Inhibition of UVR‐Induced Tanning and Immunosuppression by Topical Applications of Vitamins C and E to the Skin of Hairless (hr/hr) Mice 1

Exposure of C3HBYB/Wq hairless (hr/hr) mice to ultra‐violet radiation (UVR) for 15 days induced intense tanning of their dorsal skin. Small, dark freckles appeared first, gradually enlarging and coalescing as treatment progressed yielding a uniform tan. Histologically, the gross changes in skin color were matched initially by the appearance of scattered epidermal melanocytes that subsequently proliferated to form discrete, progressively expanding and abutting populations resulting in a uniform melanocyte network throughout the basal layer of the interfollicular epidermis. In contrast, when applied topically before each daily exposure to UVR, a cream or lotion vehicle containing both vitamins C and E (Vits C/E) inhibited UVR‐induced erythema and tanning. Application of Vits C/E, both before and after irradiation, was no more effective in providing photoprotection than pre‐treatment only. At the tissue level, UVR‐induced proliferation and melanogenesis of melanocytes were reduced compared with irradiated controls. The density of individual melanocyte populations was reduced, as was the number of melanocyte populations achieving merger (confluence) with others. Confluence grades and cell counts, estimating the maximum density of melanocyte populations in UVR–Vits C/E‐treated mice, were approximately two thirds those of UVR–vehicle‐treated controls. However, tanning was only one fifth that of UVR–vehicle‐treated controls, suggesting that melanogenesis was also inhibited. In addition to its inhibitory actions on irradiated melanocytes, Vits C/E also inhibited UVR‐induced suppression of contact hypersensitivity (CHS) in haired (Hr/hr) and hr/hr mice of the C3HBYB/Wq strain. The common denominators for most, if not all, of the influences of topically‐applied Vits C/E in muting the responses of the melanocyte and immune systems to UVR may stem from the vitamins’ combined ability to suppress UVR‐stimulated inflammation and its associated cascade of mediators.     

Glomalean mycorrhizal fungi from tropical Australia

 The isolation of vesicular-arbuscular mycorrhizal (VAM) fungi from natural (savanna, rocky hill, wetland and rainforest) and disturbed (minesite) habitats in a seasonally-dry tropical region in the Northern Territory of Australia into open-pot cultures was undertaken to supplement knowledge about the diversity of these fungi. This experiment considered factors affecting the diversity of fungi obtained in trap cultures started using diluted soil from field sites and two host plants. A range of soil phosphorus and other nutrient levels from severely deficient to sufficient for maximal growth was used to determine the impact of nutrition on mycorrhizal associations of sorghum (Sorghum sp.) and clover (Trifolium subterraneum). Soil cores taken from pots at 6-week intervals provided roots and soil to assess mycorrhiza formation and sporulation without substantial damage to plants. The identification of VAM fungi to genus by observing morphological patterns within clover roots revealed substantial differences in fungus populations between soils and a moderate effect of nutrient levels on fungal diversity. Changes in the proportion of different fungi in roots over the 31 weeks of the experiment were also observed. Glomus spp. were initially the most abundant fungi within roots, but Scutellospora spp. gradually became more dominant at later harvests, while colonisation by Acaulospora spp. was limited at all times. For both clover and sorghum, sporulation was limited and was dominated by single species of Scutellospora and Acaulospora. This contrasted with the much higher diversity of spore types in the original field soils.     

