Effect of chirality of small molecule organofluorine inhibitors of amyloid self-assembly on inhibitor potency

The effect of enantiomeric trifluoromethyl-indolyl-acetic acid ethyl esters on the fibrillogenesis of Alzheimer’s amyloid β (Aβ) peptide is described. These compounds have been previously identified as effective inhibitors of the Aβ self-assembly in their racemic form. Thioflavin-T Fluorescence Spectroscopy and Atomic Force Microscopy were applied to assess the potency of the chiral target compounds. Both enantiomers showed significant inhibition in the in vitro assays. The potency of the enantiomeric inhibitors appeared to be very similar to each other suggesting the lack of the stereospecific binding interactions between these small molecule inhibitors and the Aβ peptide.     

ER stress contributes to renal proximal tubule injury by increasing SREBP-2-mediated lipid accumulation and apoptotic cell death

Renal proximal tubule injury is induced by agents/conditions known to cause endoplasmic reticulum (ER) stress, including cyclosporine A (CsA), an immunosuppressant drug with nephrotoxic effects. However, the underlying mechanism by which ER stress contributes to proximal tubule cell injury is not well understood. In this study, we report lipid accumulation, sterol regulatory element-binding protein-2 (SREBP-2) expression, and ER stress in proximal tubules of kidneys from mice treated with the classic ER stressor tunicamycin (Tm) or in human renal biopsy specimens showing CsA-induced nephrotoxicity. Colocalization of ER stress markers [78-kDa glucose regulated protein (GRP78), CHOP] with SREBP-2 expression and lipid accumulation was prominent within the proximal tubule cells exposed to Tm or CsA. Prolonged ER stress resulted in increased apoptotic cell death of lipid-enriched proximal tubule cells with colocalization of GRP78, SREBP-2, and Ca(2+)-independent phospholipase A(2) (iPLA(2)β), an SREBP-2 inducible gene with proapoptotic characteristics. In cultured HK-2 human proximal tubule cells, CsA- and Tm-induced ER stress caused lipid accumulation and SREBP-2 activation. Furthermore, overexpression of SREBP-2 or activation of endogenous SREBP-2 in HK-2 cells stimulated apoptosis. Inhibition of SREBP-2 activation with the site-1-serine protease inhibitor AEBSF prevented ER stress-induced lipid accumulation and apoptosis. Overexpression of the ER-resident chaperone GRP78 attenuated ER stress and inhibited CsA-induced SREBP-2 expression and lipid accumulation. In summary, our findings suggest that ER stress-induced SREBP-2 activation contributes to renal proximal tubule cell injury by dysregulating lipid homeostasis.     

Building a Comprehensive Mill-Level Database for the Industrial Sectors Integrated Solutions (ISIS) Model of the U.S. Pulp and Paper Sector

Air emissions from the U.S. pulp and paper sector have been federally regulated since 1978; however, regulations are periodically reviewed and revised to improve efficiency and effectiveness of existing emission standards. The Industrial Sectors Integrated Solutions (ISIS) model for the pulp and paper sector is currently under development at the U.S. Environmental Protection Agency (EPA), and can be utilized to facilitate multi-pollutant, sector-based analyses that are performed in conjunction with regulatory development. The model utilizes a multi-sector, multi-product dynamic linear modeling framework that evaluates the economic impact of emission reduction strategies for multiple air pollutants. The ISIS model considers facility-level economic, environmental, and technical parameters, as well as sector-level market data, to estimate the impacts of environmental regulations on the pulp and paper industry. Specifically, the model can be used to estimate U.S. and global market impacts of new or more stringent air regulations, such as impacts on product price, exports and imports, market demands, capital investment, and mill closures. One major challenge to developing a representative model is the need for an extensive amount of data. This article discusses the collection and processing of data for use in the model, as well as the methods used for building the ISIS pulp and paper database that facilitates the required analyses to support the air quality management of the pulp and paper sector.     

The occurrence of caulonema-specific proteins in different moss species

Soluble proteins extracted with Tris-buffer pH 8.8 from different mosses are analysed by microgelelectrophoretic method for comparison to the specific proteins present only in the caulonema of Funaria hygrometrica. The protein patterns are also compared with those of liverwort, fern gametophytes and sporophytes and tobacco. It is observed that the caulonema specific proteins are only present in the caulonema of these mosses and are absent in other plants.Abbreviations CSP caulonema specific proteins     

Direct rooting and hardening of tea microshoots in the field

Micropropagation of tea (Camellia sinensis (L.) O. Kuntze) has been widely attempted but commercial exploitation of this method is limited by heavy losses during the hardening procedures. In the present study, optimization of time of harvesting (spring and early summer) of microshoots, shoot size, soil pH (4.0–6.4), plant growth regulator treatment (IBA; 500 mg l^-1, 30 min) CO₂ (9.09/10×10⁻⁵ mol l^-1 to 10.22/10×10^-5 mol l^-1 and 20/11×10⁻⁵ mol l^-1 to 80/13×10⁻⁷ mol l^-1) enrichment and light (15 μ mol m^-2 s^-1) conditions in specially designed hardening chambers, made a significant impact on the percent of success for hardening. Following the standardized procedure, up to 71.6% root induction and 73% survival could be achieved. Successful field transfer was also accomplished. This revised version was published online in June 2006 with corrections to the Cover Date.     

Selective cytotoxicity of Pancratistatin-related natural <Emphasis Type="Italic">Amaryllidaceae</Emphasis> alkaloids: evaluation of the activity of two new compounds

Background  

Pancratistatin (PST), a compound extracted from an Amaryllidaceae (AMD) family plant, has been shown to specifically induce apoptosis in cancer cells with no/minimal toxic effect on normal cells. A systematic synthetic approach has indicated that the minimum cytotoxic pharmacophore comprises the trans-fused b/c-ring system containing the 2, 3, 4-triol unit in the C-ring. To further explore the structure-activity relationship of this group of compounds we have investigated the anti-cancer efficacy and specificity of two PST-related natural compounds, AMD4 and AMD5. Both of these compounds lack the polyhydroxylated lycorane element of PST instead having a methoxy-substuituted crinane skeleton.