Long-term outcomes of deep anterior lamellar keratoplasty versus penetrating keratoplasty in Australian keratoconus patients.

PURPOSE: The aim of this study is to compare long-term visual and surgical outcomes after performing deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK) for keratoconus. METHODS: This is a retrospective review of 73 consecutive patients with keratoconus, managed with DALK or PK, between 2000 and 2010, by a single surgeon. Data were collected on baseline parameters, best-corrected visual acuity (BCVA) in logarithm of the mean angle of resolution (logMAR), subjective refraction, graft survival, and complications. RESULTS: Thirty-one (42.5%) eyes underwent a DALK, and 42 (57.5%) eyes underwent a PK. All PK-operated and 29 out of 31 (93.5%) DALK-operated eyes remained clear at the last review. Postoperative complications were significantly more frequent after PK (57.1%) than after DALK (26.5%; P = 0.0197). The mean BCVA was not significantly different for DALK (0.14 logMAR, SD 0.2) versus PK (0.05 logMAR, SD 0.11); however, eyes that underwent PK were more likely to achieve a BCVA of 0.0 logMAR (P = 0.0029). Subjective refraction and method of visual correction (spectacles or contact lenses) were similar for each group. CONCLUSIONS: DALK-operated patients in this study showed similar graft survival, fewer postoperative complications, and equivalent refractive outcomes. No significant difference in the mean BCVA was noted between DALK and PK cases.

UKPMC: a full text article resource for the life sciences.

UK PubMed Central (UKPMC) is a full-text article database that extends the functionality of the original PubMed Central (PMC) repository. The UKPMC project was launched as the first 'mirror' site to PMC, which in analogy to the International Nucleotide Sequence Database Collaboration, aims to provide international preservation of the open and free-access biomedical literature. UKPMC (http://ukpmc.ac.uk) has undergone considerable development since its inception in 2007 and now includes both a UKPMC and PubMed search, as well as access to other records such as Agricola, Patents and recent biomedical theses. UKPMC also differs from PubMed/PMC in that the full text and abstract information can be searched in an integrated manner from one input box. Furthermore, UKPMC contains 'Cited By' information as an alternative way to navigate the literature and has incorporated text-mining approaches to semantically enrich content and integrate it with related database resources. Finally, UKPMC also offers added-value services (UKPMC+) that enable grantees to deposit manuscripts, link papers to grants, publish online portfolios and view citation information on their papers. Here we describe UKPMC and clarify the relationship between PMC and UKPMC, providing historical context and future directions, 10 years on from when PMC was first launched.

A molecular analysis of mutations at the complex dumpy locus in Drosophila melanogaster.

The Drosophila dumpy gene consists of seventy eight coding exons and encodes a huge extracellular matrix protein containing large numbers of epidermal growth factor-like (EGF) modules and a novel module called dumpy (DPY). A molecular analysis of forty five mutations in the dumpy gene of Drosophila melanogaster was carried out. Mutations in this gene affect three phenotypes: wing shape, thoracic cuticular defects, and lethality. Most of the mutations were chemically induced in a single dumpy allele and were analyzed using a nuclease that cleaves single base pair mismatches in reannealed duplexes followed by dHPLC. Additionally, several spontaneous mutations were analyzed. Virtually all of the chemically induced mutations, except for several in a single exon, either generate nonsense codons or lesions that result in downstream stop codons in the reading frame. The remaining chemically induced mutations remove splice sites in the nascent dumpy message. We propose that the vast majority of nonsense mutations that affect all three basic dumpy phenotypes are in constitutive exons, whereas nonsense mutants that remove only one or two of the basic functions are in alternatively spliced exons. Evolutionary comparisons of the dumpy gene from seven Drosophila species show strong conservation of the 5' ends of exons where mutants with partial dumpy function are found. In addition, reverse transcription PCR analyses reveal transcripts in which exons marked by nonsense mutations with partial dumpy function are absent.

dumpy interacts with a large number of genes in the developing wing of Drosophila melanogaster.