Enhancement of HERG K(+) currents by Cd(2+) destabilization of the inactivated state

We have studied the functional effects of extracellular Cd(2+) on human ether-a-go-go-related gene (HERG) encoded K(+) channels. Low concentrations (10-200 &mgr;M) of extracellular Cd(2+) increased outward currents through HERG channels; 200 &mgr;M Cd(2+) more than doubled HERG currents and altered current kinetics. Cd(2+) concentrations up to 200 &mgr;M did not change the voltage dependence of channel activation, but shifted the voltage dependence of inactivation to more depolarized membrane potentials. Cd(2+) concentrations >/=500 &mgr;M shifted the voltage dependence of channel activation to more positive potentials. These results are consistent with a somewhat specific ability of Cd(2+) to destabilize the inactivated state. We tested the hypothesis that channel inactivation is essential for Cd(2+)-induced increases in HERG K(+) currents, using a double point mutation (G628C/S631C) that diminishes HERG inactivation (Smith, P. L., T. Baukrowitz, and G. Yellen. 1996. Nature (Lond.). 379:833-836). This inactivation-removed mutant is insensitive to low concentrations of Cd(2+). Thus, Cd(2+) had two distinct effects on HERG K(+) channels. Low concentrations of Cd(2+) caused relatively selective effects on inactivation, resulting in a reduction of the apparent rectification of the channel and thereby increasing HERG K(+) currents. Higher Cd(2+) concentrations affected activation gating as well, possibly by a surface charge screening mechanism or by association with a lower affinity site.     

Chemically induced senescence in human stem cell‐derived neurons promotes phenotypic presentation of neurodegeneration

Modeling age‐related neurodegenerative disorders with human stem cells are difficult due to the embryonic nature of stem cell‐derived neurons. We developed a chemical cocktail to induce senescence of iPSC‐derived neurons to address this challenge. We first screened small molecules that induce embryonic fibroblasts to exhibit features characteristic of aged fibroblasts. We then optimized a cocktail of small molecules that induced senescence in fibroblasts and cortical neurons without causing DNA damage. The utility of the “senescence cocktail” was validated in motor neurons derived from ALS patient iPSCs which exhibited protein aggregation and axonal degeneration substantially earlier than those without cocktail treatment. Our “senescence cocktail” will likely enhance the manifestation of disease‐related phenotypes in neurons derived from iPSCs, enabling the generation of reliable drug discovery platforms.     

A comparison of the phytosociology and dynamics of three floodplain (Várzea) forests of known ages, Rio Jurua, western Brazilian Amazon

CAMPBELL, D. G., STONE, J. L. & ROSAS Jr, A., 1992. A comparison of the phytosociology and dynamics of three floodplain (Várzea) forests of known ages, Rio Juruá, western Brazilian Amazon. An unusual historic accident has resulted in three adjacent inundated (vórzea) forests of known ages (50 years old, 14–50 years old, and 14 years old), on the margin of the Rio Juruá, near the village of Rodrigues Alves in western Acre, Brazilian Amazon. One-hectare quantitative inventories (500 × 20 m) were conducted on each of the three forests. Physical characteristics of the plots, including soil particle size, soil cation levels, level of inundation and rate of soil deposition were measured. Plot 1, steeply sloping and ecotonal between várzea and terra firme, was infrequently flooded, with a mean high water mark of 0.0. Plot 2, on slightly undulating terrain, had a mean high water mark of 1.16 m. Plot 3 was level and deeply-flooded, with a mean high water mark of 4.00 m. All trees ≥ 10 cm diameter at breast height (dbh) were mapped, measured and identified to species. Plots 1, 2 and 3 contained 523, 420 and 777 trees, 106, 73 and 20 species, Shannon diversity indices of 3.60, 3.51 and 1.82, and stand basal areas of 25.46 m², 27.01 m² and 25.72 m², respectively. Alchomea triplinervia was the superior competitor on species-rich plot 1; Annona sp. strongly dominated in the limiting conditions of plot 3. On plot 2, no single species was able to achieve dominance. For the 25 species with N≥ 10, habitat specialization as a function of the level of annual inundation was demonstrated, and for five of these species that occurred on plot 1, further refinement of niche as a function of gradient was demonstrated. One-year mortality in plots 1, 2 and 3, was 1.99%, 1.56% and 1.70%, respectively. In Plot 3, 77% of the mortalities were trees that had died standing, vs 40% and 43% in plots 1 and 2.