Molecular Mechanisms of Pharmaceutical Drug Binding into Calsequestrin

Calsequestrin (CASQ) is a major Ca²⁺-storage/buffer protein present in the sarcoplasmic reticulum of both skeletal (CASQ1) and cardiac (CASQ2) muscles. CASQ has significant affinity for a number of pharmaceutical drugs with known muscular toxicities. Our approach, with in silico molecular docking, single crystal X-ray diffraction, and isothermal titration calorimetry (ITC), identified three distinct binding pockets on the surface of CASQ2, which overlap with 2-methyl-2,4-pentanediol (MPD) binding sites observed in the crystal structure. Those three receptor sites based on canine CASQ1 crystal structure gave a high correlation (R² = 0.80) to our ITC data. Daunomycin, doxorubicin, thioridazine, and trifluoperazine showed strong affinity to the S1 site, which is a central cavity formed between three domains of CASQ2. Some of the moderate-affinity drugs and some high-affinity drugs like amlodipine and verapamil displayed their binding into S2 sites, which are the thioredoxin-like fold present in each CASQ domain. Docking predictions combined with dissociation constants imply that presence of large aromatic cores and less flexible functional groups determines the strength of binding affinity to CASQ. In addition, the predicted binding pockets for both caffeine and epigallocatechin overlapped with the S1 and S2 sites, suggesting competitive inhibition by these natural compounds as a plausible explanation for their antagonistic effects on cardiotoxic side effects.     

Metal pollution and selenium distributions in soils and grass near a non-ferrous plant

Multi-element analysis results of direct energy-dispersive X-ray fluorescence of soil samples taken in the vicinity of a non-ferrous plant in Antwerp are reported. High concentrations of Pb, Cu, Zn, As and Se are found in nearby residential areas, especially in top-soil layers. Selenium pollution appears not to be leached significantly to lower soil horizons, but it is available for uptake by rye-grass, in which toxic levels are found. Results are compared to literature data. Hydride generation atomic absorption spectrometry proved to be unsuitable for direct analysis of the heavily contaminated soils.     

Gas phase sorting of fullerenes, polypeptides and carbon nanotubes

We discuss the Stark deflectometry of micro-modulated molecular beams for the enrichment of biomolecular isomers as well as single-wall carbon nanotubes, and we demonstrate the working principle of this idea with fullerenes. The sorting is based on the species-dependent susceptibility-to-mass ratio χ/m. The device is compatible with a high molecular throughput, and the spatial micro-modulation of the beam permits one to obtain a fine spatial resolution and a high sorting sensitivity.     

Determination of inlet transmission and conversion efficiencies for in situ measurements of the nocturnal nitrogen oxides, NO3, N2O5 and NO2, via pulsed cavity ring-down spectroscopy

Pulsed cavity ring-down spectroscopy is a highly sensitive method for direct absorption spectroscopy that has been applied to in situ detection of NO3, N2O5 and NO2 in the atmosphere from a variety of platforms, including ships, aircraft, and towers. In this paper, we report the development of schemes to significantly improve the accuracy of these measurements. This includes the following: (1) an overall improvement in the inlet transmission efficiencies (92 +/- 2% for NO3 and 97 +/- 1% for N2O5) achieved primarily through a reduction in the inlet residence time; and (2) the development of a calibration procedure that allows regular determination of these efficiencies in the field by addition of NO3 or N2O5 to the inlet from a portable source followed by conversion of NO3 to NO2. In addition, the dependence of the instrument's sensitivity and accuracy to a variety of conditions encountered in the field, including variations in relative humidity, aerosol loading, and VOC levels, was systematically investigated. The rate of degradation of N2O5 transmission efficiency on the inlet and filter system due to the accumulation of inorganic aerosol was determined, such that the frequency of filter changes required for accurate measurements could be defined. In the absence of aerosol, the presence of varying levels of relative humidity and reactive VOC were found to be unimportant factors in the instrument's performance. The 1 sigma accuracy of the NO3, N2O5, and NO2 measured with this instrument are -9/+12, -8/+11, +/- 6%, respectively, where the -/+ signs indicate that the actual value is low/high relative to the measurement. The largest contribution to the overall uncertainty is now due to the NO3 absorption cross section rather than the inlet transmission efficiency.     

