rule astigmatism showed a higher tendency toward undercorrection than vertical with-the-rule astigmatism, which had a slightly higher tendency toward overcorrection. With-the-rule astigmatism had smaller difference vectors between target-induced astigmatism and surgically induced astigmatism. CONCLUSIONS: Femtosecond laser-assisted arcuate keratotomy performed at the time of femtosecond laser-assisted cataract surgery was an effective option for correcting low-to-moderate corneal astigmatism for up to 2 years.

Long-read metagenomics of soil communities reveals phylum-specific secondary metabolite dynamics.

Microbial biosynthetic gene clusters (BGCs) encoding secondary metabolites are thought to impact a plethora of biologically mediated environmental processes, yet their discovery and functional characterization in natural microbiomes remains challenging. Here we describe deep long-read sequencing and assembly of metagenomes from biological soil crusts, a group of soil communities that are rich in BGCs. Taking advantage of the unusually long assemblies produced by this approach, we recovered nearly 3,000 BGCs for analysis, including 712 full-length BGCs. Functional exploration through metatranscriptome analysis of a 3-day wetting experiment uncovered phylum-specific BGC expression upon activation from dormancy, elucidating distinct roles and complex phylogenetic and temporal dynamics in wetting processes. For example, a pronounced increase in BGC transcription occurs at night primarily in cyanobacteria, implicating BGCs in nutrient scavenging roles and niche competition. Taken together, our results demonstrate that long-read metagenomic sequencing combined with metatranscriptomic analysis provides a direct view into the functional dynamics of BGCs in environmental processes and suggests a central role of secondary metabolites in maintaining phylogenetically conserved niches within biocrusts.

Bilateral Vision Loss with p-ANCA Associated Lymphocytic Vasculitis.

Purpose: To describe a case of p-ANCA associated vasculitis in a patient with bilateral vision loss with no systemic symptoms or signsMethods: A descriptive review of a caseResults: We report a case of bilateral sequential vision loss in a 73-year-old woman who had no constitutional symptoms except headache and was found to have positive p-ANCA and lymphocytic infiltration on bilateral temporal artery biopsy. Despite the early administration of systemic corticosteroids, the visual outcome was unfavorable.Conclusion: It is important to consider ANCA associated vasculitides when temporal artery biopsy does not support GCA.

Interkingdom Genetic Mix-and-Match To Produce Novel Sunscreens.

Sunscreen-containing skincare products protect the skin from damage caused by sun exposure. However, many of them contain oxybenzone and/or octinoxate, which have been reported to be toxic to juvenile coral and to cause coral bleaching. Thus, there is a growing need for new sunscreen compounds that are less harmful to the environment. Here, we report an engineered biosynthetic pathway employing genes from a vertebrate and two Gram-(+) bacteria that forms novel sunscreen compounds with hybrid structures of gadusol and mycosporine-like amino acids, both of which are found in marine environments. These compounds, named gadusporines, have unique UV absorbance at 340 nm, expanding the range of mycosporine- and gadusol-based sunscreen products. The synthesis of gadusporines in Streptomyces coelicolor establishes a platform for the design and production of novel sunscreens.

The sedoheptulose 7-phosphate cyclases and their emerging roles in biology and ecology.

Covering up to: 1999-2016This highlight covers a family of enzymes of growing importance, the sedoheptulose 7-phosphate cyclases, initially of interest due to their involvement in the biosynthesis of pharmaceutically relevant secondary metabolites. More recently, these enzymes have been found throughout Prokarya and Eukarya, suggesting their broad potential biological roles in nature.

Evolution and Distribution of C7-Cyclitol Synthases in Prokaryotes and Eukaryotes.

