Enhancing 1α-Hydroxylase Activity with the 25-Hydroxyvitamin D-1α-Hydroxylase Gene in Cultured Human Keratinocytes and Mouse Skin

1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) and its analogs are used to treat psoriasis because of their potent antiproliferative activity. They have the potential for causing hypercalcemia, however, and patients often become resistant to the drug. We examined the feasibility of enhancing the cutaneous production of 1α,25(OH)2D3 using a human 25-hydroxyvitamin D-1α-hydroxylase (1α-OHase) plasmid. The 1α-OHase gene was fused to the green fluorescent protein gene (1α-OHase-GFP) driven by the cytomegalovirus promoter. Transfection of cultured normal human keratinocytes with the 1α-OHase-GFP plasmid resulted in a marked increase in the expression of 1α-OHase-GFP in the mitochondria. Transfection of keratinocytes with 1α-OHase-GFP or 1α-OHase plasmids in vitro enhanced the 1α-OHase activity substantially and increased the sensitivity of the keratinocytes to the antiproliferative effect of 25(OH)D3. The 1α-OHase-GFP plasmid was topically applied to shaved C57/BL6 mice. Twenty-four hours after topical application, immunohistochemical analysis of the skin for 1α-OHase-GFP revealed the presence of 1α-OHase-GFP in the epidermis and epidermal appendages including the hair follicles. The results from this study offer a unique new approach for the topical treatment of hyperproliferative disorders such as psoriasis and skin cancer using the 1α-OHase gene that could locally increase the production of 1α,25(OH)2D3 without causing hypercalcemia or resistance

The effects of infaunal biodiversity on biogeochemistry of coastal marine sediments

We tested the role of benthic infaunal functional diversity in regulating the biogeochemistry of nearshore sediments using laboratory microcosms. Single and multispecies assemblages of deposit-feeding polychaetes (Clymenella torquata, Spio setosa, and Leitoscoloplos fragilis) were used, and fluxes of oxygen and phosphate, as well as profiles of oxygen and pH in the sediment pore water, were measured. Significant differences in flux rates were found among treatments that were unrelated to polychaete abundance or biomass alone. Multispecies assemblages had lower flux rates of both oxygen and phosphate than rates calculated from the single-species treatments. Depthintegrated oxygen and pH profiles also showed significant differences between multispecies assemblages and selected single-species treatments. These differences were most likely from species-specific feeding and burrowing behavior and species-related interactions. Coefficients of variance for both oxygen and pH were highest for microcosms with no polychaetes and lowest for the assemblages, indicating a dampening effect of multispecies assemblages on porewater heterogeneity. When oxygen flux data was incorporated into a model of oxygen dynamics in Long Island Sound, results indicated that shifts in the benthic community composition could change sediment oxygen consumption rates sufficiently to disrupt the balance between the physical supply of oxygenated water and biological oxygen demand. The results of this study confirm the importance of benthic functional biodiversity to nearshore sedimentary processes and suggest that losses of functional diversity can have significant effects on ecosystem function

Injection of FGD Grout to Abate Acid Mine Drainage in Underground Coal Mines

Acid Mine Drainage (AMD) from abandoned underground coal mines in Ohio is a concern for both residents and regulatory agencies. Effluent from these mines is typically characterized by low pH and high iron and sulfate concentrations and may contaminate local drinking-water supplies and streams. The objective of this project is to demonstrate the technical feasibility of injecting cementitious alkaline materials, such as Flue Gas Desulfurization (FGD) material to mitigate current adverse environmental impacts associated with AMD in a small, abandoned deep mine in Coshocton County Ohio. The Flue Gas Desulfurization material will be provided from American Electric Power`s (AEP) Conesville Plant. It will be injected as a grout mix that will use Fixated Flue Gas Desulfurization material and water. The subject site for this study is located on the border of Coshocton and Muskingum Counties, Ohio, approximately 1.5 miles south-southwest of the town of Wills Creek. The study will be performed at an underground mine designated as Mm-127 in the Ohio Department of Natural Resources register, also known as the Roberts-Dawson Mine. The mine operated in the mid-1950s, during which approximately 2 million cubic feet of coal was removed. Effluent discharging from the abandoned mine entrances has low pH in the range of 2.8-3.0 that drains directly into Wills Creek Lake. The mine covers approximately 14.6 acres. It is estimated that 26,000 tons of FGD material will be provided from AEP`s Conesville Power Plant located approximately 3 miles northwest of the subject site

First Results from The GlueX Experiment

The GlueX experiment at Jefferson Lab ran with its first commissioning beam in late 2014 and the spring of 2015. Data were collected on both plastic and liquid hydrogen targets, and much of the detector has been commissioned. All of the detector systems are now performing at or near design specifications and events are being fully reconstructed, including exclusive production of $\pi^{0}$, $\eta$ and $\omega$ mesons. Linearly-polarized photons were successfully produced through coherent bremsstrahlung and polarization transfer to the $\rho$ has been observed.Comment: 8 pages, 6 figures, Invited contribution to the Hadron 2015 Conference, Newport News VA, September 201

Phase II trial of isoflavone in prostate-specific antigen recurrent prostate cancer after previous local therapy

<p>Abstract</p> <p>Background-</p> <p>Data exist that demonstrate isoflavones' potent antiproliferative effects on prostate cancer cells. We evaluated the efficacy of isoflavone in patients with PSA recurrent prostate cancer after prior therapy. We postulated that isoflavone therapy would slow the rate of rise of serum PSA.</p> <p>Methods-</p> <p>Twenty patients with rising PSA after prior local therapy were enrolled in this open-labeled, Phase II, nonrandomized trial (Trial registration # NCT00596895). Patients were treated with soy milk containing 47 mg of isoflavonoid per 8 oz serving three times per day for 12 months. Serum PSA, testosterone, lipids, isoflavone levels (genistein, daidzein, and equol), and quality of life (QOL) were measured at various time points from 0 to 12 months. PSA outcome was evaluated.</p> <p>Results-</p> <p>Within the mixed regression model, it was estimated that PSA had increased 56% per year before study entry and only increased 20% per year for the 12-month study period (<it>p </it>= 0.05). Specifically, the slope of PSA after study entry was significantly lower than that before study entry in 6 patients and the slope of PSA after study entry was significantly higher than before study entry in 2 patients. For the remaining 12 patients, the change in slope was statistically insignificant. Nearly two thirds of the patients were noted to have significant levels of free equol in their serum while on therapy.</p> <p>Conclusion-</p> <p>Dietary intervention with isoflavone supplementation may have biologic activity in men with biochemical recurrent prostate cancer as shown by a decline in the slope of PSA. This study may lend support to the literature that nutritional supplements have biologic activity in prostate cancer and therefore, further studies with these agents in randomized clinical trials should be encouraged.</p