The complex Drosophila dumpy gene encodes a gigantic protein located in the apical extracellular matrix of epithelial cells. It has been shown to interact with several proteins notably during embryonic tracheal development. Here we examine Dumpy's interactions in vivo with mutations in 20 genes previously recovered in a screen for recessive lethals that generate blisters when somatic clones are produced by mitotic crossing over during wing development. Primarily using double mutants, we looked for both dominant effects of the wing blister mutants and the effects of blister mutant clones on dumpy expression. Sixteen of the mutants either suppressed or enhanced dumpy mutant phenotypes indicating the large Dumpy protein is a very important component of the epithelial extracellular matrix in the wing. Dumpy also interacts strongly with held out wings, which is involved in RNA localization and possibly alternative splicing.

The rate of unequal crossing over in the dumpy gene from Drosophila melanogaster.

The PIGSFEAST (PF) exon of the Drosophila dumpy gene is undergoing concerted evolution by the process of unequal crossing over. We have developed a long-range PCR-based assay to amplify the approximately 12 kb long exon which contains variable numbers of 303 or 306 nt long repeats in a tandem array. We applied this procedure to mutation accumulation lines of Drosophila melanogaster established by M. Wayne and L. Higgins. Nine new repeat length variants were found in these lines allowing us to measure the rate of unequal crossing over in the PF exon. The rate, which for several reasons is an underestimate, is 7.05 x 10(-4) exchanges per generation.

The alpha glycerophosphate cycle in Drosophila melanogaster V. molecular analysis of alpha glycerophosphate dehydrogenase and alpha glycerophosphate oxidase mutants.

Two enzymes, alpha glycerophosphate dehydrogenase (GPDH-1) in the cytoplasm and alpha glycerophosphate oxidase (GPO-1) in the mitochondrion cooperate in Drosophila flight muscles to generate the ATP needed for muscle contraction. Null mutants for either enzyme cannot fly. Here, we characterize 15 ethyl methane sulfonate (EMS)-induced mutants in GPDH-1 at the molecular level and assess their effects on structural and evolutionarily conserved domains of this enzyme. In addition, we molecularly characterize 3 EMS-induced GPO-1 mutants and excisions of a P element insertion in the GPO-1 gene. The latter represent the best candidate for null or amorphic mutants in this gene.

The alpha glycerophosphate cycle in Drosophila melanogaster VI. structure and evolution of enzyme paralogs in the genus Drosophila.

The genome sequences of 12 Drosophila species contain 3 paralogs for alpha glycerophosphate dehydrogenase (GPDH) and for the mitochondrial alpha glycerophosphate oxidase (GPO). These 2 enzymes participate in the alpha glycerophosphate cycle in the adult thoracic flight muscles. The flight muscle enzymes are encoded by gpdh-1 at 26A2 and gpo-1 at 52C8. In this paper, we show that the GPDH paralogs share the same evolutionarily conserved functional domains and most intron positions, whereas the GPO paralogs share only some of the functional domains of mitochondrial oxidoreductases. The GPO paralogs not expressed in the flight muscles essentially lack introns. GPDH paralogs encoded by gpdh-2 and gpdh-3 and the GPO paralogs encoded by gpo-2 and gpo-3 are expressed only in the testes. Gene trees for the GPDH and GPO paralogs indicate that the genes expressed in the flight muscles are evolving very slowly presumably under strong purifying selection whereas the paralogs expressed in the testes are evolving more rapidly. The concordance between species and gene trees, d(N)/d(S) ratios, phylogenetic analysis by maximum likelihood-based tests, and analyses of radical and conservative substitutions all indicate that the additional GPDH and GPO paralogs are also evolving under purifying selection.

Concerted evolution within the Drosophila dumpy gene.

We have determined by reverse Southern analysis and direct sequence comparisons that most of the dumpy gene has evolved in the dipteran and other insect orders by purifying selection acting on amino acid replacements. One region, however, is evolving rapidly due to unequal crossing over and/or gene conversion. This region, called "PIGSFEAST," or PF, encodes in D. melanogaster 30-47 repeats of 102 amino acids rich in serines, threonines, and prolines. We show that the processes of concerted evolution have been operating on all species of Drosophila examined to date, but that an adjacent region has expanded in Anopheles gambiae, Aedes aegypti, and Tribolium castaneum, while the PF repeats are reduced in size and number. In addition, processes of concerted evolution have radically altered the codon usage patterns in D. melanogaster, D. pseudoobscura, and D. virilis compared with the rest of the dumpy gene. We show also that the dumpy gene is expressed on the inner surface of the micropyle of the mature oocyte and propose that, as in the abalone system, concerted evolution may be involved in adaptive changes affecting Dumpy's possible role in sperm-egg recognition.