Universally applicable model for the quantitative determination of lake sediment composition using fourier transform infrared spectroscopy

Fourier transform infrared spectroscopy (FTIRS) can provide detailed information on organic and minerogenic constituents of sediment records. Based on a large number of sediment samples of varying age (0-340,000 yrs) and from very diverse lake settings in Antarctica, Argentina, Canada, Macedonia/Albania, Siberia, and Sweden, we have developed universally applicable calibration models for the quantitative determination of biogenic silica (BSi; n = 816), total inorganic carbon (TIC; n = 879), and total organic carbon (TOC; n = 3164) using FTIRS. These models are based on the differential absorbance of infrared radiation at specific wavelengths with varying concentrations of individual parameters, due to molecular vibrations associated with each parameter. The calibration models have low prediction errors and the predicted values are highly correlated with conventionally measured values (R = 0.94-0.99). Robustness tests indicate the accuracy of the newly developed FTIRS calibration models is similar to that of conventional geochemical analyses. Consequently FTIRS offers a useful and rapid alternative to conventional analyses for the quantitative determination of BSi, TIC, and TOC. The rapidity, cost-effectiveness, and small sample size required enables FTIRS determination of geochemical properties to be undertaken at higher resolutions than would otherwise be possible with the same resource allocation, thus providing crucial sedimentological information for climatic and environmental reconstructions.     

Dietary selenium intake in Belgium for different population groups at risk for deficiency

An estimation of the dietary selenium intake in different population groups in Belgium has been carried out. 24 h duplicate meals and food consumption statistics combined with concentration levels in different foods, as determined by hydride generation atomic absorption spectrometry, are used. Dietary intake of selenium is low to very low, especially for vegetarians (12.7 +/- 9.1 micrograms) and patients on long-term total parenteral nutrition (1.2 +/- 0.8 microgram). The different intakes are discussed and compared with intakes published for other countries, while the importance of bioavailability of the selenium in food in the risk of deficiency is stressed.     

Selenium content of goat milk and its distribution in protein fractions

Summary This study reports on selenium distribution in goat milk. Skim milk was found to contain the major part (94%) of total milk selenium. The selenium distribution over casein and whey protein fractions depends on the separation method used, but irrespective of these methods, skim milk selenium is mainly associated with the casein fraction (> 69%). Approximately 9%, 7% and 24% of selenium is removed by dialysis (molecular cutoff 10–12 kDa) from skim milk, casein and whey respectively, indicating a major association of selenium with milk proteins. This observation is confirmed by selenium analysis of individual caseins and whey proteins isolated through ion-exchange chromatography and gel filtration. Selenium concentrations of the different isolated milk proteins show considerable variation (caseins: 294–550 ng Se/g; whey proteins: 217–457 ng Se/g).

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Der Selengehalt von Ziegenmilch und seine Verteilung in den Proteinfraktionen

Zusammenfassung Diese Studie bespricht die Selen-Verteilung in Ziegenmilch. Magermilch enthält 94% des gesamten Selens der Milch. Die Selen-Verteilung ist abhängig von der Technik des Abtrennens des Caseins von den Molkenproteinen, aber ungeachtet dessen befindet sich das Selen der Magermilch hauptsächlich in der Casein-Fraktion (>69%). Ungefähr 9% bzw. 7% bzw. 24% des Selens wurden aus Magermilch bzw. Casein bzw. Molke durch Dialyse (molekulare Ausschaltung 10–12 kDa) entfernt, was auf eine Assoziation des Selens mit den Milchproteinen hinweist. Dies wurde bestätigt durch die Selenanalyse des durch Ionenaustauschchromatographie bzw. Gelfiltration isolierten Caseins und der Molkeproteine. Der Selengehalt der verschiedenen isolierten Milchproteine zeigt bemerkenswerte Differenzen (Caseine: 294–550 ng Se/g; Molkeproteinen: 217–457 ng Se/g).

     

Coloring Properties of Various High‐Nitrogen Compounds in Pyrotechnic Compositions

Strontium salts are widely used in red flame pyrotechnic compositions, usually combined with perchlorate salts as oxidizer. The potential environmental impact of perchlorate could be avoided by using high‐nitrogen compounds. Therefore, the following nitrogen‐rich strontium salts were prepared and characterized: strontium tetrazolate pentahydrate ( 1 ), strontium 1‐methyl‐5‐nitriminotetrazolate monohydrate ( 2 ), and strontium 1‐(2‐chloroethyl)‐5‐nitriminotetrazolate monohydrate ( 3 ). Their combustion behavior and both color intensity and purity were investigated in pyrotechnics. These results were compared with the US Army in‐service signal formulation.     

Quantitative analysis of deuterium using laser-induced plasma at low pressure of helium

It was proved that the analysis of deuterium can be conducted using laser-induced plasma spectroscopy. By selecting the appropriate surrounding gas, its pressure, and gating time of the detection system, it was shown that the emission lines of both hydrogen (H(alpha)) and deuterium (D(alpha)), separated by only 0.179 nm, can be fully resolved. A linear calibration curve was also obtained, indicating that this technique has the potential for quantitative analysis of deuterium. The minimum detection limit achieved in this stage of research was estimated to be 50 ppm. We have also shown that this technique can be used as a simple and rapid method for D and H analysis in solid samples.