To present initial clinical experience with small-incision lenticule extraction for the treatment of moderate to high myopia.
Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark.
...Prospective clinical study.
For small-incision lenticule extraction, an intrastromal lenticule was cut with a femtosecond laser and manually extracted without creation of a flap. Patients were treated and followed for 3 months. Only 1 randomly chosen eye of each patient was used in the statistical analyses.
The study enrolled 144 patients. The mean preoperative spherical equivalent was -7.18 diopters (D) ± 1.57 (SD). Of eyes with emmetropia as target refraction, 40% had an uncorrected distance visual acuity of 0.1 logMAR or less 1 day after surgery; this increased to 73% at 3 months. The mean corrected distance visual acuity (CDVA) improved significantly from -0.01 (logMAR) preoperatively to -0.03 3 months postoperatively. None of the 127 eyes lost 2 lines or more of CDVA and 6 eyes lost 1 line of CDVA after 3 months. In contrast, 1 eye gained 2 lines and 24 eyes gained 1 line of CDVA. The achieved refraction was a mean of -0.09 ± 0.45 D from the attempted refraction. Of the eyes, 77% were within ±0.50 D and 95% were within ±1.00 D. Ninety-five percent of the patients would recommend the procedure to others.
The refractive predictability, safety, and patient satisfaction 3 months after small-incision lenticule extraction were high and comparable to results in previous studies of femtosecond laser-assisted techniques.
Drs. Hjortdal and Asp received travel reimbursement from Carl Zeiss Meditec AG, Jena, Germany. No other author has a financial or proprietary interest in any material or method mentioned.
To compare femtosecond lenticule extraction and small-incision lenticule extraction to treat moderate to high myopia.
Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark.
...Prospective clinical single-masked paired-eye study.
An intrastromal lenticule was cut by a femtosecond laser and manually extracted. In femtosecond lenticule extraction, a laser in situ keratomileusis-like flap allowed removal of the lenticule, whereas in small-incision lenticule extraction, it was removed through a small incision. Follow-up was 6 months.
Thirty-five patients were treated with femtosecond lenticule extraction in 1 eye and small-incision lenticule extraction in the other. The mean preoperative spherical equivalent was -7.6 diopters (D) ± 1.0 (SD) (range -6.0 to -9.9 D). After both procedures, 90% of eyes had an uncorrected distance visual acuity of 20/40 or better 1 day postoperatively, increasing to 100% after 6 months. At 6 months, the mean corrected distance visual acuity (CDVA) improved significantly by approximately 1.5 letters on the logMAR chart. No eyes lost or gained 2 lines or more of CDVA after either procedure. The achieved refraction was a mean of -0.04 ± 0.38 D from the attempted refraction after femtosecond lenticule extraction and -0.09 ± 0.39 D after small-incision lenticule extraction. After both procedures, 88% of eyes were within ±0.50 D. Contrast sensitivity was unchanged. The changes in higher-order aberrations were similar.
The all-femtosecond laser flap-based and cap-based techniques produced almost identical results up to 6 months postoperatively in eyes with moderate to high myopia.
Interactomes are often measured using affinity purification-mass spectrometry (AP-MS) or yeast two-hybrid approaches, but these methods do not provide stoichiometric or temporal information. We ...combine quantitative proteomics and size-exclusion chromatography to map 291 coeluting complexes. This method allows mapping of an interactome to the same depth and accuracy as AP-MS with less work and without overexpression or tagging. The use of triplex labeling enables monitoring of interactome rearrangements.
Sequencing of whole cancer genomes has revealed an abundance of recurrent mutations in gene-regulatory promoter regions, in particular in melanoma where strong mutation hotspots are observed adjacent ...to ETS-family transcription factor (TF) binding sites. While sometimes interpreted as functional driver events, these mutations are commonly believed to be due to locally inhibited DNA repair. Here, we first show that low-dose UV light induces mutations preferably at a known ETS promoter hotspot in cultured cells even in the absence of global or transcription-coupled nucleotide excision repair (NER). Further, by genome-wide mapping of cyclobutane pyrimidine dimers (CPDs) shortly after UV exposure and thus before DNA repair, we find that ETS-related mutation hotspots exhibit strong increases in CPD formation efficacy in a manner consistent with tumor mutation data at the single-base level. Analysis of a large whole genome cohort illustrates the widespread contribution of this effect to recurrent mutations in melanoma. While inhibited NER underlies a general increase in somatic mutation burden in regulatory elements including ETS sites, our data supports that elevated DNA damage formation at specific genomic bases is at the core of the prominent promoter mutation hotspots seen in skin cancers, thus explaining a key phenomenon in whole-genome cancer analyses.
Abstract
The bacterial and archaeal community structure was examined in two methanogenic anaerobic digestion processes degrading organic household waste at mesophilic (37°C) and thermophilic (55°C) ...temperatures. Analysis of bacterial clone libraries revealed a predominance of Bacteroidetes (34% of total clones) and Chloroflexi (27%) at the mesophilic temperature. In contrast, in the thermophilic clone library, the major group of clones were affiliated with Thermotogae (61%). Within the domain Archaea, the phyla Euryarchaeota and Crenarchaeota were both represented, the latter only at the mesophilic temperature. The dominating archaeons grouped with Methanospirillum and Methanosarcina species at the mesophilic and thermophilic temperature, respectively. Generally, there was a higher frequency of different sequences at the lower temperature, suggesting a higher diversity compared to the community present at the thermophilic temperature. Furthermore, it was not only the species richness that was affected by temperature, but also the phylogenetic distribution of the microbial populations.
