Visual Impairment as a Function of Visual Acuity in Both Eyes and Its Impact on Patient Reported Preferences

Purpose

To assess the impact of VA loss on patient reported utilities taking both eyes into account compared to taking only the better or the worse eye into account.

Methods

In this cross-sectional study 1085 patients and 254 controls rated preferences with the generic health-related (EQ-5D; n = 868) and vision-specific (Vision and Quality of Life Index (VisQoL); n = 837) multi-attribute utility instruments (MAUIs). Utilities were calculated for three levels of VA in the better and worse eyes, as well as for 6 different vision states based on combinations of the better and worse eye VA.

Results

Using the VisQoL, utility scores decreased significantly with deteriorating vision in both the better and worse eyes when analysed separately. When stratified by the 6 vision states, VisQoL utilities decreased as VA declined in the worse eye despite stable VA in the better eye. Differences in VisQoL scores were statistically significant for cases where the better eye had no vision impairment and the worse seeing fellow eye had mild, moderate or severe vision impairment. In contrast, the EQ-5D failed to capture changes in better or worse eye VA, or any of the six vision states.

Conclusions

Calculating utilities based only on better eye VA or using a generic MAUI is likely to underestimate the impact of vision impairment, particularly when the better eye has no or little VA loss and the worse eye is moderately to severely visually impaired. These findings have considerable implications for the assessment of overall visual impairment as well as economic evaluations within eye health.     

Augmenting Endogenous Wnt Signaling Improves Skin Wound Healing

Wnt signaling is required for both the development and homeostasis of the skin, yet its contribution to skin wound repair remains controversial. By employing Axin2^LacZ/+ reporter mice we evaluated the spatial and temporal distribution patterns of Wnt responsive cells, and found that the pattern of Wnt responsiveness varies with the hair cycle, and correlates with wound healing potential. Using Axin2^LacZ/LacZ mice and an ear wound model, we demonstrate that amplified Wnt signaling leads to improved healing. Utilizing a biochemical approach that mimics the amplified Wnt response of Axin2^LacZ/LacZ mice, we show that topical application of liposomal Wnt3a to a non-healing wound enhances endogenous Wnt signaling, and results in better skin wound healing. Given the importance of Wnt signaling in the maintenance and repair of skin, liposomal Wnt3a may have widespread application in clinical practice.     

Variable δ15N Diet-Tissue Discrimination Factors among Sharks: Implications for Trophic Position,Diet and Food Web Models

The application of stable isotopes to characterize the complexities of a species foraging behavior and trophic relationships is dependent on assumptions of δ¹⁵N diet-tissue discrimination factors (∆¹⁵N). As ∆¹⁵N values have been experimentally shown to vary amongst consumers, tissues and diet composition, resolving appropriate species-specific ∆¹⁵N values can be complex. Given the logistical and ethical challenges of controlled feeding experiments for determining ∆¹⁵N values for large and/or endangered species, our objective was to conduct an assessment of a range of reported ∆¹⁵N values that can hypothetically serve as surrogates for describing the predator-prey relationships of four shark species that feed on prey from different trophic levels (i.e., different mean δ¹⁵N dietary values). Overall, the most suitable species-specific ∆¹⁵N values decreased with increasing dietary-δ¹⁵N values based on stable isotope Bayesian ellipse overlap estimates of shark and the principal prey functional groups contributing to the diet determined from stomach content analyses. Thus, a single ∆¹⁵N value was not supported for this speciose group of marine predatory fishes. For example, the ∆¹⁵N value of 3.7‰ provided the highest percent overlap between prey and predator isotope ellipses for the bonnethead shark (mean diet δ¹⁵N = 9‰) whereas a ∆¹⁵N value < 2.3‰ provided the highest percent overlap between prey and predator isotope ellipses for the white shark (mean diet δ¹⁵N = 15‰). These data corroborate the previously reported inverse ∆¹⁵N-dietary δ¹⁵N relationship when both isotope ellipses of principal prey functional groups and the broader identified diet of each species were considered supporting the adoption of different ∆¹⁵N values that reflect the predators’ δ¹⁵N-dietary value. These findings are critical for refining the application of stable isotope modeling approaches as inferences regarding a species’ ecological role in their community will be influenced with consequences for conservation and management actions.     