2-Epi-5-epi-valiolone synthase (EEVS), a C7-sugar phosphate cyclase (SPC) homologous to 3-dehydroquinate synthase (DHQS), was discovered during studies of the biosynthesis of the C7N-aminocyclitol family of natural products. EEVS was originally thought to be present only in certain actinomycetes, but analyses of genome sequences showed that it is broadly distributed in both prokaryotes and eukaryotes, including vertebrates. Another SPC, desmethyl-4-deoxygadusol synthase (DDGS), was later discovered as being involved in the biosynthesis of mycosporine-like amino acid sunscreen compounds. Current database annotations are quite unreliable, with many EEVSs reported as DHQS, and most DDGSs reported as EEVS, DHQS, or simply hypothetical proteins. Here, we identify sequence features useful for distinguishing these enzymes, report a crystal structure of a representative DDGS showing the high similarity of the EEVS and DDGS enzymes, identify notable active site differences, and demonstrate the importance of two of these active site residues for catalysis by point mutations. Further, we functionally characterized two representatives of a distinct clade equidistant from known EEVS and known DDGS groups and show them to be authentic EEVSs. Moreover, we document and discuss the distribution of genes that encode EEVS and DDGS in various prokaryotes and eukaryotes, including pathogenic bacteria, plant symbionts, nitrogen-fixing bacteria, myxobacteria, cyanobacteria, fungi, stramenopiles, and animals, suggesting their broad potential biological roles in nature.

A Highly Promiscuous ß-Ketoacyl-ACP Synthase (KAS) III-like Protein Is Involved in Pactamycin Biosynthesis.

ß-Ketoacyl-acyl carrier protein (ß-Ketoacyl-ACP) synthase (KAS) III catalyzes the first step in fatty acid biosynthesis, involving a Claisen condensation of the acetyl-CoA starter unit with the first extender unit, malonyl-ACP, to form acetoacetyl-ACP. KAS III-like proteins have also been reported to catalyze acyltransferase reactions using coenzyme A esters or discrete ACP-bound substrates. Here, we report the in vivo and in vitro characterizations of a KAS III-like protein (PtmR), which directly transfers a 6-methylsalicylyl moiety from an iterative type I polyketide synthase to an aminocyclopentitol unit in pactamycin biosynthesis. PtmR is highly promiscuous, recognizing a wide array of S-acyl-N-acetylcysteamines as substrates to produce a suite of pactamycin derivatives with diverse alkyl and aromatic features. The results suggest that KAS III-like proteins may be used as versatile tools for modifications of complex natural products.

Interrogating the Tailoring Steps of Pactamycin Biosynthesis and Accessing New Pactamycin Analogues.

Pactamycin is a bacteria-derived aminocyclitol antibiotic with a wide-range of biological activity. Its chemical structure and potent biological activities have made it an interesting lead compound for drug discovery and development. Despite its unusual chemical structure, many aspects of its formation in nature remain elusive. Using a combination of genetic inactivation and metabolic analysis, we investigated the tailoring processes of pactamycin biosynthesis in Streptomyces pactum. The results provide insights into the sequence of events during the tailoring steps of pactamycin biosynthesis and explain the unusual production of various pactamycin analogues by S. pactum mutants. We also identified two new pactamycin analogues that have better selectivity indexes than pactamycin against malarial parasites.

De novo synthesis of a sunscreen compound in vertebrates.

Ultraviolet-protective compounds, such as mycosporine-like amino acids (MAAs) and related gadusols produced by some bacteria, fungi, algae, and marine invertebrates, are critical for the survival of reef-building corals and other marine organisms exposed to high-solar irradiance. These compounds have also been found in marine fish, where their accumulation is thought to be of dietary or symbiont origin. In this study, we report the unexpected discovery that fish can synthesize gadusol de novo and that the analogous pathways are also present in amphibians, reptiles, and birds. Furthermore, we demonstrate that engineered yeast containing the fish genes can produce and secrete gadusol. The discovery of the gadusol pathway in vertebrates provides a platform for understanding its role in these animals, and the possibility of engineering yeast to efficiently produce a natural sunscreen and antioxidant presents an avenue for its large-scale production for possible use in pharmaceuticals and cosmetics.