Bone mineral health is sensitively related to environmental cadmium exposure- experimental and human data

Exposure to cadmium (Cd) is recognised as one of the risk factors for osteoporosis, although critical exposure levels and exact mechanisms are still unknown. Here, we first confirmed that in male Wistar rats challenged orally with 6 different levels of Cd (0.3–10 mg/kg b.w.), over 28 days, there was a direct dose relationship to bone Cd concentration. Moreover, bone mineral content was significantly diminished by ∼15% (p < 0.0001) plateauing already at the lowest exposure level. For the other essential bone elements zinc (Zn) loss was most marked. Having established the sensitive metrics (measures of Cd exposure), we then applied them to 20 randomly selected human femoral head bone samples from 16 independent subjects. Bone Cd concentration was inversely proportional to trabecular bone mineral density and mineral (calcium) content and Zn content of bone, but not the donor's age. Our findings, through direct bone analyses, support the emerging epidemiological view that bone health, adjudged by mineral density, is extremely sensitive to even background levels of environmental Cd. Importantly, however, our data also suggest that Cd may play an even greater role in compromised bone health than prior indirect estimates of exposure could reveal. Environmental Cd may be a substantially determining factor in osteoporosis and large cohort studies with direct bone analyses are now merited

Bioavailability of Echinacea Constituents: Caco-2 Monolayers and Pharmacokinetics and the Alkylamides and Caffeic Acid Conjugates

Many studies have been done over the years to assess the effectiveness of Echinacea as an immunomodulator. We have assessed the potential bioavailability of alkylamides and caffeic acid conjugates using Caco-2 monolayers and compared it to their actualbioavailability in a Phase I clinical trial. The caffeic acid conjugates permeated poorly through the Caco-2 monolayers. Alkylamides were found to diffuse rapidly through Caco-2 monolayers. Differences in diffusion rates for each alkylamide correlated to structural variations, with saturation and N-terminal methylation contributing to decreases in diffusion rates. Alkylamide diffusion is not affected by the presence of other constituents and the results for a synthetic alkylamide were in line with those for alkylamides found in an ethanolic Echinacea preparation. We examined plasma from healthy volunteers for 12 hours after ingestion of Echinacea tablets manufactured from an ethanolic liquid extract. Caffeic acid conjugates could not be identified in any plasma sample at any time after tablet ingestion. Alkylamides were detected in plasma 20 minutes after tablet ingestion and for each alkylamide, pharmacokinetic profiles were devised. The data are consistent with the dosing regimen of one tablet three times daily and supports their usage as the primary markers for quality Echinacea preparations

Growth and yield of mixed versus pure stands of Scots pine (Pinus sylvestris L. ) and European beech (Fagus sylvatica L.) analysed along a productivity gradient through Europe

Mixing of complementary tree species may increase stand productivity, mitigate the effects of drought and other risks, and pave the way to forest production systems which may be more resource-use efficient and stable in the face of climate change. However, systematic empirical studies on mixing effects are still missing for many commercially important and widespread species combinations. Here we studied the growth of Scots pine (Pinus sylvestris L.) and European beech (Fagus sylvatica L.) in mixed versus pure stands on 32 triplets located along a productivity gradient through Europe, reaching from Sweden to Bulgaria and from Spain to the Ukraine. Stand inventory and taking increment cores on the mainly 60-80 year-old trees and 0.02-1.55 ha sized, fully stocked plots provided insight how species mixing modifies the structure, dynamics and productivity compared with neighbouring pure stands. In mixture standing volume (+12 %), stand density (+20 %), basal area growth (+12 %), and stand volume growth (+8 %) were higher than the weighted mean of the neighbouring pure stands. Scots pine and European beech contributed rather equally to the overyielding and overdensity. In mixed stands mean diameter (+20 %) and height (+6 %) of Scots pine was ahead, while both diameter and height growth of European beech were behind (−8 %). The overyielding and overdensity were independent of the site index, the stand growth and yield, and climatic variables despite the wide variation in precipitation (520-1175 mm year−1), mean annual temperature (6-10.5 °C), and the drought index by de Martonne (28-61 mm °C−1) on the sites. Therefore, this species combination is potentially useful for increasing productivity across a wide range of site and climatic conditions. Given the significant overyielding of stand basal area growth but the absence of any relationship with site index and climatic variables, we hypothesize that the overyielding and overdensity results from several different types of interactions (light-, water-, and nutrient-related) that are all important in different circumstances. We discuss the relevance of the results for ecological theory and for the ongoing silvicultural transition from pure to mixed stands and their adaptation to climate change.The networking in this study has been sup-ported by COST Action FP1206 EuMIXFOR. All contributors thanktheir national funding institutions to establish, measure, and analysedata from the triplets. The first author also thanks the BayerischenStaatsforsten (BaySF) for supporting the establishment of the plots,the Bavarian State Ministry for Nutrition, Agriculture, and Forestryfor permanent support of the project W 07 ‘‘Long-term experimentalplots for forest growth and yield research’’ (# 7831-22209-2013) andthe German Science Foundation for providing the funds for the pro-jects PR 292/12-1 ‘‘Tree and stand-level growth reactions on droughtin mixed versus pure forests of Norway spruce and European beech’’.Thanks are also due to Ulrich Kern for the graphical artwork, and totwo anonymous reviewers for their constructive criticism

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Semisynthesis of Taxol®: an improved procedure for the isolation of 10-deacetylbaccatin III

From the needles of domestic yew, (Taxus baccata), 10-deacetylbaccatin III (10-DAB) can be isolated in quantities of up to 297 mg per kg of fresh needles. Additional quantities of 10-DAB can be obtained from the extract by NaBH4 mediated reductive hydrolysis of baccatin esters. A four-step procedure converts 10-DAB into taxol in 58% overall yield

Influence of diatomite microstructure on its adsorption capacity for Pb(II)

The effect of microstructural changes caused by mechanical modification on adsorption properties of diatomite samples were investigated The microstructure has been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and atomic force microscopy (AFM) while the degree of metal adsorption was evaluated by Inductively Coupled Plasma Atomic Emission Spectrometry (ICP AES). The results show that metal sorption capacity of diatomite is considerably improved after mechanical modification and it can be attributed to amorphysation of the material. Immobilization efficiency increased from 22% for untreated to 81% for the treated sample after 5h at BPR 4. This qualifies natural diatomite as a material for wastewater remediation