Recent research has illustrated that demographic diversity influences the outcomes of public sector organizations. Most studies have focused on workforce diversity; by comparison, little is known ...about how managerial diversity affects organizational outcomes. This article focuses on gender diversity in the top management teams of public organizations and its relationship to financial performance. Theory suggests that management diversity can be a positive asset for organizations, allowing for the use of more diverse knowledge and human skill sets. Results of this study, however, suggest that organizations may only be able to leverage these advantages if they have a supporting management structure. In a longitudinal study of top management teams in Danish municipalities, the authors find that gender diversity in top management teams is associated with higher financial performance, but only in municipalities with a management structure that supports cross-functional team work. These results are interpreted in light of existing theory, and implications are suggested.
PMEL is an amyloidogenic protein that appears to be exclusively expressed in pigment cells and forms intralumenal fibrils within early stage melanosomes upon which eumelanins deposit in later stages. ...PMEL is well conserved among vertebrates, and allelic variants in several species are associated with reduced levels of eumelanin in epidermal tissues. However, in most of these cases it is not clear whether the allelic variants reflect gain-of-function or loss-of-function, and no complete PMEL loss-of-function has been reported in a mammal. Here, we have created a mouse line in which the Pmel gene has been inactivated (Pmel⁻/⁻). These mice are fully viable, fertile, and display no obvious developmental defects. Melanosomes within Pmel⁻/⁻ melanocytes are spherical in contrast to the oblong shape present in wild-type animals. This feature was documented in primary cultures of skin-derived melanocytes as well as in retinal pigment epithelium cells and in uveal melanocytes. Inactivation of Pmel has only a mild effect on the coat color phenotype in four different genetic backgrounds, with the clearest effect in mice also carrying the brown/Tyrp1 mutation. This phenotype, which is similar to that observed with the spontaneous silver mutation in mice, strongly suggests that other previously described alleles in vertebrates with more striking effects on pigmentation are dominant-negative mutations. Despite a mild effect on visible pigmentation, inactivation of Pmel led to a substantial reduction in eumelanin content in hair, which demonstrates that PMEL has a critical role for maintaining efficient epidermal pigmentation.
Azaphilones are a class of fungal pigments, reported mostly in association with
Monascus
species. In Asian countries, they are used as food colourants under the name of “red yeast rice” and their ...production process is well described. One major limitation of current production techniques of azaphilones is that they always occur in a mixture of yellow, orange and red pigments. These mixtures are difficult to control and to quantify. This study has established a controlled and reproducible cultivation protocol to selectively tailor production of individual pigments during a submerged fermentation using another fungal species capable of producing azaphilone pigments,
Talaromyces atroroseus
, using single amino acids as the sole nitrogen source. The produced azaphilone pigments are called atrorosins and are amino acid derivatives of the known azaphilone pigment
Penicillium purpurogenum–
orange (PP-O), with the amino acid used as nitrogen source incorporated into the core skeleton of the azaphilone. This strategy was successfully demonstrated using 18 proteinogenic amino acids and the non-proteinogenic amino acid ornithine. Two cultivation methods for production of the pure serine derivative (atrorosin S) have been further developed, with yields of 0.9 g/L being obtained. Yielding pure atrorosins through switching from KNO
3
to single amino acids as nitrogen source allows for considerably easier downstream processing and thus further enhances the commercial relevance of azaphilone producing fungal cell factories.
External perturbations, by forcing cells to adapt to a new environment, often elicit large‐scale changes in gene expression resulting in an altered proteome that improves the cell's fitness in the ...new conditions. Steady‐state levels of a proteome depend on transcription, the levels of transcripts, translation and protein degradation but system‐level contribution that each of these processes make to the final protein expression change has yet to be explored. We therefore applied a systems biology approach to characterize the regulation of protein expression during cellular differentiation using quantitative proteomics. As a general rule, it seems that protein expression during cellular differentiation is largely controlled by changes in the relative synthesis rate, whereas the relative degradation rate of the majority of proteins stays constant. In these data, we also observe that the proteins in defined sub‐structures of larger protein complexes tend to have highly correlated synthesis and degradation rates but that this does not necessarily extend to the holo‐complex. Finally, we provide strong evidence that the generally poor correlation observed between transcript and protein levels can fully be explained once the protein synthesis and degradation rates are taken into account.
The contribution of transcription, protein synthesis and degradation rates to the control of protein expression during differentiation was analyzed using quantitative proteomics and transcriptomics data. Protein synthesis rate was identified as the main determinant of protein expression.
Synopsis
The contribution of transcription, protein synthesis and degradation rates to the control of protein expression during differentiation was analyzed using quantitative proteomics and transcriptomics data. Protein synthesis rate was identified as the main determinant of protein expression.
The lack of correlation usually observed between transcript and protein levels can be fully explained when correcting for the synthesis and degradation rates of the individual proteins.
Synthesis rates for individual proteins are extensively regulated, in contrast to degradation rates that mostly remain constant in response to differentiation.
The modularity of macromolecular complexes is maintained during synthesis and degradation of the complexes.
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