Avoidance and aggregation create consistent egg distribution patterns of congeneric caddisflies across spatially variable oviposition landscapes

Oecologia - Amongst oviparous animals, the spatial distribution of individuals is often set initially by where females lay eggs, with potential implications for populations and species coexistence....     

Arabinose-rich polymers as an evolutionary strategy to plasticize resurrection plant cell walls against desiccation

A variety of Southern African resurrection plants were surveyed using high-throughput cell wall profiling tools. Species evaluated were the dicotyledons, Myrothamnus flabellifolia and Craterostigma plantagineum; the monocotyledons, Xerophyta viscosa, Xerophyta schlecterii, Xerophyta humilis and the resurrection grass Eragrostis nindensis, as well as a pteridophyte, the resurrection fern, Mohria caffrorum. Comparisons were made between hydrated and desiccated leaf and frond material, with respect to cell wall composition and polymer abundance, using monosaccharide composition analysis, FT-IR spectroscopy and comprehensive microarray polymer profiling in combination with multivariate data analysis. The data obtained suggest that three main functional strategies appear to have evolved to prepare plant cell walls for desiccation. Arabinan-rich pectin and arabinogalactan proteins are found in the resurrection fern M. caffrorum and the basal angiosperm M. flabellifolia where they appear to act as ‘pectic plasticizers’. Dicotyledons with pectin-rich walls, such as C. plantagineum, seem to use inducible mechanisms which consist of up-regulating wall proteins and osmoprotectants. The hemicellulose-rich walls of the grass-like Xerophyta spp. and the resurrection grass E. nindensis were found to contain highly arabinosylated xylans and arabinogalactan proteins. These data support a general mechanism of ‘plasticising’ the cell walls of resurrection plants to desiccation and implicate arabinose-rich polymers (pectin-arabinans, arabinogalactan proteins and arabinoxylans) as the major contributors in ensuring flexibility is maintained and rehydration is facilitated in these plants.     

Detection of Biosignatures by Geomatrix-Assisted Laser Desorption/Ionization (GALDI) Mass Spectrometry

Identification of mineral-associated biosignatures is of significance for retrieving biochemical information from geological records here on Earth and for detecting signs of life on other planets, such as Mars. An investigation using laser desorption Fourier transform mass spectrometry was conducted to determine whether geomatrix-assisted laser desorption/ionization (GALDI) can be used to detect amino acids (e.g., histidine, threonine, and cysteine) and small proteins (e.g., gramicidin S) associated with mineral phases and whether the geomatrix impacts detection. Iron oxide (Fe₂ O ₃ ) and sodium chloride (NaCl) were investigated as clean chemical analogues of hematite and halite, respectively, which have both been detected on the surface of Mars. Samples were prepared by 2 methods: (1) application of analyte solution to the geomatrix surface with subsequent drying; and (2) physical mixing of analyte and geomatrix. Amino acids incorporated within NaCl by physical mixing yielded a better signal-to-noise ratio than those that were applied to the surface of a NaCl pellet. The composition of the geomatrix had an influence on the detection of biomolecules. Peaks corresponding to the cation-attached biomolecular ions were observed for the NaCl prepared samples. However, no biomolecular ion species were observed in samples using Fe ₂ O ₃ as geomatrix. Instead, only minor peaks that may correspond to ions derived from fragments of the biomolecules were obtained.     

The tumor suppressor CDKN3 controls mitosis

Mitosis is controlled by a network of kinases and phosphatases. We screened a library of small interfering RNAs against a genome-wide set of phosphatases to comprehensively evaluate the role of human phosphatases in mitosis. We found four candidate spindle checkpoint phosphatases, including the tumor suppressor CDKN3. We show that CDKN3 is essential for normal mitosis and G1/S transition. We demonstrate that subcellular localization of CDKN3 changes throughout the cell cycle. We show that CDKN3 dephosphorylates threonine-161 of CDC2 during mitotic exit and we visualize CDC2^pThr-161 at kinetochores and centrosomes in early mitosis. We performed a phosphokinome-wide mass spectrometry screen to find effectors of the CDKN3-CDC2 signaling axis. We found that one of the identified downstream phosphotargets, CKβ phosphorylated at serine 209, localizes to mitotic centrosomes and controls the spindle checkpoint. Finally, we show that CDKN3 protein is down-regulated in brain tumors. Our findings indicate that CDKN3 controls mitosis through the CDC2 signaling axis. These results have implications for targeted anticancer therapeutics.